An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. Efficacy, tolerability and safety of cannabis‐based medicines for chronic pain management – An overview of systematic reviews Opioids for chronic non-cancer pain Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). Long-term opioid use in non-cancer pain. Cannabinoids in the management of difficult to treat pain Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain Using m-health tools to reduce the misuse of opioid pain relievers Addictive behaviors related to opioid use for chronic pain: A population-based study Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Opioids Compared With Placebo or Other Treatments for Chronic Low Back Pain: An Update of the Cochrane Review Evidence for and against the use of opioid analgesics for chronic nonmalignant low back pain: a review. Transcutaneous electrical nerve stimulation (TENS) for chronic pain - an overview of Cochrane Reviews. Predictors of opioid misuse in patients with chronic pain: a prospective cohort study Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety? Opioid prescribing in the UK: can we avert a public health disaster? Effectiveness of manual therapies: the UK evidence report Randomised trial of oral morphine for chronic non-cancer pain Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: Results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain Clinical Implications of Tapering Chronic Opioids in a Veteran Population. Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. Diagnosis and Treatment of Low Back Pain: A Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society Who benefits from additional drug counseling among prescription opioid-dependent patients receiving buprenorphine-naloxone and standard medical management? Chronic pain in Canada--prevalence, treatment, impact and the role of opioid analgesia. Critical issues on opioids in chronic non-cancer pain:: An epidemiological study [Psychological mechanisms in the transition from acute to chronic pain: over- or underrated?]. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. Pharmacovigilance in hospice/palliative care: net effect of gabapentin for neuropathic pain Local tolerability and effectiveness of Ketospray® 10% cutaneous spray solution. Efficacy and safety of transdermal buprenorphine in the management of children with cancer-related pain.
CONTEXT Chronic pain in patients with advanced cancer poses a serious clinical challenge . The Δ9-tetrahydrocannabinol (THC)/cannabidiol ( CBD ) oromucosal spray ( U.S. Adopted Name , nabiximols ; Sativex ( ® ) ) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group . OBJECTIVES This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer . METHODS In total , 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing , who had participated in a previous three-arm ( THC/CBD spray , THC spray , or placebo ) , two-week parent r and omized controlled trial , entered this open-label , multicenter , follow-up study . Patients self-titrated THC/CBD spray ( n=39 ) or THC spray ( n=4 ) to symptom relief or maximum dose and were regularly review ed for safety , tolerability , and evidence of clinical benefit . RESULTS The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for " pain severity " and " worst pain " domains showed a decrease ( i.e. , improvement ) at each visit in the THC/CBD spray patients . Similarly , the European Organization for Research and Treatment of Cancer Quality of Life Question naire-C30 scores showed a decrease ( i.e. , improvement ) from baseline in the domains of insomnia , pain , and fatigue . No new safety concerns associated with the extended use of THC/CBD spray arose from this study . CONCLUSION This study showed that the long-term use of THC/CBD spray was generally well tolerated , with no evidence of a loss of effect for the relief of cancer-related pain with long-term use . Furthermore , patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time , suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit Medicinal cannabis has already entered mainstream medicine in some countries . This systematic review ( SR ) aim ed at evaluating the efficacy , acceptability and safety of cannabis-based medicines for chronic pain management . Qualitative systematic review of SRs of r and omized controlled trials with cannabis-based medicines for chronic pain management . The Cochrane data bases of SRs , Data base of Abstract s of Review s of Effects and PubMed were search ed for SR published in the period January 2009 to January 2017 . Assessment of the method ological quality of SR was performed by the AMSTAR checklist . Out of 748 papers identified , 10 SRs met the inclusion criteria . The method ological quality was high in four and moderate in six SRs . There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis . There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases ( three SRs ) and in cancer pain ( two SRs ) . Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions . It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the st and ard of 21st century clinical care . SIGNIFICANCE We provide an overview of systematic review s on the efficacy , tolerability and safety of cannabis-based medicines for chronic pain management . There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis . There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain A 36 year old carpenter has a six month history of lower back pain with no specific clinical or radiological findings . As his pain has not responded to paracetamol and non-steroidal anti-inflammatory drugs ( NSAIDs ) , he asks his doctor if he can have “ stronger painkillers ” such as morphine . Opioids are a group of compounds that act by binding to opioid receptors ( μ , κ , and δ ) , which are widely distributed in the brain , spinal cord , and peripheral tissues . They are the mainstay in the management of cancer pain , but published data show a continual increase in the volume of prescribed opioids to manage moderate to severe , chronic , non-cancer pain.1 2 Changes in attitude and aggressive marketing have driven a dramatic increase in use , with more adverse events , including deaths from overdose ( now the second leading cause of accidental death in the US).3 Proponents cl aim that opioids are underused for chronic pain,4 but lack of good scientific data has prevented the formulation of evidence based guidelines for their use , especially in primary care . Several meta-analyses of the effectiveness of opioids have been published . Most of the r and omised clinical trials summarised in these meta-analyses were funded by the pharmaceutical industry and report heterogeneous , short term outcomes in highly selected patients . Non-r and omised and uncontrolled observational studies make up the rest of the literature . Nevertheless , most studies have consistently shown some effectiveness in chronic non-cancer pain by reducing pain intensity . In particular , meta-analyses show the efficacy of opioids in neuropathic pain,5 6 7 although most guidelines regard opioids only as second or third line treatment for such pain because of their risk : benefit profile.8 9 The data are even less encouraging for chronic non-neuropathic pain , the focus of this paper . A 2009 Cochrane review of 10 r and omised or quasi-r and omised controlled trials compared UNLABELLED Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain . The safety of cannabis use for medical purpose s has not been systematic ally evaluated . We conducted a prospect i ve cohort study to describe safety issues among individuals with chronic non-cancer pain . A st and ardized herbal cannabis product ( 12.5 % tetrahydrocannabinol ) was dispensed to eligible individuals for a 1-year period ; controls were individuals with chronic pain from the same clinics who were not cannabis users . The primary outcome consisted of serious adverse events and non-serious adverse events . Secondary safety outcomes included pulmonary and neurocognitive function and st and ard hematology , biochemistry , renal , liver , and endocrine function . Secondary efficacy parameters included pain and other symptoms , mood , and quality of life .  Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group ( 141 current users and 58 ex-users ) and 216 controls ( chronic pain but no current cannabis use ) from 7 clinics across Canada . The median daily cannabis dose was 2.5 g/d . There was no difference in risk of serious adverse events ( adjusted incidence rate ratio = 1.08 , 95 % confidence interval = .57 - 2.04 ) between groups . Medical cannabis users were at increased risk of non-serious adverse events ( adjusted incidence rate ratio = 1.73 , 95 % confidence interval = 1.41 - 2.13 ) ; most were mild to moderate . There were no differences in secondary safety assessment s. Quality -controlled herbal cannabis , when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year , appears to have a reasonable safety profile . Longer-term monitoring for functional outcomes is needed . STUDY REGISTRATION The study was registered with www.controlled-trials.com ( IS RCT N19449752 ) . PERSPECTIVE This study evaluated the safety of cannabis use by patients with chronic pain over 1 year . The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day BACKGROUND The long-term use of opioid analgesic drugs to treat chronic non-cancer pain ( CNCP ) is a major component of pain pharmacotherapy . The interpretation of the evidence concerning its efficacy and risks is currently debated . METHODS An interdisciplinary evidence - and consensus-based S3 guideline was up date d on the basis of a systematic literature search ( CENTRAL , Medline , and Scopus data bases , from October 2008 to October 2013 ) ; meta-analyses of r and omized controlled trials ( ≥ 4 weeks ) ; and a consensus procedure , as specified by the AWMF regulations , including 22 medical and psychological societies and 2 patient self-help organizations . RESULTS 119 publications were used to up date the guideline , and 6 systematic review s with meta-analyses were performed . A nominal group process was used to formulate recommendations concerning the indications and contraindications for the treatment of CNCP with opioid analgesics and the manner in which such treatments should be carried out . Opioid analgesics are an option for the short-term treatment ( 4 - 12 weeks ) of chronic pain due to osteoarthritis ( pain intensity , st and ardized mean difference [ SMD ] : -0.22 and -0.26 ) , diabetic polyneuropathy ( SMD -0.74 ) , post-herpetic neuralgia ( SMD -0.58 ) , and chronic low back pain ( SMD : -0.29 and -0.74 ) . Long-term opioid treatment ( ≥ 26 weeks ) for these diseases benefits only about 25 % of patients . For other conditions , either short- or long-term treatment with opioid analgesics should be considered an individual therapeutic trial . Opioid treatment for pain is contraindicated by primary headaches and by any functional or mental disorder of which pain is a leading manifestation . CONCLUSION To minimize the risks of opioid analgesic treatment , physicians must be aware of its contraindications and must regularly reassess its efficacy and side effects . Pharmacotherapy should be combined with other types of treatment This article review s recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms , as well as r and omized clinical trials employing cannabinoids in pain treatment .  Tetrahydrocannabinol ( THC , Marinol ® ) and nabilone ( Cesamet ® ) are currently approved in the United States and other countries , but not for pain indications . Other synthetic cannabinoids , such as ajulemic acid , are in development . Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation . Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC ( partial CB1 receptor agonist ) and cannabidiol ( CBD , a non-euphoriant , anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects ) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis , and in 2007 for intractable cancer pain . Numerous r and omized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain , rheumatoid arthritis and cancer pain . An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006 . Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles . Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise ABSTRACT Background : Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades , possibly accounting for the current opioid addiction epidemic . Co-morbid drug use in those prescribed opioid analgesics is common , but there are few data on polysubstance use patterns . Objective : We explored patterns of use of cigarette , alcohol , and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics .  Methods : We conducted a secondary data analysis of screening interviews conducted as part of a parent r and omized trial of financial incentives to improve HIV outcomes among drug users . In a convenience sample of people with HIV and chronic pain , we collected self-report data on demographic characteristics ; pain ; patterns of opioid analgesic use  ( both prescribed and illicit ) ; cigarette , alcohol , and illicit drug use ( including cannabis , heroin , and cocaine ) within the past 30 days ; and current treatment for drug use and HIV . Results : Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use ( N = 372 , 47.1 % ) . Illicit drug use was common ( N = 505 , 63.9 % ) , and cannabis was the most commonly used illicit substance ( N = 311 , 39.4 % ) . In multivariate analyses , only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use ( adjusted odds ratio = 0.57 ; 95 % confidence interval : 0.38–0.87 ) . Conclusions / Importance : Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management , which could help to address adverse events associated with opioid analgesic use Background Emergency department ( ED ) patients are among the many groups at risk for prescription drug overdose . There is limited research on how best to communicate with ED patients about options for pain management and the risks of opioids . The aim of this study is to pilot test a web-based , patient-centred educational programme that encourages the patient to have an informed discussion about pain medication options with their ED provider . Methods This multisite , r and omised trial will evaluate an  m-health programme design ed to aid the patient in making an informed decision about their pain treatment . Patients reporting to the ED with an injury-related or pain- related chief complaint who agree to participate are r and omised to receive the  intervention programme , My Healthy Choices , or an attention-matched control . My Healthy Choices pairs tailored education with a patient decision aid to describe what opioid and non-opioid pain medications are , assess the patient 's risk factors for opioid-related adverse effects , and produce a tailored report that patients are encouraged to share with their doctor . Data are collected through surveys at three time points during the ED encounter ( baseline , immediately after the intervention and just before discharge ) , and at a 6-week follow-up survey . The primary outcomes are whether the patient prefers an opioid pain reliever ( OPR ) and whether the patient takes an OPR . Discussion We hope this programme will facilitate patient-provider communication , as well as reduce the number of prescriptions written for OPRs and thus the number of patients exposed to prescription opioids and the associated risks of addiction and overdose . Trial registration number NCT03012087 ; Pre- results Summary An intricate relationship between chronic pain , opioid use and addictive behaviors was demonstrated , and certain addictive behaviors seem to predict or be associated with opioid use in chronic non‐cancer pain . Abstract The growing body of research showing increased opioid use in patients with chronic pain coupled with concerns regarding addiction encouraged the development of this population ‐based study . The goal of the study was to investigate the co‐occurrence of indicators of addictive behaviors in patients with chronic non‐cancer pain in long‐term opioid treatment . The study combined data from the  individual‐based Danish Health Survey in 2010 and the official Danish health and socio‐economic , individual‐based registers . From a simple r and om sample of 25,000 adults ( 16 years or older ) living in Denmark , 13,281 individuals were analyzed through multiple logistic regression analyses to assess the association between chronic pain ( lasting ≥6 months ) , opioid use , health behavior , and body mass index . Six potential addictive behaviors were identified : daily smoking ; high alcohol intake ; illicit drug use in the past year ; obesity ; long‐term use of benzodiazepines ; and long‐term use of benzodiazepine‐related drugs . At least 2 of the 6 addictive behaviors were observed in 22.6 % of the long‐term opioid users with chronic pain compared with 11.5 % of the non‐opioid users with chronic pain and 8.9 % of the individuals without chronic pain . Thus , a strong association was demonstrated between long‐term opioid use and the clustering of addictive behaviors . An intricate relationship between chronic pain , opioid use , and addictive behaviors was observed in this study , which deserves both clinical attention and further research Neuropathic pain ( NeP ) , generated by disorders of the peripheral and central nervous system , can be particularly severe and disabling . Prevalence estimates indicate that 2 % to 3 % of the population in the developed world suffer from NeP , which suggests that up to one million Canadians have this disabling condition . Evidence -based guidelines for the pharmacological management of NeP are therefore urgently needed . R and omized , controlled trials , systematic review s and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting . Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one method ologically sound , r and omized , controlled trial showing significant benefit relative to placebo or another relevant control group . Recommendations for treatment are based on degree of evidence of analgesic efficacy , safety , ease of use and cost-effectiveness .  Analgesic agents recommended for first-line treatments are certain antidepressants ( tricyclics ) and anticonvulsants ( gabapentin and pregabalin ) . Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine . Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain . Recommended fourth-line treatments include cannabinoids , methadone and anticonvulsants with lesser evidence of efficacy , such as lamotrigine , topiramate and valproic acid . Treatment must be individualized for each patient based on efficacy , side-effect profile and drug accessibility , including cost . Further studies are required to examine head-to-head comparisons among analgesics , combinations of analgesics , long-term outcomes , and treatment of pediatric and central Study Design . Systematic review and meta- analysis . Objective . To assess the efficacy of opioids in adults with chronic low back pain ( CLBP ) . Summary of Background Data . Opioids for CLBP has increased dramatically . However , the benefits and risks remain unclear . Methods . We up date d a 2007 Cochrane Review through October 2012 of r and omized controlled trials from multiple data bases . Use of noninjectable opioids in CLBP for at least 4 weeks was compared with placebo or other treatments ; comparisons with different opioids were excluded . Outcomes included pain and function using st and ardized mean difference ( SMD ) or risk ratios with 95 % confidence intervals ( CIs ) , and absolute risk difference with 95 % CI for adverse effects . Study quality was evaluated using Grading of Recommendations Assessment , Development , and Evaluation criteria . Results . Fifteen trials ( 5540 participants ) , including twelve new , met the criteria . Tramadol was better than placebo for pain ( SMD , −0.55 ; 95 % CI , −0.66 to −0.44 ) and function ( SMD , −0.18 ; 95 % CI , −0.29 to −0.07 ) . Compared with placebo , transdermal buprenorphine  decreased pain ( SMD , −2.47 ; 95 % CI , −2.69 to −2.25 ) , but not function ( SMD , −0.14 ; 95 % CI , −0.53 to 0.25 ) . Strong opioids ( morphine , hydromorphone , oxycodone , oxymorphone , and tapentadol ) , were better than placebo for pain ( SMD , −0.43 ; 95 % CI , −0.52 to −0.33 ) and function ( SMD , −0.26 ; 95 % CI , −0.37 to −0.15 ) . One trial demonstrated little difference with tramadol compared with  celecoxib for pain relief .  Two trials ( 272 participants ) found no difference between opioids and antidepressants for pain or function . Review ed trials had low to moderate quality , high drop-out rates , short duration , and limited interpretability of functional improvement . No serious adverse effects , risks ( addiction or overdose ) , or complications ( sleep apnea , opioid-induced hyperalgesia , hypogonadism ) were reported . Conclusion . There is evidence of short-term efficacy ( moderate for pain and small for function ) of opioids to treat CLBP compared with placebo . The effectiveness and safety of long-term opioid therapy for treatment of CLBP remains unproven . Level of Evidence : INTRODUCTION Opioid analgesics are very effective for treating pain , but their chronic use in nonmalignant conditions is controversial . Low back pain is a common condition , and chronic low back pain ( CLBP ) is the most frequent regional pain syndrome in the United States . This article review s the evidence for and against the use of chronic opioid analgesic therapy ( COAT ) for patients with CLBP unrelated to cancer . METHODS A literature review was conducted looking for reports of oral or transdermal opioid analgesic therapy for CLBP . RESULTS There are very few r and omized controlled trials of COAT for CLBP . The scant evidence that is available suggests that over the short-term , COAT is helpful with patients with CLBP . In the published reports , most of which are brief in duration , COAT is associated with moderate side effects but a low risk of abuse or drug addiction .  COAT was not associated with adverse long-term sequelae . Longer-acting opioid analgesics may be preferable to shorter-acting agents . Patient selection and close follow-up are critical to good outcomes . CONCLUSIONS There is a place for the use of chronic oral or transdermal opioid analgesics in the treatment of some patients with CLBP BACKGROUND Chronic pain , considered to be pain lasting more than three months , is a common and often difficult to treat condition that can significantly impact upon function and quality of life . Treatment typically includes pharmacological and non-pharmacological approaches . Transcutaneous electrical nerve stimulation ( TENS ) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain . OBJECTIVES To provide an overview of evidence from Cochrane Review s of the effectiveness of TENS to reduce pain in adults with chronic pain ( excluding headache or migraine).To provide an overview of evidence from Cochrane Review s of the safety of TENS when used to reduce pain in adults with chronic pain ( excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain ( excluding headache or migraine ) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting . To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain ( excluding headache or migraine ) with a view to recommending strategies to reduce any uncertainty . METHODS Search methods We search ed the Cochrane Data base of Systematic Review s ( CDSR ) , in the Cochrane Library , across all years up to Issue 11 of 12 , 2018 . Selection of review sTwo authors independently screened the results of the electronic search by title and abstract against inclusion /exclusion criteria . We included all Cochrane Review s of r and omised controlled trials ( RCTs ) assessing the effectiveness of TENS in people with chronic pain . We included review s if they investigated the following : TENS versus sham ; TENS versus usual care or no treatment/waiting list control ; TENS plus active intervention versus active intervention alone ; comparisons between different types of TENS ; or TENS delivered using different stimulation parameters . Data extraction and analysis Two authors independently extracted relevant data , assessed review quality using the AMSTAR checklist and applied GRADE judgements where required to individual review s. Our primary outcomes included pain intensity and nature/incidence of adverse effects ; our secondary outcomes included disability , health-related quality of life , analgesic medication use and participant global impression of change . MAIN RESULTS We included nine review s investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain . One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies . We therefore extracted data from eight review s which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies .The included review s followed consistent methods and achieved overall high scores on the AMSTAR checklist . The evidence reported within each review was consistently rated as very low quality . Using review authors ' assessment of risk of bias , there were significant method ological limitations in included studies ; and for all review s , sample sizes were consistently small ( the majority of studies included fewer than 50 participants per group).Six of the eight review s presented a narrative synthesis of included studies . Two review s reported a pooled analysis . Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale ( MD -1.58 , 95 % CI -2.08 to -1.09 , P < 0.001 , I² = 29 % , P = 0.22 , 5 studies , 207 participants ) . However the quality of the evidence was very low due to significant method ological limitations and imprecision . A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention ( SMD -0.85 , 95 % CI -1.36 to -0.34 , P = 0.001 , I² = 83 % , P < 0.001 ) . This pooled analysis was judged as offering very low quality evidence due to significant method ological limitations , large between-trial heterogeneity and imprecision . We considered the approach of combining sham and no intervention data to be problematic since we would predict these different comparisons may be estimating different true effects . All remaining review s also reported pain intensity as an outcome measure ; however the data were presented in narrative review form only . Due to method ological limitation and lack of useable data , we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects , nor for the remaining secondary outcomes : disability , health-related quality of life , analgesic medication use and participant global impression of change for any comparisons . We found the included review s had a number of inconsistencies when evaluating the evidence from TENS studies . Approaches to assessing risk of bias around the participant , personnel and outcome -assessor blinding were perhaps the most obvious area of difference across included review s. We also found wide variability in terms of primary and secondary outcome measures , and inclusion /exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions . AUTHORS ' CONCLUSIONS We found the method ological quality of the review s was good , but quality of the evidence within them was very low . We were therefore unable to conclude with any confidence that , in people with chronic pain , TENS is harmful , or beneficial for pain control , disability , health-related quality of life , use of pain relieving medicines , or global impression of change . We make recommendations with respect to future TENS study design s which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic pain Background Opioid misuse can complicate chronic pain management , and the non-medical use of opioids is a growing public health problem . The incidence and risk factors for opioid misuse in patients with chronic pain , however , have not been well characterized . We conducted a prospect i ve cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice . Methods One-hundred and ninety-six opioid-treated patients with chronic , non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals . Opioid misuse was defined as : 1 . Negative urine toxicological screen ( UTS ) for prescribed opioids ; 2 . UTS positive for opioids or controlled substances not prescribed by our practice ; 3 . Evidence of procurement of opioids from multiple providers ; 4 . Diversion of opioids ; 5 . Prescription forgery ; or 6 . Stimulants ( cocaine or amphetamines ) on UTS . Results The mean patient age was 52 years , 55 % were male , and 75 % were white . Sixty-two of 196 ( 32 % ) patients committed opioid misuse . Detection of cocaine or amphetamines on UTS was the most common form of misuse ( 40.3 % of misusers ) . In bivariate analysis , misusers were more likely than non-misusers to be younger ( 48 years vs 54 years , p < 0.001 ) , male ( 59.6 % vs. 38 % ; p = 0.023 ) , have past alcohol abuse ( 44 % vs 23 % ; p = 0.004 ) , past cocaine abuse ( 68 % vs 21 % ; p < 0.001 ) , or have a previous drug or DUI conviction ( 40 % vs 11 % ; p < 0.001 % ) . In multivariate analyses , age , past cocaine abuse ( OR , 4.3 ) , drug or DUI conviction ( OR , 2.6 ) , and a past alcohol abuse ( OR , 2.6 ) persisted as predictors of misuse . Race , income , education , depression score , disability score , pain score , and literacy were not associated with misuse . No relationship between pain scores and misuse emerged . Conclusion Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice . Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed . Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion Inappropriate therapy of postoperative pain in laparoscopic cholecystectomy may lead to late mobilization , patient dissatisfaction , delayed hospital discharge , and chronic pain development . Our objective was to identify the best therapeutic strategy available to the anesthesiologist for the acute postoperative pain of patients su bmi tted to elective laparoscopic cholecystectomy . This is a systematic review that included 36 complete articles indexed in the Medline , Scopus , Web of Science and LILACS data bases , with a five-year time cut ( 2012 to 2016 ) , result ing from controlled and r and omized studies that were su bmi tted to qualitative analysis . In a proposal for multimodal analgesia , it is important to consider the contraindications , adverse effects , dose and optimal timing of interventions . Non-opioid drugs , such as non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase-2 ( COX-2 ) inhibitors , gabapentin/pregabalin , N-methyl-D-aspartate ( NMDA ) receptor antagonists , and others . Opioids may be used at low doses associated with multimodal therapy or are restricted to cases where non-opioid multimodal analgesia is insufficient . We conclude that there is no consensus as to the best analgesic strategy to be implemented in the acute postoperative pain of laparoscopic cholecystectomy , which requires its applicability in an individualized way , based on the scientific evidence found in the literature . As contribution to medical learning and practice , we point out the theoretical enrichment of the analgesic drug options available for the therapy of postoperative pain in patients su bmi tted to elective laparoscopic cholecystectomy , and alert the team to consider the adverse effects of the interventions implemented Background For the past 30 years , opioids have been used to treat chronic nonmalignant pain . This study tests the following hypotheses : ( 1 ) there is no strong evidence -based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective ; and ( 2 ) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected . Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess ( 1 ) the quality of presented evidence ( type of study ) ; and ( 2 ) the duration of the treatment phase . The sufficiency of representation of addiction was assessed by counting the number of articles that represent ( 1 ) editorials ; ( 2 ) articles in the top specialty journals ; and ( 3 ) articles with titles clearly indicating that the addiction-related safety is involved ( topic-in-title articles ) . Results Not a single r and omized controlled trial with opioid treatment lasting > 3 months was found . All studies with a duration of opioid treatment ≥6 months ( n = 16 ) were conducted without a proper control group . Such studies can not provide the consistent good- quality evidence necessary for a strong clinical recommendation . There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general . An inadequate number of chronic pain-related publications were observed with all three types of counted articles : editorials , articles in the top specialty journals , and topic-in-title articles . Conclusion There is no strong evidence -based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective . The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present For many of us working in the field of pain medicine , 2003 represented a turning point . For a decade a more liberal approach to opioid prescribing , supported in part by a steady stream of short-term , r and omised controlled trials and facilitated by a tide of educational initiatives sponsored by pharmaceutical companies selling the next best thing , had put pain specialists ahead of the pack . We thought we had at our fingertips the newly acquired knowledge to open the floodgates and deploy our most potent weapon , strong opioids , in the battle to manage persistent pain . But then a distant warning bell was heard . Jane Ballantyne and Jianren Mao published a paper in the New Engl and Journal of Medicine in which they sounded a number of caution ary notes.1 They pointed out that opioids are not all good news when used in the long term and , in particular , the way that opioids are used in clinical practice can not be justified from the information we derive from clinical trials . A year later there were more loud noises off . An editorial in Pain described a developing epidemic of opioid misuse in parallel with the marked and progressive rise in opioid prescribing.2 The debate shifted from ‘ Why not prescribe opioids ? ’ to ‘ Why not to prescribe opioids ? ’ Data from the USA are unambiguous . The increase in prescription of opioids for pain has been accompanied by an increase in prescription drug misuse and additional risk of morbidity and mortality.3–10 The prescribing statistics from other developed countries , including the UK , show a similar rate of rise in opioid use , so it is no surprise to read dire warnings of the storm of misuse and opioid-related deaths that is about to hit us.11–13 It is also unsurprising that the mix of a good story about the man in the street becoming addicted and a dig at doctors has made its way into our daily newspapers.14–16 For certain , every patient who becomes an addict as a result of irresponsible prescribing or marketing is a patient too many . Addiction destroys the lives of sufferers and their families and is a barrier to successful pain management . Support groups representing patients who have run into trouble with opioids and other drugs have recently found a voice in the UK , and this has led to both a parliamentary inquiry and a coordinated Department of Health work stream to address the problem.17,18 As part of this work stream , the situation with regard to addiction and mortality in the UK is becoming clearer . There may be limitations in the way that data regarding addiction to prescribed and over-the-counter ( OTC ) drugs are collected and it is likely that addiction to medicinal opioids is somewhat under-reported . The National Drug Treatment Monitoring System data show that addiction to prescribed and OTC opioids does occur but the numbers of patients presenting for support in relation to addiction to prescribed opioids has remained stable over a 5-year period.18 The Office for National Statistics records data on all drug-related deaths . A review of the 2010 data show unchanged or falling death rates in relation to co-codamol , co-dydramol and dihydrocodeine ; a steady increase in deaths from tramadol since 2003 ( 87 tramadol-related deaths in 2009 and 132 deaths in 2010 ) ; and a rise in codeine-related deaths from 2006 to 2009 , which now seems to have stabilised.19 So what does all this mean ? As far as we know , we do not , in the UK , have an epidemic of addiction and opioid-related mortality as a result of increased opioid prescribing – or at least not yet . We have only really just started looking properly . We might speculate that the inability of pharmaceutical companies to market opioids directly to patients , the current primary care set-up in which most patients still have a family doctor who has a pretty good grip on who , apart from themselves , is giving what to patients , and a culture in which patients , on the whole , believe that doctors know best , might act as brakes on the addiction and mortality juggernaut . However , this is no time for complacency . What the addiction and mortality data do not tell us is the enormous clinical challenge and healthcare burden in relation to patients with persistent pain on unhelpful and very-high-dose opioids who , in some cases for years , are burdened by all the harms and none of the benefits of opioid treatment . We do not know what the scale of the opioid-related harms is , but all of us see patients in this trap in almost every clinic . We must remain vigilant and diligent in our efforts to improve what we know about safe prescribing of opioids and opioid-related harms . Caution ary guidance exists , but given the lack of a large enough data set to give us the answers we so badly need in relation to long-term opioid therapy , such guidance is still heavily weighted by professional opinion . It may be that we have a real opportunity here in the UK to somehow head off the impending storm by getting the message about safe prescribing to everyone who needs to know it , and to support the victims who have been already hit by the opioid problem with improved recognition and management of opioid burdens . If we could get it right it would be a public health triumph . If we do not , and the UK ends up in the undoubted opioid chaos seen in the USA , it will be as bad for those who do not need opioids as for those who do Background The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions . Methods The conclusions are based on the results of systematic review s of r and omized clinical trials ( RCTs ) , widely accepted and primarily UK and United States evidence -based clinical guidelines , plus the results of all RCTs not yet included in the first three categories . The strength/ quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs . Results By September 2009 , 26 categories of conditions were located containing RCT evidence for the use of manual therapy :  13 musculoskeletal conditions , four types of chronic headache and nine non-musculoskeletal conditions . We identified 49 recent relevant systematic review s and 16 evidence -based clinical guidelines plus an additional 46 RCTs not yet included in systematic review s and guidelines .Additionally , brief references are made to other effective non-pharmacological , non-invasive physical treatments . Conclusions Spinal manipulation/mobilization is effective in adults for : acute , subacute , and chronic low back pain ; migraine and cervicogenic headache ; cervicogenic dizziness ;  manipulation/mobilization is effective for several extremity joint conditions ; and thoracic manipulation/mobilization is effective for acute/subacute neck pain . The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration , and for manipulation/mobilization for mid back pain , sciatica , tension-type headache , coccydynia , temporom and ibular joint disorders , fibromyalgia , premenstrual syndrome , and pneumonia in older adults . Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation , or for Stage 1 hypertension when added to an antihypertensive diet . In children , the evidence is inconclusive regarding the effectiveness for otitis media and enuresis , and it is not effective for infantile colic and asthma when compared to sham manipulation . Massage is effective in adults for  chronic low back pain and chronic neck pain . The evidence is inconclusive for knee osteoarthritis , fibromyalgia , myofascial pain syndrome , migraine headache , and premenstrual syndrome . In children , the evidence is inconclusive for asthma and infantile colic BACKGROUND The use of opioid analgesics for chronic non-cancer pain is controversial . Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction . METHODS We undertook a r and omised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine , anti-inflammatory agents , and antidepressants .  Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine ( active placebo ) in doses up to 1 mg twice daily over three-week titration , six-week evaluation , and two-week washout phases . Pain intensity , pain relief , and drug liking were rated weekly and psychological features , functional status , and cognition were assessed at baseline and at the end of each evaluation phase . FINDINGS After dose titration in the 46 patients who completed the study , the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg . On visual analogue scales , the morphine group showed a reduction in pain intensity relative to placebo in period I ( p = 0.01 ) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline ( p = 0.02 ) . No other significant differences were detected . INTERPRETATION In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin , nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement & NA ; Our objective was to investigate the efficacy and safety of alvimopan , a peripherally acting mu‐opioid receptor ( PAM‐OR ) antagonist , in subjects with non‐cancer pain and opioid‐induced bowel dysfunction ( OBD ) , and to identify at least one treatment regimen that improves OBD . Following a 2‐week baseline period , 522 subjects reporting <3 spontaneous bowel movements (SBMs)/week ( with ⩾25 % accompanied by a sensation of incomplete evacuation , straining , or lumpy hard stools ) , requiring analgesia equivalent to ⩾30 mg oral morphine/day were r and omized  to alvimopan 0.5 mg twice daily ( BID ) , 1 mg once daily ( QD ) , 1 mg BID , or placebo for 6 weeks . Compared with placebo , there was a statistically and clinical ly significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment ( primary endpoint ) with alvimopan 0.5 mg BID ( + 1.71 mean SBMs/week ) , alvimopan 1 mg QD ( + 1.64 ) and alvimopan 1 mg BID ( + 2.52 ) ; P < 0.001 for all comparisons . Increased SBM frequency and additional treatment effects , including improvements in symptoms such as straining , stool consistency , incomplete evacuation , abdominal bloating/discomfort , and decreased appetite , were sustained over 6 weeks . The most frequently reported adverse events were abdominal pain , nausea , and diarrhea , occurring more frequently in the higher dosage groups . The alvimopan 0.5 mg BID regimen demonstrated the best benefit‐to‐risk profile for managing OBD with alvimopan in this study population , with a side effect profile similar to that of placebo . There was no evidence of opioid analgesia antagonism . Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia OBJECTIVE To determine if patients receiving chronic opioid therapy  can be tapered to lower opioid doses without a subsequent increase in pain . DESIGN Retrospective and prospect i ve chart review at a VA Medical Center . METHODS Patients were included in the review if they were prescribed opioids chronically for at least 90 consecutive days and if a plan to taper opioid doses was agreed upon . Patients 89 years of age and older , patients with cancer , and patients exhibiting aberrant behavior were excluded . The primary endpoint was to determine the percent reduction of morphine equivalents ( ME ) over a 12-month period . Secondary endpoints included percent reduction of ME at 3 and 6 months , change in pain perception at 3 , 6 , and 12 months , and change in the number of adjuvant medications prescribed at 3 , 6 , and 12 months . Data were analyzed utilizing descriptive statistics . RESULTS A total of 50 patient charts were included in the study . The average percent reduction of opioid doses was 46 % over a 12-month period . Seventy percent of patients either experienced no change in pain or had less pain when comparing baseline to 12 months . An equal percentage of patients either had no change in the number of adjuvant medications prescribed or had more adjuvant medications prescribed when comparing baseline to 12 months . CONCLUSIONS Patients in the population studied can be successfully tapered to lower opioid doses and may not necessarily experience more pain PURPOSE The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine . PATIENTS AND METHODS A prospect i ve r and omized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management . Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need . Opioid  doses , adjuvant medications , symptoms associated with opioid therapy , pain intensity , and pain mechanisms were recorded . The opioid escalation indices in percentage ( OEI% ) and milligrams ( OEImg ) were calculated . The effective analgesic score ( EAS ) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals . RESULTS differences in pain intensity were found . Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine . Seven patients in the methadone group maintained the same initial dosage until death , whereas only one patient in the morphine group did not require opioid dose escalation . A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported . Symptom frequencies and intensities were similar in the two groups . CONCLUSION Methadone is a drug of indisputable value in the treatment of cancer pain , and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain Low back pain is the fifth most common reason for all physician visits in the United States ( 1 , 2 ) . Approximately one quarter of U.S. adults reported having low back pain lasting at least 1 whole day in the past 3 months ( 2 ) , and 7.6 % reported at least 1 episode of severe acute low back pain ( see Glossary ) within a 1-year period ( 3 ) . Low back pain is also very costly : Total incremental direct health care costs attributable to low back pain in the U.S. were estimated at $ 26.3 billion in 1998 ( 4 ) . In addition , indirect costs related to days lost from work are substantial , with approximately 2 % of the U.S. work force compensated for back injuries each year ( 5 ) . Many patients have self-limited episodes of acute low back pain and do not seek medical care ( 3 ) . Among those who do seek medical care , pain , disability , and return to work typically improve rapidly in the first month ( 6 ) . However , up to one third of patients report persistent back pain of at least moderate intensity 1 year after an acute episode , and 1 in 5 report substantial limitations in activity ( 7 ) . Approximately 5 % of the people with back pain disability account for 75 % of the costs associated with low back pain ( 8) . Many options are available for evaluation and management of low back pain . However , there has been little consensus , either within or between specialties , on appropriate clinical evaluation ( 9 ) and management ( 10 ) of low back pain . Numerous studies show unexplained , large variations in use of diagnostic tests and treatments ( 11 , 12 ) . Despite wide variations in practice , patients seem to experience broadly similar outcomes , although costs of care can differ substantially among and within specialties ( 13 , 14 ) . The purpose of this guideline is to present the available evidence for evaluation and management of acute and chronic low back pain ( see Glossary ) in primary care setting s. The target audience for this guideline is all clinicians caring for patients with low ( lumbar ) back pain of any duration , either with or without leg pain . The target patient population is adults with acute and chronic low back pain not associated with major trauma . Children or adolescents with low back pain ; pregnant women ; and patients with low back pain from sources outside the back ( nonspinal low back pain ) , fibromyalgia or other myofascial pain syndromes , and thoracic or cervical back pain are not included . These recommendations are based on a systematic evidence review summarized in 2 background papers by Chou and colleagues in this issue ( 15 , 16 ) from an evidence report by the American Pain Society ( 17 ) . The evidence report ( 17 ) discusses the evidence for the evaluation , and the 2 background papers ( 15 , 16 ) summarize the evidence for management . Methods The literature search for this guideline included studies from MEDLINE ( 1966 through November 2006 ) , the Cochrane Data base of Systematic Review s , the Cochrane Central Register of Controlled Trials , and EMBASE . The literature search included all English- language articles reporting on r and omized , controlled trials of nonpregnant adults ( age > 18 years ) with low back pain ( alone or with leg pain ) of any duration that evaluated a target medication and reported at least 1 of the following outcomes : back-specific function , generic health status , pain , work disability , or patient satisfaction .  The American College of Physicians ( ACP ) and the American Pain Society ( APS ) convened a multidisciplinary panel of experts to develop the key questions and scope used to guide the evidence report , review its results , and formulate recommendations . The background papers by Chou and colleagues ( 15 , 16 ) provide details about the methods used for the systematic evidence review . This guideline grade s its recommendations by using the ACP 's clinical practice guidelines grading system , adapted from the classification developed by the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) work group ( Appendix Table 1 ) ( 18 ) . The evidence in this guideline was first evaluated by the ACP/APS panel by using a system adopted from the U.S. Preventive Services Task Force for grading strength of evidence , estimating magnitude of benefits , and assigning summary ratings ( Appendix Tables 2 , 3 , and 4 ) ( 19 ) . The evidence was independently review ed by the ACP 's Clinical Efficacy Assessment Subcommittee . The ratings for individual low back pain interventions discussed in this guideline are summarized in Appendix Table 5 for acute low back pain ( < 4 weeks ' duration ) and in Appendix Table 6 for chronic/subacute low back pain ( > 4 weeks ' duration ) . This guideline considered interventions to have proven benefits only when they were supported by at least fair- quality evidence and were associated with at least moderate benefits ( or small benefits but no significant harms , costs , or burdens ) . Figures 1 and 2 present an accompanying algorithm . Appendix Table 1 . The American College of Physicians Clinical Practice Guidelines Grading System Appendix Table 2 . Methods for Grading the Strength of the Overall Evidence for an Intervention Appendix Table 3 . Definitions for Estimating Magnitude of Effects Appendix Table 4 . Recommendations and Summary Ratings Appendix Table 5 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Acute Low Back Pain Appendix Table 6 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Chronic or Subacute Low Back Pain Figure 1 . Initial evaluation of low back pain ( LBP Figure 2 . Management of low back pain ( LBP Recommendations : Evaluation of Low Back Pain Recommendation 1 : Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy or spinal stenosis , or back pain potentially associated with another specific spinal cause . The history should include assessment of psychosocial risk factors , which predict risk for chronic disabling back pain ( strong recommendation , moderate- quality evidence ) . More than 85 % of patients who present to primary care have low back pain that can not reliably be attributed to a specific disease or spinal abnormality ( nonspecific low back pain [ see Glossary ] ) ( 20 ) . Attempts to identify specific anatomical sources of low back pain in such patients have not been vali date d in rigorous studies , and classification schemes frequently conflict with one another ( 21 ) . Moreover , no evidence suggests that labeling most patients with low back pain by using specific anatomical diagnoses improves outcomes . In a minority of patients presenting for initial evaluation in a primary care setting , low back pain is caused by a specific disorder , such as cancer ( approximately 0.7 % of cases ) , compression fracture ( 4 % ) , or spinal infection ( 0.01 % ) ( 22 ) . Estimates for prevalence of ankylosing spondylitis in primary care patients range from 0.3 % ( 22 ) to 5 % ( 23 ) . Spinal stenosis ( see Glossary ) and symptomatic herniated disc ( see Glossary ) are present in about 3 % and 4 % of patients , respectively . The cauda equina syndrome ( see Glossary ) is most commonly associated with massive midline disc herniation but is rare , with an estimated prevalence of 0.04 % among patients with low back pain ( 24 ) . A practical approach to assessment is to do a focused history and physical examination to determine the likelihood of specific underlying conditions and measure the presence and level of neurologic involvement ( 24 , 25 ) . Such an approach facilitates classification of patients into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy ( see Glossary ) or spinal stenosis ( suggested by the presence of sciatica [ see Glossary ] or pseudoclaudication ) , and back pain potentially associated with another specific spinal cause . The latter category includes the small proportion of patients with serious or progressive neurologic deficits or underlying conditions requiring prompt evaluation ( such as tumor , infection , or the cauda equina syndrome ) , as well as patients with other conditions that may respond to specific treatments ( such as ankylosing spondylitis or vertebral compression fracture ) . Diagnostic triage into 1 of these 3 categories helps guide subsequent decision making . Clinicians should inquire about the location of pain , frequency of symptoms , and duration of pain , as well as any history of previous symptoms , treatment , and response to treatment . The possibility of low back pain due to problems outside the back , such as pancreatitis , nephrolithiasis , or aortic aneurysm , or systemic illnesses , such as endocarditis or viral syndromes , should be considered . All patients should be evaluated for the presence of rapidly progressive or severe neurologic deficits , including motor deficits at more than 1 level , fecal incontinence , and bladder dysfunction . The most frequent finding in the cauda equina syndrome is urinary retention ( 90 % sensitivity ) ( 24 ) . In patients without urinary retention , the probability of the cauda equina syndrome is approximately 1 in 10000 . Clinicians should also ask about risk factors for cancer and infection . In a large , prospect i ve study from a primary care setting , a history of cancer ( positive likelihood ratio , 14.7 ) , unexplained weight loss ( positive likelihood ratio , 2.7 ) , failure to improve after 1 month ( positive likelihood ratio , 3.0 ) , and age older than 50 years ( positive likelihood ratio , 2.7 ) were each associated with a higher likelihood for cancer ( 26 ) . The posttest probability of cancer in patients presenting with back pain increases from approximately 0.7 % to 9 % in patients with a history of cancer ( not including nonmelanoma skin cancer ) . In patients with any 1 of the other 3 risk factors , the likelihood of cancer only increases to approximately 1.2 % ( 26 ) . Features predicting the presence of vertebral infection have not been well studied BACKGROUND In the multi-site Prescription Opioid Addiction Treatment Study ( POATS ) , conducted within the National Drug Abuse Clinical Trials Network , participants r and omly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes . However , research with other substance-dependent population s shows that subgroups of participants may benefit from a treatment although the entire population does not . METHOD We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management , either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence . Problem severity was measured by a history of heroin use , higher Addiction Severity Index drug composite score , and chronic pain . Adequate treatment adherence was defined a priori as attending at least 60 % of all offered sessions . RESULTS Patients who had ever used heroin and received drug counseling  were more likely to be successful ( i.e. , abstinent or nearly abstinent from opioids ) than heroin users who received medical management  alone , but only if they were adherent to treatment and thus received adequate exposure to counseling ( OR=3.7 , 95 % CI=1.1 - 11.8 , p=0.03 ) . The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score . CONCLUSIONS These findings emphasize the importance of treatment adherence , and suggest that patients with prescription opioid dependence are a heterogeneous group , with different optimal treatment strategies for different subgroups OBJECTIVE To assess the prevalence , treatment and impact of chronic pain in Canada . METHODS A stratified r and om sample of 2012 adult Canadians ( weighted by sex , age and region according to 1996 census data ) was surveyed by telephone in 2001 to determine the prevalence of chronic pain , defined as continuous or intermittent pain for at least six months . A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain . RESULTS Chronic noncancer pain was reported by 29 % of the respondents , with increased frequency in women and older age groups . The average duration of pain was 10.7 years and the average intensity was 6.3 ( on a scale from 1 to 10 ) , with 80 % reporting moderate or severe pain . Anti-inflammatory agents were prescribed for 49 % of respondents and opioid analgesics were prescribed for 22 % ( two-thirds of these were codeine ) . Almost 70 % were worried about addiction potential , and one-third felt that strong analgesics should be reserved for terminal illnesses . Almost one-half were unable to attend social and family events , and the mean number of days absent from work in the past year due to chronic pain was 9.3 . INTERPRETATION Chronic noncancer pain is common in Canadian adults and has a major social and economic impact . Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain , less than 10 % of chronic pain patients taking prescription medication were treated with a major opioid . Chronic pain is undertreated in Canada , and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program & NA ; The aim of the study was epidemiologically to evaluate the long‐term effects of opioids on pain relief , quality of life and functional capacity in long‐term/chronic non‐cancer pain . The study was based on data from the 2000 Danish Health and Morbidity Survey . As part of a representative National r and om sample of 16,684 individuals ( > 16 years of age ) , 10,066 took part in an interview and completed a self‐administered question naire . Cancer patients were excluded . The interview and the self‐administered question naire included questions on chronic/long‐lasting pain ( > 6 months ) , health‐related quality of life ( SF‐36 ) , use of the health care system , functional capabilities , satisfaction with medical pain treatment and regular or continuous use of medications .  Participants reporting pain were divided into opioid and non‐opioid users . The analyses were adjusted for age , gender , concomitant use of anxiolytics and antidepressants and pain intensity . Pain relief , quality of life and functional capacity among opioid users were compared with non‐opioid users . Opioid usage was significantly associated with reporting of moderate/severe or very severe pain , poor self‐rated health , not being engaged in employment , higher use of the health care system , and a negative influence on quality of life as registered in all items in SF‐36 . Because of the cross‐sectional nature causative relationships can not be ascertained . However , it is remarkable that opioid treatment of long‐term/chronic non‐cancer pain does not seem to fulfil any of the key outcome opioid treatment goals : pain relief , improved quality of life and improved functional capacity INTRODUCTION During the last 20 years a great number of studies have emphasized the potential role of psychological factors as relevant predictors for the first onset of back pain as well as for the development of chronic pain . The formulation of a biopsychosocial perspective of the etiology and chronicity of back pain was a natural consequence . Actual questions concern the relative impact of psychological risk factors in the process of chronicity of back pain compared to biomedical , social and occupational factors . METHODS Whereas several review articles regarding the role of psychological risk factors are available up to now , a recently published review conducted by Steven Linton was the first systematic analysis of well controlled prospect i ve studies published since 1967 . Using a grading system similar to that recommended for guidelines the author defined a level A evidence when at least two good- quality prospect i ve studies supported the prospect i ve power of a variable . Level B evidence had support from one prospect i ve study . Level C represented inconclusive data and level D indicated that no studies met the criteria . Based on a literature search of more than 900 studies , 37 good- quality prospect i ve studies were analysed in detail . RESULTS The results indicated level A evidence for the following interrelations : ( 1 ) Psychosocial variables , especially chronic distress in daily life , depression and work dissatisfaction were clearly associated with the onset of back and neck pain ( 2 ) . Psychological variables , especially chronic stress in daily life , work dissatisfaction , depression and pain-related cognitions and coping behaviour were clearly linked to the transition from acute to chronic pain and disability ( 3 ) . Psychological variables generally had more prospect i ve power than biomedical , social or objective occupational variables . Among the pain-related cognitions , catastrophizing and fear-avoidance-beliefs yielded the most empirical support . Among coping behaviour passive coping stretegies such as avoiding behaviour was most important . At least level B evidence has been shown for the counterpart of an extreme suppressive coping behaviour . Patients who tended to suppress or ignore pain in order to finish all activities they started , who were unable to integrate phases of passive relaxation into the daily routine displayed a high risk of chronicity of pain 6 months after an acute phase of pain . One international and two German good- quality prospect i ve studies have shown the predictive power of a maladaptive suppressive behaviour pattern . Based on the avoidance-endurance-model of pain chronification , both extreme and one-sided passive pain coping as well as one-sided suppressive coping modes were conceptualized as maladaptive due to the process of chronicity . We assume that extreme passive behaviour will lead to immobility and muscular atrophy . Neurophysiological processes of sensitization will further lead to the development of chronic pain . On the other h and , extreme suppressive behaviour will lead to an overuse of muscles and joints with a repetitive combination of muscular hyperactivity and pain . These repetitive pain experiences will also elicit neurophysiological processes of sensitization . ( 4 ) Psychosocial variables displayed more predictive power than biomedical or biomechanical factors . ( 5 ) Psychosocial factors may be used as predictors of the risk for developing long-term pain and disability . Mixed empirical evidence has been shown for the role of personality factors ( level C evidence ) and no support has been found for the idea of a " pain prone " personality disorder or for the role of sexual and physical abuse . DISCUSSION 20 years of research , several qualitative review s and a recently published systematic review of 37 good- quality prospect i ve studies regarding the role of psychological , biomedical , social and objective occupational factors in the process of chronicity of back pain revealed that psychological factors are significantly related to the onset of back pain as well as to the development of chronic pain . Furthermore , the psychological factors displayed more predictive power than biomedical or biomechanical variables . As a consequence for clinical practice , these psychological risk factors have to be considered as " yellow flags " if a back pain problem wo n't respond to medical treatment for more than four weeks . As a further consequence , special risk factor - based psychosocial interventions should be offered in addition to the medical treatment to patients with high psychological risk factors for the development of chronic pain . The efficacy of such an interdisciplinary care in the very early phases of back pain in order to prevent chronicity of pain and disability has been published recently by our group PURPOSE The anesthetic ketamine is widely used for pain related to cancer , but the evidence to support its use in this setting is weak . This study aim ed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and st and ard adjuvant therapy in the management of chronic uncontrolled cancer pain .  Ketamine would be considered of net benefit if it provided clinical ly relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity . PATIENTS AND METHODS In this multisite , dose-escalation , double-blind , r and omized , placebo-controlled phase III trial , ketamine or placebo was delivered subcutaneously over 3 to 5 days . RESULTS In all , 185 participants were included in the primary analysis . There was no significant difference between the proportion of positive outcomes ( 0.04 ; 95 % CI , -0.10 to 0.18 ; P = .55 ) in the placebo and intervention arms ( response rates , 27 % [ 25 of 92 ] and 31 % [ 29 of 93 ] ) . Pain type ( nociceptive v neuropathic ) was not a predictor of response . There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 ( incidence rate ratio , 1.95 ; 95 % CI , 1.46 to 2.61 ; P < .001 ) and throughout the study . Those receiving ketamine were more likely to experience a more severe grade of adverse event per day ( odds ratio , 1.09 ; 95 % CI , 1.00 to 1.18 ; P = .039 ) . The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 ( 95 % CI , six to ∞ ) . The number needed to harm , because of toxicity-related withdrawal , was six ( 95 % CI , four to 13 ) . CONCLUSION Ketamine does not have net clinical benefit when used as an adjunct to opioids and st and ard coanalgesics in cancer pain Objective Hospice/palliative care patients may differ from better studied population s , and data from other population s can not necessarily be extrapolated into hospice/palliative care clinical practice . Pharmacovigilance studies provide opportunities to underst and the harms and benefits of medications in routine practice . Gabapentin , a γ-amino butyric acid analogue antiepileptic drug , is commonly prescribed for neuropathic pain in hospice/palliative care . Most of the evidence however relates to non-malignant , chronic pain syndromes ( diabetic neuropathy , postherpetic neuralgia , central pain syndromes , fibromyalgia ) . The aim of this study was to quantify the immediate and short-term clinical benefits and harms of gabapentin in routine hospice/palliative care practice . Design Multisite , prospect i ve , consecutive cohort . Population 127 patients , 114 of whom had cancer , who started gabapentin for neuropathic pain as part of routine clinical care . Setting s 42 centres from seven countries . Data were collected at three time points — at baseline , at day 7 ( and at any time ; immediate and short-term harms ) and at day 21 ( clinical benefits ) . Results At day 21 , the average dose of gabapentin for those still using it ( n=68 ) was 653 mg/24 h ( range 0–1800 mg ) and 54 ( 42 % ) reported benefits , of whom 7 ( 6 % ) experienced complete pain resolution . Harms were reported in 39/127 ( 30 % ) patients at day 7 , the most frequent of which were cognitive disturbance , somnolence , nausea and dizziness . Ten patients had their medication ceased due to harms . The presence of significant comorbidities , higher dose and increasing age increased the likelihood of harm . Conclusions Overall , 42 % of people experienced benefit at a level that result ed in continued use at 21 days BACKGROUND Orally administrated nonsteroidal anti-inflammatory drugs are effective in the treatment of a variety of acute and chronic pain conditions but their use may be associated with serious systemic adverse effects which are correlated with the therapeutic plasma levels of the drug . In order to minimize the incidence of drug related systemic events , topical formulations of the nonsteroidal anti-inflammatory drugs have been developed . A recently performed review of the evidence from r and omized , double-blind , placebo controlled trials with topically applied NSAIDs in the treatment of acute pain confirmed the previously described pain relief effectiveness . For all topical nonsteroidal anti-inflammatory drugs combined , in comparison to placebo , the number needed to treat ( NNT ) to achieve a clinical ly meaningful pain relief of 50 % was 4.5 ( 3.9 to 5.3 ) for treatment periods of 6 to 14 days . Local skin reactions were generally mild and transient , and did not differ from placebo . OBJECTIVES The present is an observational , multicenter , open-label , non-interventional , post-authorization safety study as it is defined by Article 21 of the European Clinical Trials Directive 2001/20/EC . The main objective of this study was to evaluate the local tolerability and the therapeutic efficacy of static and pain on movement intensity reduction of Ketospray ® 10 % cutaneous spray solution administered in accordance with the terms of the marketing authorization and last version of summary of product characteristics approved by National Medicines Agency of Romania . METHODS In compliance with the Post-marketing study type , the assignment of the patient to a particular therapeutic strategy fell within current practice . The prescription of the medicine was not subject to compliance with predefined patients ' characteristics . No specific , out of the daily practice routine diagnostic , monitoring , instrumental or laboratory assessment s were foreseen by the study protocol . Patients ' data were collected into respective case report forms . Study medication , Ketoprofen 10 % Cutaneous Spray Solution was administered to the affected area at the dose of 3 - 6 spray puffs , 2 - 3 times a day , for 7 days . According to the study type , descriptive statistical methods were applied . Since almost half of the patients were treated with combination of the pain relieving medications , sizing of the pain relieving effects , as NNT , between the two groups was made . FINDINGS There were 2020 study subjects in safety and ITT analysis population and 1802 ( 89 % ) in PP efficacy analysis population . There were 4 types of injuries : non-complicated strain-sprain ( 555 ) , soft tissue contusion ( 323 ) , low back pain ( 461 ) and osteoarthritis ( 681 patients ) . Ten patients reported 13 side effects of which 10 were recognized by investigators as adverse drug reactions . All side effects were non-serious , listed , application site skin changes . Remarkable reductions of static and pain on movement intensity were experienced by patients irrespective of the type of the injury and the type of the treatment . However , a clinical ly meaningful benefit of the concomitantly prescribed pain relieving medications was not observed for any type of pain . The lowest NNT ( 14 ) was obtained for the reduction of pain at rest in patients with strain-sprain or soft tissue contusions . The highest NNT ( 283 ) was for pain at rest in patients treated for the exacerbation of the chronic pain . CONCLUSIONS The results of the current post-authorization study confirm beneficial pain intensity reducing efficacy of Ketospray 10 % associated with good local tolerability of 7 days treatment course . Concomitant administration of systemic pain relieving medication did not substantially contribute neither to the relief of pain at rest nor of pain on movement among the subjects of respective study population BACKGROUND The current study investigated the efficacy , safety , tolerability , and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population . PROCEDURE Sixteen pediatric patients with moderate to severe cancer-related pain not satisfactorily controlled with previous non-opioid therapies were enrolled .  Transdermal buprenorphine was administered following a 72 hour schedule and rescue medication ( tramadol ) was allowed for breakthrough pain . Pain intensity was assessed using the Wong-Baker faces pain rating scale ( WBS ) and other parameters related to the global quality of life were evaluated . Children 's evaluations of efficacy , compliance , and tolerability were recorded using numerical scales . Adverse events were monitored during the study and the medications needed to control opioid-related nausea and constipation were recorded . RESULTS Eleven patients ( 68.75 % ) responded to transdermal buprenorphine after 2 weeks of treatment . Pain intensity measured with WBS decreased from 6.25 at baseline to 1.38 at Day + 60 ( P < 0.001 ) . All outcome measures of global quality of life ( quality of sleep , alimentation , play and activity , speech , and crying ) significantly improved over the 60-day study period . Children 's evaluations of compliance and tolerability of the drug were always positive over the entire period of treatment . No severe adverse events were recorded . Opioid-related nausea was well controlled with medication on request , and the need for laxative therapy was greater at the end of the second month of treatment . CONCLUSIONS Transdermal buprenorphine was found to represent an efficient , safe and well tolerated approach to the management of children 's chronic cancer pain
There was an increased risk of non-serious AEs with cannabinoids compared with placebo .
Conclusions There was moderate evidence to support cannabinoids in treating chronic , non-cancer pain at 2 weeks .
Similar results were observed at later time points , but the confidence in effect is low .
There is little evidence that cannabinoids increase the risk of experiencing serious AEs , although non-serious AEs may be common in the short-term period following use
Background For patients with chronic , non-cancer pain , traditional pain-relieving medications include opioids , which have shown benefits but are associated with increased risks of addiction and adverse effects .
Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of r and omized clinical trials in recent years ; therefore , a systematic review of the evidence was warranted .
Objective To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic , non-cancer-related pain .