Zola IK (1973) Pathways to the doctor- from person to patient. *Social science medicine*, 677-689

potential demonstration of nerve root decompression after VAX-D Therapy.

back pain with a visual analogue scale and a semantic differential scale.

variables on the treatment of pain in Eastern Part of Nigeria – Epidemiological Study', 10th World Congress on Pain, August 17 – 22, Sandiego, California,79. Steele MF, Spurgeon JB (1983) Body size, Body form and Nutritional intake of Blacks Ages 9

Living in Rural and Urban Regions of Eastern North Carolina. Growth 47, 207-216.

Merskey H, Bogduk N (1994) Classification of chronic pain. IASP press, Seattle; 189 – 200. Naguszewski WK, Naguszewski RK, Crose EE. Dermatomal Somatosensory evoked

Research. Seattle, IASP Press 25.

Switzerland.

Press 11.

Neurological Researcch 2001; 23, 706-714, 2001

Physiotherapy Theory and Practice 20, 135-142.

Low back pain (LBP) is the most prevalent and expensive musculoskeletal problem worldwide. As many as eight in every ten adults experience LBP at some point in their lifetime (Dionne et al., 2001). An episode of LBP usually lasts a few days in most people, unfortunately in some individuals, the pain deteriorates and persists for an extended period of time; to a point where it considerably limits daily activities including work and leisure (Truchon & Fillion, 2000). Substantial economic burden is incurred due to sickness absence, with loss of productivity and healthcare costs relating to treatment for these chronic or recurrent LBP patients. It was estimated that the total healthcare expenses incurred by LBP patients costs \$91 billion in the US (Luo et al., 2004).

LBP is a complex multifactorial phenomenon. The complexity of LBP may be viewed as the multiple biomechanical, psychosocial and individual factors which are closely-interacting with each other (National Institute of Occupational Safety and Health, 1997). Although the etiologic mechanisms for LBP are still poorly understood, many reviews and studies have concluded that the ergonomic work factors are most common LBP risk factors. They include lifting, forceful movement, whole body vibration, and awkward postures (Cohen et al., 2010, Vandergrift et al., 2012; Punnett et al., 2005). Increasing evidence exists that suggests psychosocial phenomena are also linked to low back problems, although to date the evidence for these is less conclusive. Understanding the importance of the psychosocial pathway in the development of LBP lies not only in the advancement of knowledge in the phenomenon, but also in designing preventive interventions. Five plausible explanations have been suggested to account for associations between work-related psychosocial factors and musculoskeletal symptoms (National Institute of Occupational Safety and Health, 1997).

#### **2. Psychosocial factor**

A psychosocial factor "may be defined as a measurement that potentially relates psychological phenomena to the social environment and to the pathophysiological changes" (Hemingway & Marmot, 1999). The concept of psychosocial factors includes a vast array of conditions that fall within three separate domains (National Institute of Occupational Safety and Health, 1997): (1) factors associated with the job and work environment, (2) factors associated with outside of work environment (3) characteristics of the individual.

Psychosocial Risk Factors in the Development of LBP 81

On the contrary, Hartivigsen et al. (2004), after critically assessing 40 epidemiological literature published between 1990 and 2002, found moderate to strong evidence for no association between LBP and consequences of LBP and perception of work, organizational aspects of work, social support and stress at work. The major strengths in this review are the inclusion of prospective cohort studies and that both the level and the strength of evidence are reported. Similarly, a recent study by Clays et al. (2007), in a longitudinal study of 2556 middle-aged workers, found a non-significant association between LBP and low decision latitude, high job insecurity, feeling stressed at work after adjusted individual and physical risks. The major flaw in this study is a large drop out rate, which may probably

Despite the findings were inconsistent, some authors (Bongers et al., 1993; National Institute of Occupational Safety and Health, 1997) suggest that intensified workload, monotonous work, low job satisfaction, low social support, low job control, and job stress may be associated with LBP or low back disorders. However, the possible effect of gender has not been evaluated in most of these epidemiological studies. There are only few reviews and studies that have analyzed female group and male group separately or have investigated the

In a cross-sectional study by Josephson et al. (1998) of 269 female nursing personnel, found insufficient social support had the highest risk for care seeking behavior for low back pain, as assessed by physical examination and blinded interviews after confounder adjustments for age and smoking. Barnekow-Bergkvist (1998) defined, in a 18-year study of 425 Swedish students, an outcome as self-report of low back symptoms. The students had psychosocial assessment which included psychosocial stress at work, sociodemographic factors and stress, and individual attributes. Among the women, low back problems were related to monotonous work. The strength of this study is that it analyzed the influence of physical workload, psychosocial stress, and sociodemographic and individual factors together. However, those who worked less than 16 hours/week were excluded (women > men), the results of the analyses of associations between work-related risk factors and low back

In contrast, Vingard et al. (2000), in a study of 1193 working women and 925 working men, found monotonous work and low job satisfaction had very limited influence in women when compared to men, after adjustment for lifestyle, and physical loads in leisure time and sport activities. They explained that possibly women are more satisfied with their work situation or have lower expectations than men. In a similar vein, Hofftman et al. (2004) reviewed 14 studies regarding gender differences in the effect of risk factors on back complaints and found that psychosocial work factors are shown to be important, but to a

In a recent systematic review, Ramond et al. (2011) examined 23 prospective studies to review the evidence for psychosocial risk factors and LBP outcome in primary care, in which 16 psychosocial factors were included in the analysis. The review found that social support was not associated with LBP whilst job satisfaction was mostly not associated with LBP, and LBP requiring compensation was shown to be a predictive factor for negative LBP outcome. A longitudinal study by Vandergrift et al. (2012) investigated the relationship between physical and psychosocial risk factors for LBP among 1181 workers of automobile

lead to selection bias.

psychosocial risk factors among women only.

problem of women may be underestimated.

lesser extent in women when compared to men.

Included in the domain of job and work environment include various aspects of job content, for example, perceived workload, monotonous work, low job control, low job satisfaction, limited social support (Truchon, 2001). Outside of work environment parameters typically include factors associated with demands and responsibilities in family situation and leisure time, and social/familial relationship and support. Finally, individual factors are generally of two types corresponding to: (1) sociodemographic factors, for example, age, social class, culture, educational status; life style (smoking) and (2) psychological factors, for example, affective variables (anxiety and depression), personality traits, cognitive variables (fear avoidance and life satisfaction) and coping strategies (catastrophizing) (Pincus et al., 2002a; Truchon, 2001).

It is important to note, however, that the linkages between psychosocial factors and LBP are complex and influenced by a multitude of conditions. Psychosocial factors may exert effect alone or combine in clusters, and may act at different stages of LBP. In particular, both personal and situational characteristics may lead to differences in the way individuals exposed to the same situation may perceive and/or react to the situation (Burton & Erg, 1997; National Institute of Occupational Safety and Health, 1997).

#### **2.1 Psychosocial work characteristics**

Psychosocial factors related to job and work environment are characterized by high perceived workload, monotonous work, low job control, low job satisfaction, and limited social support. A number of reviews have shown varying levels of associations between measures of work-related psychosocial factors and self-reported back pain (Bongers et al., 1993; Davis & Heaney, 2000; Hartvigsen et al., 2004; Hoogendoorn et al., 2000; National Institute of Occupational Safety and Health, 1997; Ramond et al., 2011).

Bongers et al. (1993) reviewed 46 articles published between 1973 and 1992, in which some evidence for an association between low back disorders and monotonous work was found. Evidence shows that there is a contradictory relationship between low back disorders and work demands while the evidence for a relationship between poor social support and low back disorders is mixed. In a similar vein, among the 13 studies published between 1973 and 1994 reviewed by NIOSH (National Institute of Occupational Safety and Health, 1997) found mixed evidence for an association between monotonous work and back disorders and contradicting evidence for an association between back disorders and job dissatisfaction. Weak evidence is found in the association between social support and back disorders while the relationship between low job control and back disorders has limited evidence. However, significant association was found between back disorders and perceptions of intensified workload (National Institute of Occupational Safety and Health, 1997). It is important to note that potential covariates were controlled in most studies that have been reviewed by NIOSH. Davis & Heaney (2000) reviewed 66 articles that were published before 1999. They concluded that there seems to be a consistent relationship between low job satisfaction and job stress with the development of LBP in those better quality studies. Likewise, Hoogendoorn et al. (2000), after reviewing 11 cohort and two case-control studies, concluded that there was strong evidence for low job satisfaction and low social support in the workplace as risk factor for back pain.

Included in the domain of job and work environment include various aspects of job content, for example, perceived workload, monotonous work, low job control, low job satisfaction, limited social support (Truchon, 2001). Outside of work environment parameters typically include factors associated with demands and responsibilities in family situation and leisure time, and social/familial relationship and support. Finally, individual factors are generally of two types corresponding to: (1) sociodemographic factors, for example, age, social class, culture, educational status; life style (smoking) and (2) psychological factors, for example, affective variables (anxiety and depression), personality traits, cognitive variables (fear avoidance and life satisfaction) and coping strategies (catastrophizing) (Pincus et al., 2002a;

It is important to note, however, that the linkages between psychosocial factors and LBP are complex and influenced by a multitude of conditions. Psychosocial factors may exert effect alone or combine in clusters, and may act at different stages of LBP. In particular, both personal and situational characteristics may lead to differences in the way individuals exposed to the same situation may perceive and/or react to the situation (Burton & Erg,

Psychosocial factors related to job and work environment are characterized by high perceived workload, monotonous work, low job control, low job satisfaction, and limited social support. A number of reviews have shown varying levels of associations between measures of work-related psychosocial factors and self-reported back pain (Bongers et al., 1993; Davis & Heaney, 2000; Hartvigsen et al., 2004; Hoogendoorn et al., 2000; National

Bongers et al. (1993) reviewed 46 articles published between 1973 and 1992, in which some evidence for an association between low back disorders and monotonous work was found. Evidence shows that there is a contradictory relationship between low back disorders and work demands while the evidence for a relationship between poor social support and low back disorders is mixed. In a similar vein, among the 13 studies published between 1973 and 1994 reviewed by NIOSH (National Institute of Occupational Safety and Health, 1997) found mixed evidence for an association between monotonous work and back disorders and contradicting evidence for an association between back disorders and job dissatisfaction. Weak evidence is found in the association between social support and back disorders while the relationship between low job control and back disorders has limited evidence. However, significant association was found between back disorders and perceptions of intensified workload (National Institute of Occupational Safety and Health, 1997). It is important to note that potential covariates were controlled in most studies that have been reviewed by NIOSH. Davis & Heaney (2000) reviewed 66 articles that were published before 1999. They concluded that there seems to be a consistent relationship between low job satisfaction and job stress with the development of LBP in those better quality studies. Likewise, Hoogendoorn et al. (2000), after reviewing 11 cohort and two case-control studies, concluded that there was strong evidence for low job satisfaction and low social support in

1997; National Institute of Occupational Safety and Health, 1997).

Institute of Occupational Safety and Health, 1997; Ramond et al., 2011).

**2.1 Psychosocial work characteristics**

the workplace as risk factor for back pain.

Truchon, 2001).

On the contrary, Hartivigsen et al. (2004), after critically assessing 40 epidemiological literature published between 1990 and 2002, found moderate to strong evidence for no association between LBP and consequences of LBP and perception of work, organizational aspects of work, social support and stress at work. The major strengths in this review are the inclusion of prospective cohort studies and that both the level and the strength of evidence are reported. Similarly, a recent study by Clays et al. (2007), in a longitudinal study of 2556 middle-aged workers, found a non-significant association between LBP and low decision latitude, high job insecurity, feeling stressed at work after adjusted individual and physical risks. The major flaw in this study is a large drop out rate, which may probably lead to selection bias.

Despite the findings were inconsistent, some authors (Bongers et al., 1993; National Institute of Occupational Safety and Health, 1997) suggest that intensified workload, monotonous work, low job satisfaction, low social support, low job control, and job stress may be associated with LBP or low back disorders. However, the possible effect of gender has not been evaluated in most of these epidemiological studies. There are only few reviews and studies that have analyzed female group and male group separately or have investigated the psychosocial risk factors among women only.

In a cross-sectional study by Josephson et al. (1998) of 269 female nursing personnel, found insufficient social support had the highest risk for care seeking behavior for low back pain, as assessed by physical examination and blinded interviews after confounder adjustments for age and smoking. Barnekow-Bergkvist (1998) defined, in a 18-year study of 425 Swedish students, an outcome as self-report of low back symptoms. The students had psychosocial assessment which included psychosocial stress at work, sociodemographic factors and stress, and individual attributes. Among the women, low back problems were related to monotonous work. The strength of this study is that it analyzed the influence of physical workload, psychosocial stress, and sociodemographic and individual factors together. However, those who worked less than 16 hours/week were excluded (women > men), the results of the analyses of associations between work-related risk factors and low back problem of women may be underestimated.

In contrast, Vingard et al. (2000), in a study of 1193 working women and 925 working men, found monotonous work and low job satisfaction had very limited influence in women when compared to men, after adjustment for lifestyle, and physical loads in leisure time and sport activities. They explained that possibly women are more satisfied with their work situation or have lower expectations than men. In a similar vein, Hofftman et al. (2004) reviewed 14 studies regarding gender differences in the effect of risk factors on back complaints and found that psychosocial work factors are shown to be important, but to a lesser extent in women when compared to men.

In a recent systematic review, Ramond et al. (2011) examined 23 prospective studies to review the evidence for psychosocial risk factors and LBP outcome in primary care, in which 16 psychosocial factors were included in the analysis. The review found that social support was not associated with LBP whilst job satisfaction was mostly not associated with LBP, and LBP requiring compensation was shown to be a predictive factor for negative LBP outcome. A longitudinal study by Vandergrift et al. (2012) investigated the relationship between physical and psychosocial risk factors for LBP among 1181 workers of automobile

Psychosocial Risk Factors in the Development of LBP 83

A previous pain/injury history to the lower back is consistently a strong risk factor for future reports of LBP in the work environment (Dempsey et al., 1997; National Institute of Occupational Safety and Health, 1997). In women during/after pregnancy, there is strong evidence for the risk of developing LBP in those who had previous LBP and previous

Age has been suggested to play a role in the development of LBP in a review by Dempsey et al. (1997). The review found that the occurrence of LBP increases with increasing age up to about 50 to 60 years of age in several community-based studies, after which there seems to be a decline. Several biological plausibility of the role of age in LBP exist, in that accumulated work-related spinal damage including microtruama, natural degeneration of the spine, and decreased spinal load bearing capacity. With regards to LBP during pregnancy, Wu et al.'s review (2004) found the evidence for maternal age was conflicting. In the review, nine studies suggested a higher risk in younger women, two studies suggested a

The risk of LBP is higher among women as consistently shown in community-based surveys, with odds ratios varying between 1.30 to 1.57 (Houtman et al., 1994; Skovron et al., 1994). The risk of back pain increases by twofold for women with back pain history and increases for women who have been pregnant before (Ostgaard & Andersson, 1991). Women are expected to suffer from more lower back pain because of their wider pelvis, the stress of hormonal changes, and childbirth (Meisler, 2003). Retrospective studies showed that 10-25% of women with chronic LBP report the first symptom of back pain during pregnancy (Biering-Sorensen, 1983; Svensson et al., 1990). During pregnancy, 50%-80% of women experience some degree of pregnancy-related low back pain (PLBP) and pelvic girdle pain (PPGP). Women who have previously had pelvic pain during pregnancy experience a relapse during 85% of a subsequent pregnancy (Mens et al., 1996). The pain symptoms often impact on daily activities, sleep and sometimes lead to work absenteeism and even chronic disability. A study shows lower quality of life during pregnancy among women with back problems (Olsson & Nilsson-Wikmar, 2004). Among these women who are affected by LBP, pain sometimes becomes chronic or recurrent (Larsen et al., 1999;

It was found that low back symptoms were consistently more common among the women in the highest socioeconomic class (professionals, managers, and salaried employees) (Barnekow-Bergkvist et al., 1998). Likewise, Papageorogiou et al. (1997) found significant associations between LBP and higher social class and perceived inadequacy of income in a prospective population-based cohort study of 1412 working adults, the association was more marked in women. It was argued that higher stress levels among women in high and middle socioeconomic classes because of the combination of work-related stress and stress

**2.3.1 History of previous low back pain/disorder**

higher risk for older women, and 12 had no effect.

**2.3.2 Age**

**2.3.3 Gender**

Ostgaard et al., 1997).

**2.3.4 Socioeconomic characteristics**

related to responsibilities for the family (Lundberg, 1999).

lumbopelvic pain during or after pregnancy (Wu et al., 2004).

manufacturing company. An association was found between the psychosocial risk factors of low job control and high job demand and the development of LBP only in workers with high physical exposures.

#### **2.2 Psychosocial role (outside of work)**

The main focus in the relationship between psychosocial factors and LBP has chiefly been work related in most studies. However, there is increasing awareness that psychosocial factors which are unrelated to work, may also play an important role in the development of LBP. These psychosocial factors are characterized by family or social or emotional support, leisure time activity or social contact and participation, spousal relationship and housework satisfaction. Only a few prospective studies have addressed individual and outside of work environmental psychosocial factors.

Yip et al. (2004), studying 417 middle-aged women in a case control study, found an association between psychosocial stress related to housework and LBP after adjusted for working status and source of recruitment. However, no association was found between self reported poor relationship with cohabitants, housework satisfaction, living alone and the risk of LBP. Likewise, a cross sectional longitudinal study by Barnekow-Bergkvist (1998) described earlier found no association between physical activity at leisure time and low back symptoms.

Simiarly, Hoogendoorn et al.'s review (2000), as described above, also included assessment of psychosocial factors in private life such as family support, presence of a close friend or neighbour, social contact, social participation, emotional support and concluded that insufficient evidence was found for an effect of psychosocial factors in private life because the data were very limited.

However, Brulin et al. (1998) conducted a cross sectional study of 361 women in a Swedish home care service and found having children at home decreased the risk of low back complaints (OR 0.5), even after age adjusted. It was argued that having children in the family can protect against social isolation, and that social isolation was found to increase the risk of low back pain (Frymoyer & Cats-Baril, 1987). The strength of this study lies in its combined focus on sociodemographic, physical and psychosocial factors at work and physical activity during leisure time. This study is based on a single occupation therefore the sample may not be representative of the general population. Likewise, Thorbjornsson et al. (1998), in a longitudinal study over 24 years, found that social relationship satisfaction has a long-term effect on LBP among 252 women and 232men.

#### **2.3 Individual characteristics**

Since the complexity of LBP may be represented by the interactive effect of psychosocial, biomechanical and individual factors (Chany et al., 2006), a better understanding in individual factors may elucidate the complex reactions. These individual factors are characterized by history of previous low back pain or disorder, age, gender, socioeconomic characteristics, smoking habit, psychological or emotional distress, personality trait, cognitive appraisals and coping strategies.

#### **2.3.1 History of previous low back pain/disorder**

A previous pain/injury history to the lower back is consistently a strong risk factor for future reports of LBP in the work environment (Dempsey et al., 1997; National Institute of Occupational Safety and Health, 1997). In women during/after pregnancy, there is strong evidence for the risk of developing LBP in those who had previous LBP and previous lumbopelvic pain during or after pregnancy (Wu et al., 2004).

#### **2.3.2 Age**

82 Low Back Pain Pathogenesis and Treatment

manufacturing company. An association was found between the psychosocial risk factors of low job control and high job demand and the development of LBP only in workers with

The main focus in the relationship between psychosocial factors and LBP has chiefly been work related in most studies. However, there is increasing awareness that psychosocial factors which are unrelated to work, may also play an important role in the development of LBP. These psychosocial factors are characterized by family or social or emotional support, leisure time activity or social contact and participation, spousal relationship and housework satisfaction. Only a few prospective studies have addressed individual and outside of work

Yip et al. (2004), studying 417 middle-aged women in a case control study, found an association between psychosocial stress related to housework and LBP after adjusted for working status and source of recruitment. However, no association was found between self reported poor relationship with cohabitants, housework satisfaction, living alone and the risk of LBP. Likewise, a cross sectional longitudinal study by Barnekow-Bergkvist (1998) described earlier found no association between physical activity at leisure time and low back

Simiarly, Hoogendoorn et al.'s review (2000), as described above, also included assessment of psychosocial factors in private life such as family support, presence of a close friend or neighbour, social contact, social participation, emotional support and concluded that insufficient evidence was found for an effect of psychosocial factors in private life because

However, Brulin et al. (1998) conducted a cross sectional study of 361 women in a Swedish home care service and found having children at home decreased the risk of low back complaints (OR 0.5), even after age adjusted. It was argued that having children in the family can protect against social isolation, and that social isolation was found to increase the risk of low back pain (Frymoyer & Cats-Baril, 1987). The strength of this study lies in its combined focus on sociodemographic, physical and psychosocial factors at work and physical activity during leisure time. This study is based on a single occupation therefore the sample may not be representative of the general population. Likewise, Thorbjornsson et al. (1998), in a longitudinal study over 24 years, found that social relationship satisfaction

Since the complexity of LBP may be represented by the interactive effect of psychosocial, biomechanical and individual factors (Chany et al., 2006), a better understanding in individual factors may elucidate the complex reactions. These individual factors are characterized by history of previous low back pain or disorder, age, gender, socioeconomic characteristics, smoking habit, psychological or emotional distress, personality trait,

has a long-term effect on LBP among 252 women and 232men.

high physical exposures.

**2.2 Psychosocial role (outside of work)**

environmental psychosocial factors.

symptoms.

the data were very limited.

**2.3 Individual characteristics**

cognitive appraisals and coping strategies.

Age has been suggested to play a role in the development of LBP in a review by Dempsey et al. (1997). The review found that the occurrence of LBP increases with increasing age up to about 50 to 60 years of age in several community-based studies, after which there seems to be a decline. Several biological plausibility of the role of age in LBP exist, in that accumulated work-related spinal damage including microtruama, natural degeneration of the spine, and decreased spinal load bearing capacity. With regards to LBP during pregnancy, Wu et al.'s review (2004) found the evidence for maternal age was conflicting. In the review, nine studies suggested a higher risk in younger women, two studies suggested a higher risk for older women, and 12 had no effect.

#### **2.3.3 Gender**

The risk of LBP is higher among women as consistently shown in community-based surveys, with odds ratios varying between 1.30 to 1.57 (Houtman et al., 1994; Skovron et al., 1994). The risk of back pain increases by twofold for women with back pain history and increases for women who have been pregnant before (Ostgaard & Andersson, 1991). Women are expected to suffer from more lower back pain because of their wider pelvis, the stress of hormonal changes, and childbirth (Meisler, 2003). Retrospective studies showed that 10-25% of women with chronic LBP report the first symptom of back pain during pregnancy (Biering-Sorensen, 1983; Svensson et al., 1990). During pregnancy, 50%-80% of women experience some degree of pregnancy-related low back pain (PLBP) and pelvic girdle pain (PPGP). Women who have previously had pelvic pain during pregnancy experience a relapse during 85% of a subsequent pregnancy (Mens et al., 1996). The pain symptoms often impact on daily activities, sleep and sometimes lead to work absenteeism and even chronic disability. A study shows lower quality of life during pregnancy among women with back problems (Olsson & Nilsson-Wikmar, 2004). Among these women who are affected by LBP, pain sometimes becomes chronic or recurrent (Larsen et al., 1999; Ostgaard et al., 1997).

#### **2.3.4 Socioeconomic characteristics**

It was found that low back symptoms were consistently more common among the women in the highest socioeconomic class (professionals, managers, and salaried employees) (Barnekow-Bergkvist et al., 1998). Likewise, Papageorogiou et al. (1997) found significant associations between LBP and higher social class and perceived inadequacy of income in a prospective population-based cohort study of 1412 working adults, the association was more marked in women. It was argued that higher stress levels among women in high and middle socioeconomic classes because of the combination of work-related stress and stress related to responsibilities for the family (Lundberg, 1999).

Psychosocial Risk Factors in the Development of LBP 85

during the preceding 5 years. When women and men were analyzed separately, no systemic

Mehling et al. (2005), in a cross sectional study of 1180 transit operators, found alexithymia (deficit in emotional awareness) was associated with higher odds of LBP after controlled for demographic, behavioral and physical and psychosocial factors (OR=2.0, 95% CI 1.31-3.0). The association was stronger in women (OR=4.35) than in men (OR=1.83) with the factor 'difficult to identifying feelings' showing the strongest association. However, the authors pointed out that the study is limited by not controlling for depression or somatization, both

While the presence of psychosocial factors may be characteristic of the job and work environment, the biomechanical response of the individual to these psychosocial stressors may be dependent on the individual's perceptions about stress (Chany et al., 2006).

A study found that personality traits have association with muscle recruitment patterns, which may lead to variations in spinal loading as the individual is under psychosocial stress (Marras et al., 2000). The hypothesis posits that job-matched personality traits allow the individual to generate the appropriate biomechanical response with reduction of spinal loading (Chany et al., 2006). Contrarily, job-mismatched personality traits may provoke psychosocial stress which increases the trunk muscle activities, in turn, causes an increase in

Chany et al. (2006), in a laboratory-based study of 12 experienced and 12 novice materials handlers (3 females and 21 males), ages ranged from 19 to 33 years, investigated the long term effect of repetitive lifting on the spinal loading of workers with different personality types. They found that intuitors personality had higher shear spinal loading compared with sensor type, and that perceiver personality had higher compressive and shear forces

They suggested explanations for the trends, in that a personality of intuitors prefers to learn new skills, repetitive lifting task seems less matched to the intuitors' preferences, which was the primary influence on how the intuitors coactivated their muscles to high levels resulting in high spinal loads. Perceivers enjoy variations in circumstances, whereas judgers prefer scheduled work plans, the task appears to be a better match for the judgers (Chany et al., 2006). They concluded that inherent personality characteristics may play a role in one's motor control strategies when performing a repetitive lifting task and that the perceived stress (of repetitive lifting) manifests itself by increases in muscle coactivity which results in higher spinal loading. The study was designed to assess the spinal loading during lifting, with the assumption that increased spinal loading is associated with LBP, therefore, these

Cognitive variables are among the best predictors of LBP-related chronic disability (Truchon & Fillion, 2000), but not extensively documented at the early stage of LBP (Truchon, 2001).

Personality is one of the factors that may provide more clues to individual responses.

differences were observed regarding the estimated ORs of LBP.

factors are associated with alexithymia and LBP.

**2.3.7 Personality trait**

the spinal loading.

compared with judgers personality trait.

results cannot be used to determine in other work situations.

**2.3.8 Cognitive appraisals and coping strategies**

#### **2.3.5 Smoking**

Smoking is suggested to be a risk factor for low back disorders. NIOSH's review (National Institute of Occupational Safety and Health, 1997) found that the evidence is conflicting as smoking history has a positive relationship with low back pain, sciatica or intervertebral herniated disc in some studies whereas in others the relationship was negative. Josephson et al. (1998) described earlier found no association between smoking and LBP among female nursing personnel. Whereas McaGregor et al. (2004), investigation of 1064 women in a case control study, found smoking was associated with LBP.

Several explanations for the association have been proposed (Dempsey et al., 1997; National Institute of Occupational Safety and Health, 1997). It is speculated that back pain is caused by coughing associated with smoking which increases intradiscal pressure, leading to disc bulging and herniation. Another explanation postulated is nicotine's effect in diminishing blood flow to vertebral body and thus impacting discal metabolism and reducing mineral content of bone causing microfractures. However, it has been pointed out that a number of confounding risk factors have been linked with smoking, including lower economic class, education level, occupational exposure to heavy work, and psychosocial and life style factors (Dempsey et al., 1997).

#### **2.3.6 Psychological/emotional distress**

Given that psychological or emotional distress such as anxiety and depression may arise from work environment, they may also result from non-work environment. Strong evidence suggests that high comorbidity between psychological distress and pain, in particular among chronic pain patients (Gatchel & Gardea, 1999). The comorbid presentation of pain and depression is observed in as many as 50% of patients who suffer from chronic pain conditions (Gallagher, 2003). Similarly, in a recent review by Ramond et al, (2011), as described earlier, the association between negative LBP outcome and depression and psychological distress were found.

A sex-specific effect of anxiety on pain report is apparent. There is a significant association between anxiety and pain report in men but not in women. However, among women, depression, catastrophizing, anxiety sensitivity, stress, low energy and pain reports were significantly associated (Korovessis, 2010; Robinson et al., 2005).

Variability in psychological distress has been linked to LBP in women. Quint et al. (1998) in a case control study found that women had higher levels of psychological distress than men in a group of hospitalized patients with LBP. Clays et al. (2007), in the study of Belstress workers described above, found feeling depressed increased the relative risk for LBP in 30% women. However, Robinson et al. (2005), in a cross sectional study of 53 chronic LBP patients, found significant relationships between anxiety and the induced pain for men but not for women.

Some authors have reported other psychological variables to be related to LBP such as stressful life events and deficit in emotional awareness. Yip et al. (2004), as described above, found an association between stressful life event in the past 12 months and LBP with adjustments. However, Skillgate et al. (2007) failed to support this relationship and found no association between LBP and two or more life events or critical life changes experienced during the preceding 5 years. When women and men were analyzed separately, no systemic differences were observed regarding the estimated ORs of LBP.

Mehling et al. (2005), in a cross sectional study of 1180 transit operators, found alexithymia (deficit in emotional awareness) was associated with higher odds of LBP after controlled for demographic, behavioral and physical and psychosocial factors (OR=2.0, 95% CI 1.31-3.0). The association was stronger in women (OR=4.35) than in men (OR=1.83) with the factor 'difficult to identifying feelings' showing the strongest association. However, the authors pointed out that the study is limited by not controlling for depression or somatization, both factors are associated with alexithymia and LBP.

#### **2.3.7 Personality trait**

84 Low Back Pain Pathogenesis and Treatment

Smoking is suggested to be a risk factor for low back disorders. NIOSH's review (National Institute of Occupational Safety and Health, 1997) found that the evidence is conflicting as smoking history has a positive relationship with low back pain, sciatica or intervertebral herniated disc in some studies whereas in others the relationship was negative. Josephson et al. (1998) described earlier found no association between smoking and LBP among female nursing personnel. Whereas McaGregor et al. (2004), investigation of 1064 women in a case

Several explanations for the association have been proposed (Dempsey et al., 1997; National Institute of Occupational Safety and Health, 1997). It is speculated that back pain is caused by coughing associated with smoking which increases intradiscal pressure, leading to disc bulging and herniation. Another explanation postulated is nicotine's effect in diminishing blood flow to vertebral body and thus impacting discal metabolism and reducing mineral content of bone causing microfractures. However, it has been pointed out that a number of confounding risk factors have been linked with smoking, including lower economic class, education level, occupational exposure to heavy work, and psychosocial and life style

Given that psychological or emotional distress such as anxiety and depression may arise from work environment, they may also result from non-work environment. Strong evidence suggests that high comorbidity between psychological distress and pain, in particular among chronic pain patients (Gatchel & Gardea, 1999). The comorbid presentation of pain and depression is observed in as many as 50% of patients who suffer from chronic pain conditions (Gallagher, 2003). Similarly, in a recent review by Ramond et al, (2011), as described earlier, the association between negative LBP outcome and depression and

A sex-specific effect of anxiety on pain report is apparent. There is a significant association between anxiety and pain report in men but not in women. However, among women, depression, catastrophizing, anxiety sensitivity, stress, low energy and pain reports were

Variability in psychological distress has been linked to LBP in women. Quint et al. (1998) in a case control study found that women had higher levels of psychological distress than men in a group of hospitalized patients with LBP. Clays et al. (2007), in the study of Belstress workers described above, found feeling depressed increased the relative risk for LBP in 30% women. However, Robinson et al. (2005), in a cross sectional study of 53 chronic LBP patients, found significant relationships between anxiety and the induced pain for men but

Some authors have reported other psychological variables to be related to LBP such as stressful life events and deficit in emotional awareness. Yip et al. (2004), as described above, found an association between stressful life event in the past 12 months and LBP with adjustments. However, Skillgate et al. (2007) failed to support this relationship and found no association between LBP and two or more life events or critical life changes experienced

significantly associated (Korovessis, 2010; Robinson et al., 2005).

control study, found smoking was associated with LBP.

**2.3.5 Smoking**

factors (Dempsey et al., 1997).

**2.3.6 Psychological/emotional distress**

psychological distress were found.

not for women.

While the presence of psychosocial factors may be characteristic of the job and work environment, the biomechanical response of the individual to these psychosocial stressors may be dependent on the individual's perceptions about stress (Chany et al., 2006). Personality is one of the factors that may provide more clues to individual responses.

A study found that personality traits have association with muscle recruitment patterns, which may lead to variations in spinal loading as the individual is under psychosocial stress (Marras et al., 2000). The hypothesis posits that job-matched personality traits allow the individual to generate the appropriate biomechanical response with reduction of spinal loading (Chany et al., 2006). Contrarily, job-mismatched personality traits may provoke psychosocial stress which increases the trunk muscle activities, in turn, causes an increase in the spinal loading.

Chany et al. (2006), in a laboratory-based study of 12 experienced and 12 novice materials handlers (3 females and 21 males), ages ranged from 19 to 33 years, investigated the long term effect of repetitive lifting on the spinal loading of workers with different personality types. They found that intuitors personality had higher shear spinal loading compared with sensor type, and that perceiver personality had higher compressive and shear forces compared with judgers personality trait.

They suggested explanations for the trends, in that a personality of intuitors prefers to learn new skills, repetitive lifting task seems less matched to the intuitors' preferences, which was the primary influence on how the intuitors coactivated their muscles to high levels resulting in high spinal loads. Perceivers enjoy variations in circumstances, whereas judgers prefer scheduled work plans, the task appears to be a better match for the judgers (Chany et al., 2006). They concluded that inherent personality characteristics may play a role in one's motor control strategies when performing a repetitive lifting task and that the perceived stress (of repetitive lifting) manifests itself by increases in muscle coactivity which results in higher spinal loading. The study was designed to assess the spinal loading during lifting, with the assumption that increased spinal loading is associated with LBP, therefore, these results cannot be used to determine in other work situations.

#### **2.3.8 Cognitive appraisals and coping strategies**

Cognitive variables are among the best predictors of LBP-related chronic disability (Truchon & Fillion, 2000), but not extensively documented at the early stage of LBP (Truchon, 2001).

Psychosocial Risk Factors in the Development of LBP 87

psychosocial factors are definitively related to LBP because of the inconsistency of the results. It seems that individual's reactions to psychosocial work characteristics, for example job dissatisfaction and job stress, are more consistently related to LBP than are the psychosocial work characteristics themselves, for example work demand, low job control, low social support (Davis & Heaney, 2000). However, low job control and high work demand are associated with LBP in people with increased physical exposures (Vandergrift

The inconsistent results in the studies may be attributed by some methodological problems in the majority of studies. Earlier studies involved working population of specific occupation and were not population based therefore limits the generalizability of the results. In an extensive review by Davis et al. (2000), two major methodological limitations were revealed in the critique of 66 articles pertaining to psychosocial work factors and LBP. First, very few studies had adequately controlled the potential confounding effect of biomechanical factors. Second, there is a paucity of high quality measures of both psychosocial work characteristics and biomechanical demands. Another major limitation includes insufficient prospective study designs rendering weak causal inferences. Thus, it is argued that psychological distress may simply be a consequence of chronic LBP without etiologic role in the development of low back disorder, or it may play a role in the etiology of LBP. Furthermore, there is random error in the operationalization of LBP and

It is therefore important to consider the multitude of psychosocial factors and physiologic factors that are intertwined and ultimately produce the back pain experience. Understanding the complex and the interactive processes involved in LBP will not only help to predict those who develop LBP and chronic disability, as well as to develop more effective treatments for LBP patients, but also to design better epidemiological and

Barnekow-Bergkvist, M., G. Hedberg, U. Janlert, & E. Jansson. (1998). Determinants of self-

Biering-Sorensen, F. (1983). A prospective study of low back pain in a general population. I.

Bongers, P. M., C. R. de Winter, M. A. Kompier, & V. H. Hildebrandt. (1993). Psychosocial

Brulin, C., B. Gerdle, B. Granlund, J. Hoog, A. Knutson, & G. Sundelin. (1998). Physical and

Busch, H. (2005). Appraisal and coping processes among chronic low back pain patients.

reported neck-shoulder and low back symptoms in a general population. *Spine,* 23,

Occurrence, recurrence and aetiology. *Scandivian Journal of Rehabilitation Medicine,*

factors at work and musculoskeletal disease. *Scandivian Journal of Work*

psychosoical work-related risk factors associated with musculoskeletal symptoms among home care personnel. *Scandinavian Journal of Caring Science,* 12, pp. 104-110. Burton, A. K. & E. Erg. (1997). Back injury and work loss. Biomechanical and psychosocial

psychosocial variables due to the use of non-standardized questionnaires.

intervention studies by the inclusion of potential psychosocial covariates.

*Environmental Health,* 19, 5, pp. 297-312.

influences. *Spine,* 22, 21, pp. 2575-2580.

*Scandinavian Journal of Caring Science,* 19, 4, pp. 396-402.

et al., 2012).

**4. References**

2, pp. 235-243.

15, pp. 71-79.

Truchon's review found that there may be a link that exists between a negative cognitive appraisal, negative affective state (depression, anxiety or anger) that it generates, and passive coping strategies (avoid the threat). Negative cognitive appraisals include pain catastrophizing, blaming oneself or others, anticipation of negative consequences associated with the disease, inaccurate interpretations of the significance of the physical symptoms and the effectiveness of the medical treatments.

Studies have focused on how pain catastrophizing has influenced LBP (Grant et al., 2002; Robinson et al., 2005). Pain catastrophizing is defined as an 'overappraisal' of the negative aspects/consequences of an experience (Raak et al., 2002) wherein an individual has a tendency to focus on and exaggerate the threat value of painful stimuli and negatively evaluate one's ability to deal with pain. Grant et al. (2002) studied the associations among pain appraisals, coping strategies, personal characteristics, perceived spousal responses and daily changes in mood and pain in 88 chronic LBP women. They found that catastrophizing appraisals and praying and hoping coping strategies were associated with an increase in negative mood or pain. For chronic back pain patients, catastrophizing was associated with increased pain intensity, anxiety and depression levels, after controlling for pain (Grant et al., 2002).

Likewise, Robinson et al. (2005), in a cross sectional study of 53 chronic LBP patients, found significant relationships between pain catastrophizing measures and the induced pain for men but not for women. In a similar vein, there seems to be a link between pain catastrophizing and pain reporting. Crombez et al. (2002) found pain catastrophizing (as measured by the Pain Catastrophizing Scale) was related to overpredictions of pain in 37 patients with LBP during performance tests of toe touch in standing position and straight leg raise in supine position.

Other coping strategy that exists may also have an effect on LBP. Busch (2005) interviewed 22 chronic LBP patients (15 women and 7 men) of working age in a rehabilitation clinic in Sweden and found that the majority of participants used disregarding strategy in response to chronic LBP. This disregarding strategy process developed from a psychological defense to a conscious coping strategy with changing pain-related behaviors. The change in painrelated behaviours of an increased sense of responsibility for pain and pain management helped rehabilitation of chronic LBP.

#### **3. Conclusion**

In an attempt to uncover a representative sample of publications that have investigated the psychosocial risk factors for developing LBP, there are some conclusions that may be drawn, although this is not a fully exhaustive review of publications. Most of the research has focused on LBP and psychosocial risk factors associated with work environment and much less in the area of factors associated with outside of work environment and individual characteristics. Women seem to have different psychosocial risk factors from men for the development of LBP.

The current state of knowledge suggests that psychosocial factors at work play an important role in the development of LBP, although the underlying mechanisms are not fully understood (Bongers et al., 1993; Hoogendoorn et al., 2000; National Institute of Occupational Safety and Health, 1997; Pincus et al., 2002b). It is unclear as to which

Truchon's review found that there may be a link that exists between a negative cognitive appraisal, negative affective state (depression, anxiety or anger) that it generates, and passive coping strategies (avoid the threat). Negative cognitive appraisals include pain catastrophizing, blaming oneself or others, anticipation of negative consequences associated with the disease, inaccurate interpretations of the significance of the physical symptoms and

Studies have focused on how pain catastrophizing has influenced LBP (Grant et al., 2002; Robinson et al., 2005). Pain catastrophizing is defined as an 'overappraisal' of the negative aspects/consequences of an experience (Raak et al., 2002) wherein an individual has a tendency to focus on and exaggerate the threat value of painful stimuli and negatively evaluate one's ability to deal with pain. Grant et al. (2002) studied the associations among pain appraisals, coping strategies, personal characteristics, perceived spousal responses and daily changes in mood and pain in 88 chronic LBP women. They found that catastrophizing appraisals and praying and hoping coping strategies were associated with an increase in negative mood or pain. For chronic back pain patients, catastrophizing was associated with increased pain intensity, anxiety and depression levels, after controlling for pain (Grant et

Likewise, Robinson et al. (2005), in a cross sectional study of 53 chronic LBP patients, found significant relationships between pain catastrophizing measures and the induced pain for men but not for women. In a similar vein, there seems to be a link between pain catastrophizing and pain reporting. Crombez et al. (2002) found pain catastrophizing (as measured by the Pain Catastrophizing Scale) was related to overpredictions of pain in 37 patients with LBP during performance tests of toe touch in standing position and straight

Other coping strategy that exists may also have an effect on LBP. Busch (2005) interviewed 22 chronic LBP patients (15 women and 7 men) of working age in a rehabilitation clinic in Sweden and found that the majority of participants used disregarding strategy in response to chronic LBP. This disregarding strategy process developed from a psychological defense to a conscious coping strategy with changing pain-related behaviors. The change in painrelated behaviours of an increased sense of responsibility for pain and pain management

In an attempt to uncover a representative sample of publications that have investigated the psychosocial risk factors for developing LBP, there are some conclusions that may be drawn, although this is not a fully exhaustive review of publications. Most of the research has focused on LBP and psychosocial risk factors associated with work environment and much less in the area of factors associated with outside of work environment and individual characteristics. Women seem to have different psychosocial risk factors from men for the

The current state of knowledge suggests that psychosocial factors at work play an important role in the development of LBP, although the underlying mechanisms are not fully understood (Bongers et al., 1993; Hoogendoorn et al., 2000; National Institute of Occupational Safety and Health, 1997; Pincus et al., 2002b). It is unclear as to which

the effectiveness of the medical treatments.

al., 2002).

leg raise in supine position.

**3. Conclusion**

development of LBP.

helped rehabilitation of chronic LBP.

psychosocial factors are definitively related to LBP because of the inconsistency of the results. It seems that individual's reactions to psychosocial work characteristics, for example job dissatisfaction and job stress, are more consistently related to LBP than are the psychosocial work characteristics themselves, for example work demand, low job control, low social support (Davis & Heaney, 2000). However, low job control and high work demand are associated with LBP in people with increased physical exposures (Vandergrift et al., 2012).

The inconsistent results in the studies may be attributed by some methodological problems in the majority of studies. Earlier studies involved working population of specific occupation and were not population based therefore limits the generalizability of the results. In an extensive review by Davis et al. (2000), two major methodological limitations were revealed in the critique of 66 articles pertaining to psychosocial work factors and LBP. First, very few studies had adequately controlled the potential confounding effect of biomechanical factors. Second, there is a paucity of high quality measures of both psychosocial work characteristics and biomechanical demands. Another major limitation includes insufficient prospective study designs rendering weak causal inferences. Thus, it is argued that psychological distress may simply be a consequence of chronic LBP without etiologic role in the development of low back disorder, or it may play a role in the etiology of LBP. Furthermore, there is random error in the operationalization of LBP and psychosocial variables due to the use of non-standardized questionnaires.

It is therefore important to consider the multitude of psychosocial factors and physiologic factors that are intertwined and ultimately produce the back pain experience. Understanding the complex and the interactive processes involved in LBP will not only help to predict those who develop LBP and chronic disability, as well as to develop more effective treatments for LBP patients, but also to design better epidemiological and intervention studies by the inclusion of potential psychosocial covariates.

#### **4. References**

Psychosocial Risk Factors in the Development of LBP 89

Josephson, M. (1998). Workplace factors and care seeking for low back pain among female

Korovessis, P., Repantis, T. & Baikousis, A. (2010). Factors affecting low back pain in adolescents. *Journal of Spinal Disorders and Techniques, 23*(8), 513-20. Larsen, E. C., C. Wilken-Jensen, A. Hansen, D. V. Jensen, S. Johansen, H. Minck, M.

Lundberg, U. (1999). Stress responses in low-status jobs and their relationship to health

Luo, X., R. Pietrobon, S. X. Sun, G. G. Liu, & L. Hey. (2004). Estimates and patterns of direct

MacGregor, A. J., T. Andrew, P. N. Sambrook, & T. D. Spector. (2004). Structural,

Marras, W. S., K. G. Davis, C. A. Heaney, A. B. Maronitis, & W. G. Allread. (2000). The

Mehling, W. E. & N. Krause. (2005). Are difficulties perceiving and expressing emotions

public transit operators. *Journal of Psychosomatic Research,* 58, 1, pp. 73-81. Meisler, j. g. (2003). Toward optimal health: The experts discuss management of low back

Melzack, R. & P. Wall. (1965). Pain mechanisms: a new theory. *Science,* 150, 699, pp. 971-979. Mens, J. M., A. Vleeming, R. Stoeckart, H. J. Stam, & C. J. Snijders. (1996). Understanding

National Institute of Occupational Safety and Health. (1997). Workplace use of back belts:

Olsson, C. & L. Nilsson-Wikmar. (2004). Health-related quality of life and physical ability

Ostgaard, H. C. & G. B. Andersson. (1991). Previous back pain and risk of developing back

Ostgaard, H. C., G. Zetherstrom, & E. Roos-Hansson. (1997). Back pain in relation to

Papageorgiou, A. C., G. J. Macfarlane, E. Thomas, P. R. Croft, M. I. Jayson, and A. J. Silman.

Pincus, T., A. K. Burton, S. Vogel, & A. P. Field. (2002a). A systematic review of psychosocial

Public Health Service, Centers for Disease Control and Prevention.

*Obstetricia et Gynecologica Scandinavica,* 83, 4, pp. 351-357.

pregnancy: a 6-year follow-up. *Spine,* 22, 24, pp. 2945-2950.

pain in a future pregnancy. *Spine,* 16, 4, pp. 432-436.

pain in women. *Journal of Women's Health,* 12, 10, pp. 953-959.

female twins. *Arthritis and Rheumatism,* 51, 2, pp. 160-167.

*Gynecologica Scandinavica,* 78, 2, pp. 105-110.

the lumbar spine. *Spine*, 23, 3045-3054.

472.

162-172.

1369.

1137-1142.

pain. *Spine,* 27, pp. E209-E120.

*Spine,* 29, 1, pp. 79-86.

nursing personnel. *Scandivian Journal of Work Environmental Health,* 24, 6, pp. 465-

Wormslev, M. Davidsen, & T. M. Hansen. (1999). Symptom-giving pelvic girdle relaxation in pregnancy. I: Prevalence and risk factors. *Acta Obstetricia et*

risks: Musculoskeletal disorders. *Annals New York Academy of Sciences,* 896, 1, pp.

health care expenditures among individuals with back pain in the United States.

psychological, and genetic influences on low back and neck pain: A study of adult

influence of psychsocial stress, gender, and personality on mechanical loading of

associated with low-back pain? The relationship between lack of emotional awareness (alexithymia) and 12-month prevalence of low-back pain in 1180 urban

peripartum pelvic pain. Implications of a patient survey. *Spine,* 21, 11, pp. 1363-

Review and recommendations. U.S.Department of Health and Human Services,

among pregnant women with and without back pain in late pregnancy. *Acta*

(1997). Psychosocial factors in the workplace--do they predict new episodes of low back pain? Evidence from the South Manchester Back Pain Study. *Spine,* 22, 10, pp.

factors as predictors of chronicity/ disability in prospective cohorts of low back

Chany, A. M., J. Parakkat, G. Yang, D. L. Burr, & W. S. Marras. (2006). Changes in spine

Clays, E., Bacquer D. De, F. Leynen, M. Kornitzer, F. Kittel, & Backer G. De. (2007). The

Cohen, S. P., Gallagher, R. M., Davis, S. A., Griffith, S. R. & Carragee, E. J. (2011). Spine-area

Crombez, G., C. Eccleston, J. W. Vlaeyen, D. Vansteenwegen, R. Lysens, & P. Eelen. (2002).

Davis, K. G. & C. A. Heaney. (2000). The relationship between psychosocial work

Dempsey, P. G., A. Burdorf, & B. S. Webster. (1997). The influence of personal variables on

Dionne, C. E., Korff M. Von, T. D. Koepsell, R. A. Deyo, W. E. Barlow, & H. Checkoway.

Frymoyer, J. W. & W. Cats-Baril. (1987). Predictors of low back pain disability. *Clinical*

Gallagher, R. M. 2003. The pain depression conundrum: bridging the body and mind. 16

Gatchel, R. J. & M. A. Gardea. (1999). Psychosocial issues: their importance in predicting

Grant, L., B. Long, & J. D. Willms. (2002). Women's adaptation to chronic back pain: Daily

Hartvigsen, J., S. Lings, C. Leboeuf-Yde, & L. Bakketeig. (2004). Psychosocial factors at work

Hemingway, H. & M. Marmot. (1999). Evidence based cardiology: psychosocial factors in

prospective cohort studies. *Bristish Medical Journal,* 318, 7196, pp. 1460-1467. Hooftman, W., M. van Poppel, & A. van der Beek. (2004). Gender differences in the relations

complaints. *Scandivian Journal of Work Environmental Health,* 30, pp. 261-278. Hoogendoorn, W. E., M. N. van Poppel, P. M. Bongers, B. W. Koes, & L. M. Bouter. (2000).

Houtman, I. L., P. M. Bongers, & P. G. Smulders. (1994). Psychosocial stressors at work and

frequency, and personality. *The Spine Journal,* 6, 3, pp. 296-305.

Belstress study. *Spine,* 32, 2, pp. 262-268.

treatment. *The Spine Journal,* (In press).

*Biomechanics,* 15, 6, pp. 389-406.

*Community Health,* 55, 7, pp. 455-468.

back pain. *Spine,* 25, 16, pp. 2114-2125.

17, 1, pp. 149-166.

*Medicine,* 61, 1, pp. 2.

139-145.

*Orthopaedics and Related Research,* 221, pp. 89-98.

responses. *Journal of Health Psychology,* 7, 5, pp. 545-563.

generalization. *Health Psychology,* 21, 6, pp. 573-578.

*Occupational and Environmental Medicine,* 39, 8, pp. 748-759.

loading patterns throughout the workday as a function of experience, lift

impact of psychosocial factors on low back pain: longitudinal results from the

pain in military personnel: a review of epidemiology, etiology, diagnosis, and

Exposure to physical movements in low back pain patients: restricted effects of

characteristics and low back pain: underlying methodological issues. *Clinical*

work-related low-back disorders and implications for future research. *Journal of*

(2001). Formal education and back pain: a review. *Journal of Epidemiology and*

September 2011. Available from: http://www.medscape.com/viewprogram/2030.

disability, response to treatment, and search for compensation. *Neurologic Clinics,*

appraisals and coping strategies, personal characteristics and percieved spousal

in relation to low back pain and consequences of low back pain; a systematic, critical review of prospective cohort studies. *Occupational and Environmental*

the aetiology and prognosis of coronary heart disease. Systematic review of

between work-related physical and psychosocial risk factors and musculoskeletal

Systematic review of psychosocial factors at work and private life as risk factors for

musculoskeletal problems. *Scandivian Journal of Work Environmental Health,* 20, pp.

**6**

*Israel*

**Evaluation and Management of Lower**

Back pain is one of the most common complaints that brings patients to be examined by a physician (Moore, 2010). Pain may originate from a variety of tissues, including intervertebral disks, vertebrae, ligaments, neural structures, muscles, and fascia, or present as referred pain from adjacent pathology, such as peptic ulcers, pancreatitis, pyelonephritis, aortic aneurysm, and more (Henschke, et al., 2009). Nonspecific low back pain is typically managed with symptomatic care and physical therapy, with up to 90% of patients improving substantially over 3 months. It is such a common condition that the American College of Physicians has issued guidelines with a mandate against imaging patients for the

Serious, life-threatening diseases are uncommon causes of back pain; malignancy, ankylosing spondylitis, and infection together account for less than 5% of back pain cases in a typical primary care practice (Dagenais, et al., 2010). However, missing such a critical diagnosis represents a serious concern for every practitioner; thus complaints of back pain

The spine is one of the most common sites of metastasis with close to 20,000 cases of spine metastases arising each year in the United States (Sciubba, et al., 2009). The most common primary tumors in patients with metastases are breast, lung, prostate, and kidney cancer (Guillevin, et al., 2007). In close to 15% of oncology patients, the primary presenting symptoms of malignancy are related to spinal metastases. In these patients, the most common underlying pathology is lung cancer, followed by breast cancer in females and

When the patient's history is taken properly, a thorough physical examination is conducted, and appropriate diagnostic tests are performed, the physician can determine with a high level of accuracy whether an individual patient is suffering from nonspecific ("simple") back pain, or whether an underlying, potentially catastrophic disease is triggering the pain (Bach,

often lead to multiple imaging studies and consultations (Venkitaraman, et al., 2010).

prostate cancer in male patients (Chamberlain & Kormanik, 1999).

**1. Introduction**

et al., 1990).

first month after pain onset (Chou, 2010).

**Back Pain in Oncological Patients**

Joshua E. Schroeder1, Yair Barzilay1, Amir Hasharoni1,

Leon Kaplan1, José E. Cohen2 and Eyal Itshayek2

*Hadassah—Hebrew University Medical Center Jerusalem,*

*Hadassah—Hebrew University Medical Center Jerusalem,*

*1Departments of Orthopedic Surgery,*

*2Departments of Neurosurgery,*

## **Evaluation and Management of Lower Back Pain in Oncological Patients**

Joshua E. Schroeder1, Yair Barzilay1, Amir Hasharoni1, Leon Kaplan1, José E. Cohen2 and Eyal Itshayek2 *1Departments of Orthopedic Surgery, Hadassah—Hebrew University Medical Center Jerusalem, 2Departments of Neurosurgery, Hadassah—Hebrew University Medical Center Jerusalem, Israel*

#### **1. Introduction**

90 Low Back Pain Pathogenesis and Treatment

Pincus, T., J. W. Vlaeyen, N. A. Kendall, M. R. Von Korff, D. A. Kalauokalani, & S. Reis.

Punnett, L., A. Pruss-Utun, D. I. Nelson, M. A. Fingerhut, J. Leigh, S. Tak, & S. Phillips.

Raak, R., K. Wikblas, A. Raak, M. Carlsson, & L. Wahren. (2002). Catastrophizing and health

Ramond, A., Bouton, C., Richard, I., Roquelaure, Y., Baufreton, C., Legrand, E. & Huez, J.-F.

Robinson, M. E., E. A. Dannecker, S. Z. George, J. Otis, J. W. Atchison, & R. B. Fillingim.

Skillgate, E., E. Vingard, M. Josephson, T. Theorell, & L. Alfredsson. (2007). Life events and

Skovron, M. L., M. Szpalski, M. Nordin, C. Melot, & D. Cukier. (1994). Sociocultural factors and back pain: a population-based study in Belgian adults. *Spine,* 19, pp. 129-137. Svensson, H. O., G. B. Andersson, A. Hagstad, & P. O. Jansson. (1990). The relationship of low-back pain to pregnancy and gynecologic factors. *Spine,* 15, pp. 371-375. Thorbjornsson, C. O., L. Alfredsson, K. Fredriksson, M. Koster, H. Michelsen, E. Vingard, M.

occupations. *Occupational and Environmental Medicine,* 55, 2, pp. 84-90. Truchon, M. (2001). Determinants of chronic disability related to low back pain: Towards an integrative biopsychosoical model. *Disability and Rehabilitation,* 23, 17, pp. 758-767. Truchon, M. & L. Fillion. (2000b). Biopsychosocial determinants of chronic disability and low-back pain: a review. *Journal of Occupational Rehabilitation,* 10, pp. 117-142. Vandergrift, J. L., Gold, J. E., Hanlon, A. & Punnett, L. (2012). Physical and psychological

directions for the future. *Spine,* 27, 5, pp. E133-E138.

back pain. *Rehabilitation Nursing Journal,* 27, 3, pp. 110-117.

*Ihre Grenzgebiete,* 136, 5, pp. 444-450.

*Community Health,* 61, 4, pp. 356-361.

systematic review. *Family Practice, 28*, 12-21.

*of Pain and Symptom Management,* 6, 7, pp. 463-470.

*Occupational Environmental Medicine, 69*, 29-34.

*International,* 25, 4, pp. 358-369.

493-500.

(2002b). Cognitive-behavioral therapy and psychosocial factors in low back pain:

(2005). Estimating the global burden of low back pain attributable to combined occupational exposures. *American Journal of Industrial Medicine,* 48, 6, pp. 459-469. Quint, U., H. Hasenburg, T. Patsalis, & G. H. Franke. (1998). Psychological stress of

inpatients with acute and chronic lumbar syndrome. *Zeitschrift fur Orthopadie und*

related quality of life - a 6- year follow-up of subjects suffering from chronic low

(2011). Psychosocial risk factors for chronic low back pain in primary care- a

(2005). Sex differences in the associations among psychological factors and pain report: a novel psychophysical study of patients with chronic low back pain. *Journal*

the risk of low back and neck/shoulder pain of the kind people are seeking care for: results from the MUSIC-Norrtalje case-control study. *Journal of Epidemiology and*

Torgen, & A. Kilbom. (1998). Psychosocial and physical risk factors associated with low back pain: a 24 year follow up among women and men in a broad range of

ergonomic risk factors for low back pain in automobile manufacturing workers.

To what extent do current and past physical and psychosocial occupational factors explain care-seeking for low back pain in a working population? *Spine,* 25, 4, pp.

Ostgaard. (2004). Pregnancy-related pelvic girdle pain (PPP), I: Terminology, clinical presentation, and prevalence. *European Spine Journal,* 13, pp. 575-589. Yip, Y. B., S. C. Ho, & S. G. Chan. (2004). Identifying risk factors for low back pain (LBP) in

Chinese middle-aged women: a case-control study. *Health Care for Women*

Vingard, E., L. Alfredsson, M. Hagberg, A. Kilbom, T. Theorell, & M. Waldenstrom. (2000).

Wu, W. H., O. G. Meijer, K. Uegaki, J. M. Mens, J. H. van Dieen, P. I. Wuisman, & H. C.

Back pain is one of the most common complaints that brings patients to be examined by a physician (Moore, 2010). Pain may originate from a variety of tissues, including intervertebral disks, vertebrae, ligaments, neural structures, muscles, and fascia, or present as referred pain from adjacent pathology, such as peptic ulcers, pancreatitis, pyelonephritis, aortic aneurysm, and more (Henschke, et al., 2009). Nonspecific low back pain is typically managed with symptomatic care and physical therapy, with up to 90% of patients improving substantially over 3 months. It is such a common condition that the American College of Physicians has issued guidelines with a mandate against imaging patients for the first month after pain onset (Chou, 2010).

Serious, life-threatening diseases are uncommon causes of back pain; malignancy, ankylosing spondylitis, and infection together account for less than 5% of back pain cases in a typical primary care practice (Dagenais, et al., 2010). However, missing such a critical diagnosis represents a serious concern for every practitioner; thus complaints of back pain often lead to multiple imaging studies and consultations (Venkitaraman, et al., 2010).

The spine is one of the most common sites of metastasis with close to 20,000 cases of spine metastases arising each year in the United States (Sciubba, et al., 2009). The most common primary tumors in patients with metastases are breast, lung, prostate, and kidney cancer (Guillevin, et al., 2007). In close to 15% of oncology patients, the primary presenting symptoms of malignancy are related to spinal metastases. In these patients, the most common underlying pathology is lung cancer, followed by breast cancer in females and prostate cancer in male patients (Chamberlain & Kormanik, 1999).

When the patient's history is taken properly, a thorough physical examination is conducted, and appropriate diagnostic tests are performed, the physician can determine with a high level of accuracy whether an individual patient is suffering from nonspecific ("simple") back pain, or whether an underlying, potentially catastrophic disease is triggering the pain (Bach, et al., 1990).

Evaluation and Management of Lower Back Pain in Oncological Patients 93

A spinal mass can cause one of several forms of back pain. Localized pain is conned to the region of the spine affected by the tumor.  This pain is also typically worse at night and when the patient is recumbent, due to lengthening of the spine and distension of the spinal epidural venous plexus. This pain is often made worse by a Valsalva maneuver or other stretching movement of the spine or lower limb. The pain is usually dermatome-linked and may be associated with weakness of the muscles innervated by this nerve root (Cole & Patchell, 2008). If more than one nerve root is involved, the pain

A third type of pain appears when a pathologic fracture is present. This pain is generally focal, associated with instability, and progressive. It will worsen with movement. In the case of a fracture, the patient may remember a specific event or time when the pain began. It can be debilitating, necessitating the use of large doses of narcotics or preventing the patient from sitting or walking (Smith, 2011). These fractures may also lead to neurological changes

Sadly, not all patients with spinal metastasis present with early back pain. Many times a metastasis, like other slowly evolving conditions, becomes symptomatic only when there is neural compression. In this case, the patient will come to medical care only when there is cord compression, with imminent risk of losing mobility and control of the bowels. This late presentation is associated with a lower probability of neurological recovery, and a high rate

As is the case with any diagnostic process, the physical examination begins when the patient walks through the door. The patient's general appearance, nutritional state, walking pattern, and general habitus can be assessed during the walk to the examination bed. It is thus important for the physician to be positioned to watch the patient's entry, and to be alert to

A general examination should be performed, including clinical examination of the breasts, lungs, abdomen, thyroid, and prostate, in the appropriate setting. After the general examination, a thorough orthopedic examination should be performed to evaluate any limitation in movement or impairment due to metastatic disease in other locations. The spine should be examined to identify sites of focal tenderness and assess range of motion. Signs of spinal instability or neural compression should be evaluated, and a full neurological examination should be performed, including assessment of strength, deep and superficial sensation, and proprioception, as well as deep tendon and pathological reflexes (Winters, et al., 2006). In order to try to locate the specific location of the lesion, sensory and

Physical examination should be repeated periodically to allow early detection of any pathological motor or sensory findings or abnormal reflexes or any signs suggesting spinal

segment (Cole & Patchell, 2008).

might extend to more than one dermatome.

due to neural element compression (Shaw, et al., 1989).

of morbidity and mortality (Sundaresan, et al., 1995).

motor levels should be assessed and documented.

instability or pathological fracture (Bates & Reuler, 1988).

**2.3 Physical examination**

these details.

In taking the patient's history, one should try to define specific characteristics of the pain. Is this radicular or axial back pain? Is the pain worse at night or in the morning? Is the pain mechanical in nature or constant? Is it progressing? The examining physician should also look for signs and symptoms of systemic disease, such as fatigue, night sweats, weight loss, and changes in bowel habits. Personal habits such as smoking, alcohol consumption, or drug use should be identified as a potential clue to the underlying pathology.

In a patient with a known history of cancer, the situation is quite different. Each new ache and bump might lead to the fear of a metastasis, and patients will thus be highly sensitive to changes. On the other hand, ignoring symptoms or assuming that they are normal side effects of medical treatment may lead a missed diagnosis and delayed treatment, with the potential of significantly shortening a patient's life expectancy or greatly reducing the quality of remaining life (Verbeeck, 2004). Sadly, although the awareness to the risk of spinal metastases is high, even in patients at high risk, progression, with catastrophic consequences can occur during a drawn out diagnostic process (Cole & Patchell, 2008; Hagelberg & Allan, 1990; Loblaw, et al., 2005). Although a high level of suspicion may lead to higher rates of imaging in these patients, any back pain in a patient with a history of malignancy should be considered as suspicious for spinal metastases and should be fully investigated.

We aimed to review the essential skills required for diagnosis of the etiology of back pain, and to outline basic elements of treatment in patients presenting with metastatic disease to the spine.

### **2. Making the diagnosis**

#### **2.1 Characteristics of benign back pain**

Defining a patient's pain is a hard task. Pain is subjective. The way in which pain is experienced, tolerance for pain, the language used to describe it, and its impact on quality of life differ from patient to patient and from culture to culture. Pain can be affected by medications, comorbidities, prior treatments, and by the patient's life situation and mental state (Florence, 1981). With these points in mind, specific information can enable a skilled diagnostician to differentiate metastatic pain from benign back pain.

Benign back pain often arises from a specific event, is relieved by rest and lying down, and increases with activity such as lifting, sneezing, laughing, and the Valsalva maneuver (Lishchyna & Henderson, 2004). It is most commonly focal, with adjacent spasm of the lumbar muscles and buttocks. Benign back pain generally subsides several weeks after injury, and can be managed effectively with non-narcotic analgesics and physical therapy (Ladeira, 2011). Patients with benign pain may experience several relapses, but generally pain remits between attacks. In a portion of patients (up to 7%) benign pain becomes chronic, however a discussion of chronic back pain is beyond the scope of this chapter.

#### **2.2 Characteristics of metastatic back pain**

In contrast, pain caused by spinal metastases is typically persistent and progressive, and is not alleviated by rest. Often pain is worse at night, awakening the patient from sleep. This pain is typically focal at the level of the lesion, progresses over several days or weeks, and may be associated with neurological signs indicating pressure on the neural spinal elements (Bach, et al., 1990).

A spinal mass can cause one of several forms of back pain. Localized pain is conned to the region of the spine affected by the tumor. This type of pain presents when a metastasis that originally developed in the bone marrow extends to stretch the periosteum or invades soft tissues, triggering pain from the nerve roots or signaling instability in a specific spine segment (Cole & Patchell, 2008).

A second form of pain is radicular pain due to nerve root compression or invasion. This pain is also typically worse at night and when the patient is recumbent, due to lengthening of the spine and distension of the spinal epidural venous plexus. This pain is often made worse by a Valsalva maneuver or other stretching movement of the spine or lower limb. The pain is usually dermatome-linked and may be associated with weakness of the muscles innervated by this nerve root (Cole & Patchell, 2008). If more than one nerve root is involved, the pain might extend to more than one dermatome.

A third type of pain appears when a pathologic fracture is present. This pain is generally focal, associated with instability, and progressive. It will worsen with movement. In the case of a fracture, the patient may remember a specific event or time when the pain began. It can be debilitating, necessitating the use of large doses of narcotics or preventing the patient from sitting or walking (Smith, 2011). These fractures may also lead to neurological changes due to neural element compression (Shaw, et al., 1989).

Sadly, not all patients with spinal metastasis present with early back pain. Many times a metastasis, like other slowly evolving conditions, becomes symptomatic only when there is neural compression. In this case, the patient will come to medical care only when there is cord compression, with imminent risk of losing mobility and control of the bowels. This late presentation is associated with a lower probability of neurological recovery, and a high rate of morbidity and mortality (Sundaresan, et al., 1995).

#### **2.3 Physical examination**

92 Low Back Pain Pathogenesis and Treatment

In taking the patient's history, one should try to define specific characteristics of the pain. Is this radicular or axial back pain? Is the pain worse at night or in the morning? Is the pain mechanical in nature or constant? Is it progressing? The examining physician should also look for signs and symptoms of systemic disease, such as fatigue, night sweats, weight loss, and changes in bowel habits. Personal habits such as smoking, alcohol consumption, or

In a patient with a known history of cancer, the situation is quite different. Each new ache and bump might lead to the fear of a metastasis, and patients will thus be highly sensitive to changes. On the other hand, ignoring symptoms or assuming that they are normal side effects of medical treatment may lead a missed diagnosis and delayed treatment, with the potential of significantly shortening a patient's life expectancy or greatly reducing the quality of remaining life (Verbeeck, 2004). Sadly, although the awareness to the risk of spinal metastases is high, even in patients at high risk, progression, with catastrophic consequences can occur during a drawn out diagnostic process (Cole & Patchell, 2008; Hagelberg & Allan, 1990; Loblaw, et al., 2005). Although a high level of suspicion may lead to higher rates of imaging in these patients, any back pain in a patient with a history of malignancy should be

We aimed to review the essential skills required for diagnosis of the etiology of back pain, and to outline basic elements of treatment in patients presenting with metastatic disease to

Defining a patient's pain is a hard task. Pain is subjective. The way in which pain is experienced, tolerance for pain, the language used to describe it, and its impact on quality of life differ from patient to patient and from culture to culture. Pain can be affected by medications, comorbidities, prior treatments, and by the patient's life situation and mental state (Florence, 1981). With these points in mind, specific information can enable a skilled

Benign back pain often arises from a specific event, is relieved by rest and lying down, and increases with activity such as lifting, sneezing, laughing, and the Valsalva maneuver (Lishchyna & Henderson, 2004). It is most commonly focal, with adjacent spasm of the lumbar muscles and buttocks. Benign back pain generally subsides several weeks after injury, and can be managed effectively with non-narcotic analgesics and physical therapy (Ladeira, 2011). Patients with benign pain may experience several relapses, but generally pain remits between attacks. In a portion of patients (up to 7%) benign pain becomes chronic, however a discussion of chronic back pain is beyond the scope of this chapter.

In contrast, pain caused by spinal metastases is typically persistent and progressive, and is not alleviated by rest. Often pain is worse at night, awakening the patient from sleep. This pain is typically focal at the level of the lesion, progresses over several days or weeks, and may be associated with neurological signs indicating pressure on the neural spinal elements

drug use should be identified as a potential clue to the underlying pathology.

considered as suspicious for spinal metastases and should be fully investigated.

diagnostician to differentiate metastatic pain from benign back pain.

the spine.

**2. Making the diagnosis**

**2.1 Characteristics of benign back pain**

**2.2 Characteristics of metastatic back pain**

(Bach, et al., 1990).

As is the case with any diagnostic process, the physical examination begins when the patient walks through the door. The patient's general appearance, nutritional state, walking pattern, and general habitus can be assessed during the walk to the examination bed. It is thus important for the physician to be positioned to watch the patient's entry, and to be alert to these details.

A general examination should be performed, including clinical examination of the breasts, lungs, abdomen, thyroid, and prostate, in the appropriate setting. After the general examination, a thorough orthopedic examination should be performed to evaluate any limitation in movement or impairment due to metastatic disease in other locations. The spine should be examined to identify sites of focal tenderness and assess range of motion. Signs of spinal instability or neural compression should be evaluated, and a full neurological examination should be performed, including assessment of strength, deep and superficial sensation, and proprioception, as well as deep tendon and pathological reflexes (Winters, et al., 2006). In order to try to locate the specific location of the lesion, sensory and motor levels should be assessed and documented.

Physical examination should be repeated periodically to allow early detection of any pathological motor or sensory findings or abnormal reflexes or any signs suggesting spinal instability or pathological fracture (Bates & Reuler, 1988).

Evaluation and Management of Lower Back Pain in Oncological Patients 95

sclerotic, and mixed lesions are depicted well on CT scans, as are lesions involving the viscera and vascular anatomy. However, while 16/64 row MDCT provides excellent image quality and clear assessment of bony structures, metastatic lesions without significant bone destruction may be missed (Buhmann-Kirchhoff, et al., 2009). CT scans are also associated with relatively high quantities of radiation, limiting the number of screening studies that should be performed, especially in a younger population (Huda & He, 2011). In addition, the differential diagnosis between a malignant process versus osteoporotic or degenerative disease can be challenging in the spinal column (Chassang, et al., 2007). CT findings that suggest metastatic disease include destruction of the anterolateral or posterior vertebral cortex, destruction of one or both pedicles, an epidural mass, and presence of a focal

paraspinal soft tissue mass (Fehlings & Rao, 2000; Laredo, et al., 1995).

A B C

after surgery she was treated with adjuvant EBRT.

Fig. 1. **Spinal metastasis to the thoracic and lumbar spine.** A 74-year-old female with a history of gastrointestinal stromal tumor (GIST) presented with right leg sciatic pain and weakness. **(A)** Sagittal CT revealed an osteolytic metastasis in the vertebral body of T7, L1, and L2 (arrows). The L2 metastasis was most prominent, producing compression of the cauda equina. **(B)** Axial CT through the body of L2 demonstrating the soft tissue mass, which has created a cavity in the vertebral body, narrowed the spinal canal and created pressure on the cauda equina. **(C)** X-ray after transpedicular excision of the lesion shows reconstruction of the vertebral body with polymethylmethacrylate (PMMA) and L1-L3 posterolateral fixation with transpedicular screws and rods. The patient experienced immediate and sustained pain relief, with recovery of her previous strength. Two weeks

With findings from the physical examination in hand, the physician should have an understanding of the pathology, and whether it is pointing towards metastatic spread of the primary disease to the spine. The next steps in diagnosis or treatment are determined by these findings.

#### **2.4 Blood work**

If the history and physical examination leads to the suspicion that the patient's pain could originate from something more severe than common backache, blood work is mandated.  If laboratory studies reveal anemia, thrombocytopenia hypercalcaemia, or elevated levels of alkaline phosphatase, concern should increase (Nieder, et al., 2010). Specific markers for prostate and breast cancer should be tested, as well as urine and blood protein electrophoresis if gammopathy (multiple myeloma or plasmacytoma) is suspected (Scharschmidt, et al., 2011).

A blood smear or a bone marrow biopsy may be indicated if hematological disease is suspected (Raje & Roodman, 2011).

#### **2.5 Imaging**

Metastases generally appear in more than one anatomic location. They can be in the brain, soft liver, lungs, or lymph nodes. In the skeleton, the third most common location for tumor spread, lesions may be found in the vertebrae, pelvis, proximal parts of the femur, ribs, proximal part of the humerus, and skull (Ratanatharathorn, et al., 1999). If a spinal metastasis is suspected, it is important to perform a full workup, both to identify the primary lesion and to detect other metastases.

#### **2.5.1 X-ray**

Simple X-rays of the spine are considered to be the first and most attainable imaging study. If obtained, they should be complimented with a chest X-ray for a preliminary search for lung involvement, however neither spinal nor lung tumors are well visualized on radiographs until the malignancy has advanced significantly (Nielsen, et al., 1991). Lateral X-ray may show vertebral body collapse. AP views may demonstrate pedicle erosion (the "winking owl" sign) or evidence of a paraspinal mass (Fehlings & Rao, 2000).

In cases where the physician has a high degree of suspicion towards metastatic spine disease, a more expeditious approach to diagnosis should be taken using advance imaging techniques such as CT or MRI (Black, et al., 1996). In these patients X-ray may be used as a complimentary study, since images obtained standing and dynamic X-rays can provide a better understanding of sagittal balance and stability of the diseased spine.

#### **2.5.2 Computed Tomography**

Computerized tomography (CT) has higher sensitivity and specificity than X-ray. Multislice CT (MDCT) systems facilitate a single rapid study of the chest-abdomen-pelvis. Osteolytic,

With findings from the physical examination in hand, the physician should have an understanding of the pathology, and whether it is pointing towards metastatic spread of the primary disease to the spine. The next steps in diagnosis or treatment are determined by

If the history and physical examination leads to the suspicion that the patient's pain could originate from something more severe than common backache, blood work is mandated.  If laboratory studies reveal anemia, thrombocytopenia hypercalcaemia, or elevated levels of alkaline phosphatase, concern should increase (Nieder, et al., 2010). Specific markers for prostate and breast cancer should be tested, as well as urine and blood protein electrophoresis if gammopathy (multiple myeloma or plasmacytoma) is suspected

A blood smear or a bone marrow biopsy may be indicated if hematological disease is

Metastases generally appear in more than one anatomic location. They can be in the brain, soft liver, lungs, or lymph nodes. In the skeleton, the third most common location for tumor spread, lesions may be found in the vertebrae, pelvis, proximal parts of the femur, ribs, proximal part of the humerus, and skull (Ratanatharathorn, et al., 1999). If a spinal metastasis is suspected, it is important to perform a full workup, both to identify the

Simple X-rays of the spine are considered to be the first and most attainable imaging study. If obtained, they should be complimented with a chest X-ray for a preliminary search for lung involvement, however neither spinal nor lung tumors are well visualized on radiographs until the malignancy has advanced significantly (Nielsen, et al., 1991). Lateral X-ray may show vertebral body collapse. AP views may demonstrate pedicle erosion (the

In cases where the physician has a high degree of suspicion towards metastatic spine disease, a more expeditious approach to diagnosis should be taken using advance imaging techniques such as CT or MRI (Black, et al., 1996). In these patients X-ray may be used as a complimentary study, since images obtained standing and dynamic X-rays can provide a

Computerized tomography (CT) has higher sensitivity and specificity than X-ray. Multislice CT (MDCT) systems facilitate a single rapid study of the chest-abdomen-pelvis. Osteolytic,

"winking owl" sign) or evidence of a paraspinal mass (Fehlings & Rao, 2000).

better understanding of sagittal balance and stability of the diseased spine.

these findings.

**2.4 Blood work**

(Scharschmidt, et al., 2011).

**2.5 Imaging**

**2.5.1 X-ray**

suspected (Raje & Roodman, 2011).

**2.5.2 Computed Tomography**

primary lesion and to detect other metastases.

sclerotic, and mixed lesions are depicted well on CT scans, as are lesions involving the viscera and vascular anatomy. However, while 16/64 row MDCT provides excellent image quality and clear assessment of bony structures, metastatic lesions without significant bone destruction may be missed (Buhmann-Kirchhoff, et al., 2009). CT scans are also associated with relatively high quantities of radiation, limiting the number of screening studies that should be performed, especially in a younger population (Huda & He, 2011). In addition, the differential diagnosis between a malignant process versus osteoporotic or degenerative disease can be challenging in the spinal column (Chassang, et al., 2007). CT findings that suggest metastatic disease include destruction of the anterolateral or posterior vertebral cortex, destruction of one or both pedicles, an epidural mass, and presence of a focal paraspinal soft tissue mass (Fehlings & Rao, 2000; Laredo, et al., 1995).

Fig. 1. **Spinal metastasis to the thoracic and lumbar spine.** A 74-year-old female with a history of gastrointestinal stromal tumor (GIST) presented with right leg sciatic pain and weakness. **(A)** Sagittal CT revealed an osteolytic metastasis in the vertebral body of T7, L1, and L2 (arrows). The L2 metastasis was most prominent, producing compression of the cauda equina. **(B)** Axial CT through the body of L2 demonstrating the soft tissue mass, which has created a cavity in the vertebral body, narrowed the spinal canal and created pressure on the cauda equina. **(C)** X-ray after transpedicular excision of the lesion shows reconstruction of the vertebral body with polymethylmethacrylate (PMMA) and L1-L3 posterolateral fixation with transpedicular screws and rods. The patient experienced immediate and sustained pain relief, with recovery of her previous strength. Two weeks after surgery she was treated with adjuvant EBRT.

Evaluation and Management of Lower Back Pain in Oncological Patients 97

With the exception of purely lytic tumors such as myeloma, eosinophilic granuloma, and renal cell carcinoma, 99mTc-methylene diphosphonate (MDP) bone scan has good sensitivity to tumors, is widely available, and has a relatively low cost, with the ability to scan the entire skeleton in a single study. It can be performed as a flat two dimensional exam or, incorporating more advanced single-photon emission computed tomography (SPECT) technology, with true 3D information. Bone scans have moderate sensitivity in the spine and pelvis (Steinborn, et al., 1999). Sensitivity to detection of spine metastasis can be significantly improved by the combination of bone scan and SPECT imaging capabilities (Schirrmeister, et al., 2001). Bone scans combined with SPECT may depict spinal lesions as well as metastases in other bones or organs, and provide some indication of the site of the primary tumor in cases where this is not known. The main drawback to these studies is exposure to high levels of ionizing radiation and a lower rate of detection when compared

FDG-PET/CT studies in oncology utilize labeled glucose with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), in combination with MDCT, to provide the benefits of metabolic and anatomic imaging in a single study. FDG is a glucose analog that is taken up by glucoseusing cells and phosphorylated by hexokinase in the mitochondria. Increased tumor [18F]- FDG uptake is depicted by positron emission tomography (PET), although proliferative activity is also broadly related to the number of viable tumor cells. When glucose is metabolized, the tissue incorporates the radioactive isomer, increasing local particle emission and producing a high intensity signal on PET/CT images (Young, et al., 1999).

PET-CT is a sensitive method for assessment of bone and bone marrow metastases, as well as vertebral and extravertebral skeletal masses. It is sensitive for osteolytic and osteoblastic metastasis and depicts early malignant bone-marrow infiltration (Kruger, et al., 2009). It provides precise localization and is sensitive to accompanying soft tissue metastases in the lung, liver, lymphatic system, and elsewhere (Metser, et al., 2004; Nguyen, et al., 2007). Low resolution PET scans are combined with the high resolution of thin slice CT, for exquisite depiction of even small metastases in early stages. PET/CT has higher sensitivity and specificity compared to bone scintigraphy or CT in the detection of skeletal metastases (Kruger, et al., 2009), however the rate of false-positive findings that require follow-up

Discussions of metastatic epidural cord compression usually focus on the thoracic spine. Although the spinal cord usually ends in the lumbar spine between L1 and L2 in adults, up to 20% of metastatic cord compression occurs at these levels; thus lumbar cord compression

Metastatic spinal cord compression (SCC) occurs in 5–10% of patients with cancer (Bach, et al., 1990). It is a true emergency, because delay in diagnosis and treatment may result in permanent neurological impairment. SCC is caused by direct compression of metastasis or primary tumors invading the vertebral bodies, breaking through the cortex, and

imaging with other modalities is also higher (Kuo & Cheng, 2005).

**2.5.4 99Tc bone scan**

with MRI (Sedonja & Budihna, 1999).

**2.5.5 PET/CT**

**3. Cord compression**

must also be discussed.

#### **2.5.3 Magnetic Resonance Imaging**

Magnetic resonance imaging (MRI) is gold standard for evaluating spinal tumors. It depicts vertebral bone marrow infiltration by tumor cells as well as soft tissue masses in and around the spinal column. Bone marrow invaded by a neoplasm is characterized by increased cellularity, resulting in a decreased signal on T1-weighted images and a high signal on T2 weighted images, thus differentiating it from normal marrow tissue (Loblaw, et al., 2005). Intravenous gadolinium further increases the contrast between tumor and normal tissues (Loughrey, et al., 2000). MRI has been shown to detect up to 98.5% of vertebrae with metastatic disease, including both osteolyitic and osteoblastic lesions. This high level of detection is not compromised by osteoporosity (Buhmann-Kirchhoff, et al., 2009).

However, MRI is a costly, time consuming exam, limiting its efficacy in patients who have difficulty lying down without moving for long periods of time and those who are claustrophobic or morbid (Eshed, et al., 2007). In addition, it may be difficult to differentiate between osteoporotic compression fracture and metastatic disease, especially if a fracture co-exists. Signs that characterize malignant vertebral collapse include ill-defined vertebral margins, abnormal signal involvement of the pedicle, a marked and heterogeneous MR enhancement pattern, and the presence of an irregular nodular-type paraspinal vertebral lesion (Shih, et al., 1999). Using of different diffusion coefficients may assist correctly identifying this deferential diagnosis (Chan, et al., 2002).

Fig. 2. **MRI of the lumbar spine.** A 42-year-old male presented with cauda equina syndrome due to an epidural metastasis to the lumbar spine from a synovial sarcoma originating in the left lower limb. **(A)** Preoperative T2-weighted sagittal MRI demonstrating a metastasis to the L4 vertebral body invading the epidural space and compressing the thecal sac (arrow). The patient underwent laminectomy and resection of the epidural mass. (B) Postoperative T2-weighted sagittal MRI showing post-laminectomy decompression of the thecal sac.

#### **2.5.4 99Tc bone scan**

96 Low Back Pain Pathogenesis and Treatment

Magnetic resonance imaging (MRI) is gold standard for evaluating spinal tumors. It depicts vertebral bone marrow infiltration by tumor cells as well as soft tissue masses in and around the spinal column. Bone marrow invaded by a neoplasm is characterized by increased cellularity, resulting in a decreased signal on T1-weighted images and a high signal on T2 weighted images, thus differentiating it from normal marrow tissue (Loblaw, et al., 2005). Intravenous gadolinium further increases the contrast between tumor and normal tissues (Loughrey, et al., 2000). MRI has been shown to detect up to 98.5% of vertebrae with metastatic disease, including both osteolyitic and osteoblastic lesions. This high level of

However, MRI is a costly, time consuming exam, limiting its efficacy in patients who have difficulty lying down without moving for long periods of time and those who are claustrophobic or morbid (Eshed, et al., 2007). In addition, it may be difficult to differentiate between osteoporotic compression fracture and metastatic disease, especially if a fracture co-exists. Signs that characterize malignant vertebral collapse include ill-defined vertebral margins, abnormal signal involvement of the pedicle, a marked and heterogeneous MR enhancement pattern, and the presence of an irregular nodular-type paraspinal vertebral lesion (Shih, et al., 1999). Using of different diffusion coefficients may assist correctly

detection is not compromised by osteoporosity (Buhmann-Kirchhoff, et al., 2009).

identifying this deferential diagnosis (Chan, et al., 2002).

A B

the thecal sac.

Fig. 2. **MRI of the lumbar spine.** A 42-year-old male presented with cauda equina syndrome due to an epidural metastasis to the lumbar spine from a synovial sarcoma originating in the left lower limb. **(A)** Preoperative T2-weighted sagittal MRI demonstrating a metastasis to the L4 vertebral body invading the epidural space and compressing the thecal sac (arrow). The patient underwent laminectomy and resection of the epidural mass. (B) Postoperative T2-weighted sagittal MRI showing post-laminectomy decompression of

**2.5.3 Magnetic Resonance Imaging**

With the exception of purely lytic tumors such as myeloma, eosinophilic granuloma, and renal cell carcinoma, 99mTc-methylene diphosphonate (MDP) bone scan has good sensitivity to tumors, is widely available, and has a relatively low cost, with the ability to scan the entire skeleton in a single study. It can be performed as a flat two dimensional exam or, incorporating more advanced single-photon emission computed tomography (SPECT) technology, with true 3D information. Bone scans have moderate sensitivity in the spine and pelvis (Steinborn, et al., 1999). Sensitivity to detection of spine metastasis can be significantly improved by the combination of bone scan and SPECT imaging capabilities (Schirrmeister, et al., 2001). Bone scans combined with SPECT may depict spinal lesions as well as metastases in other bones or organs, and provide some indication of the site of the primary tumor in cases where this is not known. The main drawback to these studies is exposure to high levels of ionizing radiation and a lower rate of detection when compared with MRI (Sedonja & Budihna, 1999).

#### **2.5.5 PET/CT**

FDG-PET/CT studies in oncology utilize labeled glucose with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), in combination with MDCT, to provide the benefits of metabolic and anatomic imaging in a single study. FDG is a glucose analog that is taken up by glucoseusing cells and phosphorylated by hexokinase in the mitochondria. Increased tumor [18F]- FDG uptake is depicted by positron emission tomography (PET), although proliferative activity is also broadly related to the number of viable tumor cells. When glucose is metabolized, the tissue incorporates the radioactive isomer, increasing local particle emission and producing a high intensity signal on PET/CT images (Young, et al., 1999).

PET-CT is a sensitive method for assessment of bone and bone marrow metastases, as well as vertebral and extravertebral skeletal masses. It is sensitive for osteolytic and osteoblastic metastasis and depicts early malignant bone-marrow infiltration (Kruger, et al., 2009). It provides precise localization and is sensitive to accompanying soft tissue metastases in the lung, liver, lymphatic system, and elsewhere (Metser, et al., 2004; Nguyen, et al., 2007). Low resolution PET scans are combined with the high resolution of thin slice CT, for exquisite depiction of even small metastases in early stages. PET/CT has higher sensitivity and specificity compared to bone scintigraphy or CT in the detection of skeletal metastases (Kruger, et al., 2009), however the rate of false-positive findings that require follow-up imaging with other modalities is also higher (Kuo & Cheng, 2005).

#### **3. Cord compression**

Discussions of metastatic epidural cord compression usually focus on the thoracic spine. Although the spinal cord usually ends in the lumbar spine between L1 and L2 in adults, up to 20% of metastatic cord compression occurs at these levels; thus lumbar cord compression must also be discussed.

Metastatic spinal cord compression (SCC) occurs in 5–10% of patients with cancer (Bach, et al., 1990). It is a true emergency, because delay in diagnosis and treatment may result in permanent neurological impairment. SCC is caused by direct compression of metastasis or primary tumors invading the vertebral bodies, breaking through the cortex, and

Evaluation and Management of Lower Back Pain in Oncological Patients 99

stimulant plus stool softener should be initiated to prevent constipation from opioid use. Care must be taken to avoid misuse and abuse of opioids, even in cancer patients

Adjunct agents such as anticonvulsants (e.g., gabapentin, lamotrigine, topiramate), tricyclic antidepressants (e.g., amitriptyline, imipramine, desipramine, nortriptyline), venlafaxine, duloxetine, or topical analgesics (e.g., lidocaine or capsaicin) may also help to reduce

In cases of breakthough pain, oral transmucosal fentanyl and transdermal patches have been shown to be an effective treatment for pain including sharp pain episodes, yielding a more rapid onset of relief. In cases where patients developed tolerance towards opioid narcotics, the use of anesthetics, such as ketamine can provide adequate pain relief (Chazan, et al.,

The use of cannabinoids as an alternative or to augment narcotics has become popular, primarily for light-to-intermediate pain. Three cannabinoids, all a combination of the delta-9-tetra-hydrocannabinol and cannabidiol cannabinoids from the *Cannabis sativa* plant, are available on the market. Sativex, a cannabinoid medication, has recently received approval as an adjuvant medication for the treatment of cancer pain in North America. It is a sublingual (mouth) spray that can be titrated up to the most effective dose (Bonneau, 2008). Other forms of cannabinoids treatment include smoking marijuana, or ingestion of oils or even cookies with insertion of active cannabinoid components. In our experience, "cannabis cookies" have provided relief or reduction in chronic pain levels for some cancer patients. The use of cannabinoids is indicated in cancer pain with a neuropathic component that is not adequately controlled with opioids. Cannabinoids are not suitable as a single medication

Steroids are commonly prescribed in patients with metastatic bone disease. Steroids reduce edema and have been shown to reduce the size of metastases from tumors of hematological origin, and occasionally breast cancer (Cole & Patchell, 2008). They have also been shown to have a rapid analgesic effect (Bonneau, 2008). However, they are associated with side effects, such as wound dehiscence, gastric ulcers, rectal bleeding, psychosis, and diabetes

An early study (Greenberg, et al., 1980) demonstrated quick and significant pain reduction in patients treated with steroids. A subsequent randomized trial (Vecht, et al., 1989) compared the effect of 10 mg IV dexamethasone versus 100 mg IV followed by 16 mg daily orally and found no differences between the conventional and high-dose group on pain, ambulation, or bladder function. Both the conventional and high-dose regimens provided

A randomized, controlled trial (Sorensen, et al., 1994) studied the administration of 96 mg of IV dexamethasone followed by 96 mg orally for 3 days and then tapered in 10 days, with subsequent radiotherapy, versus radiotherapy as a single modality in the treatment of SCC. Steroid treatment provided a statistically significant improvement in ambulation at 3 to 6 months, albeit with increased side effects, including psychoses and gastric ulcers requiring

mellitus, and may increase susceptibility to infections (Shih & Jackson, 2007).

surgery. The effect of dexamethasone on pain reduction was not addressed.

neuropathic pain caused by nerve compression (Hitron & Adams, 2009).

(Manchikanti, et al., 2010).

2008).

in spine metastasis.

significant pain relief.

**4.2 Steroids**

compressing the vertebral canal and nerve roots (Bilsky, et al., 2000). The most commonly affected site is the thoracic spine, which is also the area in which the canal is the tightest, leaving little space for movement of the cord. Breast cancer is the most frequent primary malignancy associated with SCC, followed by lung, prostate, and renal cancers (Byrne, 1992). However, SCC is also common in patients with hematological tumors such as lymphoma and myeloma. SCC is the initial manifestation of a metastatic spread of a tumor in approximately 20% of cancer patients; in patients with lung cancer the rate of SCC at first presentation climbs to 30% (Chahal, et al., 2003). In most of the cases of SCC, back pain has been present for several months before detection, but was ignored by the patient and caretakers (Byrne, 1992).

The most important factor in determining the post-treatment outcome is pretreatment ambulatory function of the patient. Late presentation with neurological deficits, including bowel or bladder dysfunction, is often associated with irreversible paraplegia. In recent series, 74-100% of patients who were ambulatory before surgery retained the ability to walk after decompression, and 57-82% of nonambulatory patients regained ambulation (Bilsky, et al., 2009). However ambulation at surgery remains a key determinant of outcome, therefore, urgent investigations must be performed to facilitate treatment before function is lost.

#### **4. Treatment**

#### **4.1 Medical management of pain**

Basic pain control is achieved by the use of narcotics and non-narcotic analgesics. In patients with back pain due to metastases, pain control is one of the most important goals in management, as the life expectancy of the patients is limited (Padalkar & Tow, 2011). Sadly, despite this concept, most patients are undertreated for pain, which causes a significant reduction in quality of life (Cleeland, 2006). Two types of pain needed to be addressed when dealing with medical management of the metastatic patients, the constant pain of the metastasis and an acute episode of sharp pain, known as "breakthrough pain" (Lipton, 2011).

The first line of treatment in patients with mild low back pain is the use of nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen. These agents may provide adequate pain relief. There have been nine trials indicating that the use of NSAIDS provides pain relief in bone metastasis, including one showing that NSAIDS (specifically COX-2 inhibitors) assist in tumor control as well (Smith, 2011). Acetaminophen is preferred in patients with thrombocytopenia, renal dysfunction, those receiving nephrotoxic agents, and those at risk for gastrointestinal bleeding. In patients with liver dysfunction, NSAIDs are preferred for mild pain (Hitron & Adams, 2009)

In patients who need the next level of treatment for their low back pain, opioid therapy should be added. Common protocols begin with low doses of immediate-release shortacting agents (i.e. morphine), with reassessment for the level of effect every 1 to 2 hours. After 24 hours of pain control on a short-acting regimen, patients should be converted to a long-acting agent such as sustained-release morphine, oxycodone, fentanyl, or methadone for basal control. Patients who are opioid tolerant should begin with higher doses of shortacting agents, with the higher dose compensating for shorter duration of effect. If a patient is already using a long-acting product, this should be continued. A bowel regimen with a stimulant plus stool softener should be initiated to prevent constipation from opioid use. Care must be taken to avoid misuse and abuse of opioids, even in cancer patients (Manchikanti, et al., 2010).

Adjunct agents such as anticonvulsants (e.g., gabapentin, lamotrigine, topiramate), tricyclic antidepressants (e.g., amitriptyline, imipramine, desipramine, nortriptyline), venlafaxine, duloxetine, or topical analgesics (e.g., lidocaine or capsaicin) may also help to reduce neuropathic pain caused by nerve compression (Hitron & Adams, 2009).

In cases of breakthough pain, oral transmucosal fentanyl and transdermal patches have been shown to be an effective treatment for pain including sharp pain episodes, yielding a more rapid onset of relief. In cases where patients developed tolerance towards opioid narcotics, the use of anesthetics, such as ketamine can provide adequate pain relief (Chazan, et al., 2008).

The use of cannabinoids as an alternative or to augment narcotics has become popular, primarily for light-to-intermediate pain. Three cannabinoids, all a combination of the delta-9-tetra-hydrocannabinol and cannabidiol cannabinoids from the *Cannabis sativa* plant, are available on the market. Sativex, a cannabinoid medication, has recently received approval as an adjuvant medication for the treatment of cancer pain in North America. It is a sublingual (mouth) spray that can be titrated up to the most effective dose (Bonneau, 2008). Other forms of cannabinoids treatment include smoking marijuana, or ingestion of oils or even cookies with insertion of active cannabinoid components. In our experience, "cannabis cookies" have provided relief or reduction in chronic pain levels for some cancer patients. The use of cannabinoids is indicated in cancer pain with a neuropathic component that is not adequately controlled with opioids. Cannabinoids are not suitable as a single medication in spine metastasis.

#### **4.2 Steroids**

98 Low Back Pain Pathogenesis and Treatment

compressing the vertebral canal and nerve roots (Bilsky, et al., 2000). The most commonly affected site is the thoracic spine, which is also the area in which the canal is the tightest, leaving little space for movement of the cord. Breast cancer is the most frequent primary malignancy associated with SCC, followed by lung, prostate, and renal cancers (Byrne, 1992). However, SCC is also common in patients with hematological tumors such as lymphoma and myeloma. SCC is the initial manifestation of a metastatic spread of a tumor in approximately 20% of cancer patients; in patients with lung cancer the rate of SCC at first presentation climbs to 30% (Chahal, et al., 2003). In most of the cases of SCC, back pain has been present for several months before detection, but was ignored by the patient and

The most important factor in determining the post-treatment outcome is pretreatment ambulatory function of the patient. Late presentation with neurological deficits, including bowel or bladder dysfunction, is often associated with irreversible paraplegia. In recent series, 74-100% of patients who were ambulatory before surgery retained the ability to walk after decompression, and 57-82% of nonambulatory patients regained ambulation (Bilsky, et al., 2009). However ambulation at surgery remains a key determinant of outcome, therefore, urgent investigations must be performed to facilitate treatment before function is lost.

Basic pain control is achieved by the use of narcotics and non-narcotic analgesics. In patients with back pain due to metastases, pain control is one of the most important goals in management, as the life expectancy of the patients is limited (Padalkar & Tow, 2011). Sadly, despite this concept, most patients are undertreated for pain, which causes a significant reduction in quality of life (Cleeland, 2006). Two types of pain needed to be addressed when dealing with medical management of the metastatic patients, the constant pain of the metastasis and an acute episode of sharp pain, known as "breakthrough pain" (Lipton,

The first line of treatment in patients with mild low back pain is the use of nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen. These agents may provide adequate pain relief. There have been nine trials indicating that the use of NSAIDS provides pain relief in bone metastasis, including one showing that NSAIDS (specifically COX-2 inhibitors) assist in tumor control as well (Smith, 2011). Acetaminophen is preferred in patients with thrombocytopenia, renal dysfunction, those receiving nephrotoxic agents, and those at risk for gastrointestinal bleeding. In patients with liver dysfunction, NSAIDs are preferred for

In patients who need the next level of treatment for their low back pain, opioid therapy should be added. Common protocols begin with low doses of immediate-release shortacting agents (i.e. morphine), with reassessment for the level of effect every 1 to 2 hours. After 24 hours of pain control on a short-acting regimen, patients should be converted to a long-acting agent such as sustained-release morphine, oxycodone, fentanyl, or methadone for basal control. Patients who are opioid tolerant should begin with higher doses of shortacting agents, with the higher dose compensating for shorter duration of effect. If a patient is already using a long-acting product, this should be continued. A bowel regimen with a

caretakers (Byrne, 1992).

**4. Treatment**

2011).

**4.1 Medical management of pain**

mild pain (Hitron & Adams, 2009)

Steroids are commonly prescribed in patients with metastatic bone disease. Steroids reduce edema and have been shown to reduce the size of metastases from tumors of hematological origin, and occasionally breast cancer (Cole & Patchell, 2008). They have also been shown to have a rapid analgesic effect (Bonneau, 2008). However, they are associated with side effects, such as wound dehiscence, gastric ulcers, rectal bleeding, psychosis, and diabetes mellitus, and may increase susceptibility to infections (Shih & Jackson, 2007).

An early study (Greenberg, et al., 1980) demonstrated quick and significant pain reduction in patients treated with steroids. A subsequent randomized trial (Vecht, et al., 1989) compared the effect of 10 mg IV dexamethasone versus 100 mg IV followed by 16 mg daily orally and found no differences between the conventional and high-dose group on pain, ambulation, or bladder function. Both the conventional and high-dose regimens provided significant pain relief.

A randomized, controlled trial (Sorensen, et al., 1994) studied the administration of 96 mg of IV dexamethasone followed by 96 mg orally for 3 days and then tapered in 10 days, with subsequent radiotherapy, versus radiotherapy as a single modality in the treatment of SCC. Steroid treatment provided a statistically significant improvement in ambulation at 3 to 6 months, albeit with increased side effects, including psychoses and gastric ulcers requiring surgery. The effect of dexamethasone on pain reduction was not addressed.

Evaluation and Management of Lower Back Pain in Oncological Patients 101

Hoy et al showed that many patients experience pain relief with chemotherapy, even in cases where there is no objective tumor response (Hoy, 1989). Although palliative, the exact benefit of chemotherapy is difficult to measure. Potential indications for palliative chemotherapy include symptoms due to metastatic disease, hypercalcemia, bone marrow infiltration, and clinical conditions known to be associated with bone or spine metastases. As patients are mainly treated with a combination of therapies, the exact effect of the

In tumors that react quickly to chemotherapy, as in testicular cancers, lymphoma, or myeloma, administration of chemotherapy can have a pronounced effect in reducing back pain (Samoladas, et al., 2008). In tumors where the response to chemotherapy is slower, as in pancreatic cancer, pain reduction parallels the decrease in pressure exerted on spinal structures as the tumor slowly diminishes in size (Takuma, et al., 2006). However, in very advanced cancer patients there is little justification for using chemotherapy because of its

Hormonal therapy, based on the principle of depriving tumor cells of the growth stimulus induced by hormones that change the hormonal environment, may be beneficial in breast, prostate, and endometrial cancers (Wood, 1993). This treatment has a lower toxicity profile compared to chemotherapy, and should be the first therapeutic modality if possible. Dearnaley showed that hormonal therapy provides sustained symptom relief in patients with widespread painful bone metastases from prostatic cancer (Dearnaley, 1994). Cresenda et al showed that the combination of hormonal therapy with radiation for spinal metastasis reduces pain in 77% of patients (Cereceda, et al., 2003). There are no data regarding the impact on pain from the isolated use of hormonal therapy in patients with spinal metastasis.

Radiotherapy has served as a cornerstone for the treatment of bone metastases since it was introduced in the 1950s. Its benefits include reduction of pain and neurological complications arising from spinal cord compression. Radiation-based treatment is undergoing a revolution, with new stereotactic techniques for single-shot or fractionated treatment showing good results. However the mainstay of radiation-based treatment is external beam radiation therapy (EBRT) (Cole & Patchell, 2008; Harel & Angelov, 2010).

The exact pathophysiology of tumor response to radiotherapy is not fully understood, however EBRT can lead to rapid reduction in the tumor size, sometimes within 24 hours, decreasing local periosteal nerve stimulation. EBRT is typically given from a posterior field to the affected vertebra(e), with radiation delivered to a treatment area including one vertebral body above and one below to compensate for daily variations in patient setup.

A meta-analysis (Agarawal, et al., 2006), reported that over 40% of patients with bone metastases treated with radiation achieved at least a 50% reduction in pain, however fewer

In cases of SCC, when surgery is not performed, the use of radiation combined with steroids has been shown to provide improved pain management and improved outcome when

response in the bone is more difficult to assess (Lote, et al., 1986).

toxicity (Bruera, 1993).

**4.5 Radiation-based treatment**

**4.5.1 External beam radiation therapy**

than 30% experienced complete pain relief at 1 month.

Currently there are no absolute guidelines for steroid treatment in patients with back pain due to spinal metastases. The decision of whether to treat, as well as steroid dose are determined by the treating physician. In cases of SCC, steroid treatment is given as an adjuvant to surgery or to chemo- or radiotherapy, and not as sole treatment modality.

#### **4.3 Bisphosphonates**

Bisphosphonates are pyrophosphate analogues. The bisphosphonates strongly bind hydroxyapatite crystals in bone, preventing the creation of the ruffle border of the osteoclasts that prevent bone resorption. In addition, bisphosphonates induce osteoclast apoptosis (Li, et al., 2011).

The rationale for using drugs such as bisphosphonates in patients with metastatic cancer is that osteoclasts, as the mediators of bone absorption, are often activated by the tumors and thus allow metastatic invasion into the medulla of the vertebrae. Preventing such activity may reduce metastatic invasion and spread (Orita, et al., 2011). In addition, by inhibiting bone resorption, a secondary correction of hypercalcaemia and hypercalciuria will be achieved (Woodward & Coleman, 2010).

Most importantly, the use of bisphosphonates reduces pain and the occurrence of fracture, as well as the development of new osteolytic lesions and, as a consequence, improves patients' quality of life (Fleisch, 1991). Compounds that are commercially available for use in tumor-induced bone disease are, in order of increasing potency, etidronate, clodronate, pamidronate, and alendronate.

Van Holten-Verzantvoort et al found a significant reduction in morbidity from bone metastases in pamidronate-treated breast cancer patients, with a 30–50% reduction of pain and lower rate of new pathological fractures (van Holten-Verzantvoort, et al., 1991). Thurlimann et al showed that pain relief was achieved in about 30% of patients who received pamidronate every 4 weeks (Thurlimann, et al., 1994).

Side effects from bisphosphonates, including transient low grade fever, nausea, myalgia, gastrointestinal side-effects, bone pain, and mild infusion-site reactions, are usually minimal. More rarely, osteonecrosis of the jaw and long bone "frozen bone" fractures due to long term use have been reported (Kim, et al., 2011; Mercadante, 1997).