Amitriptyline in the Prophylaxis of Central Poststroke Pain: Preliminary Results of 39 Patients in a Placebo-Controlled, Long-Term Study Repetitive transcranial magnetic stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect on central poststroke pain. Intravenous lidocaine in central pain Chapter 46 Pain following spinal cord injury. Central poststroke pain in young ischemic stroke survivors in the Helsinki Young Stroke Registry Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation Mind-Body Interventions, Psychological Stressors, and Quality of Life in Stroke Survivors: A Systematic Review Lamotrigine for central poststroke pain Cannabinoids in the management of difficult to treat pain Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. Short-term effect of local muscle vibration treatment versus sham therapy on upper limb in chronic post-stroke patients: a randomized controlled trial.
Background and Purpose — We performed a double-blind , placebo-controlled study to investigate the effectiveness of amitriptyline for the prophylactic treatment of patients with acute thalamic stroke in preventing central poststroke pain . Methods — Subject received , in a r and omized sequence , either amitriptyline titrated from 10 to 75 mg in extended-release form or placebo over a therapy period of 365 days . We documented the time when pain developed ; the intensity , type , site , and distribution of pain ; and the presence/absence and type of allodynia . Results — Thirty-nine patients ( 23 women and 16 men ; age range , 36 to 68 years ) with central poststroke pain participated . The placebo group showed a pain rate of 21 % within 1 year after the diagnosis of thalamic stroke compared with 17 % in the group under prophylactic treatment with amitriptyline .  Average ( SE ) time to pain was 318 ( 23 ) days for patients in the placebo group and 324 ( 24 ) days for patients in the amitriptyline group . Conclusions — With the achieved sample sizes of this study and a pain rate of approximately 21 % in the placebo group , any near-perfect pain protection would have been detected . Near-perfect pain protection , in this context , refers to pain in < 2.4 % of the recruited patients treated with amitriptyline or in approximately 89 % of placebo-treated patients . Larger studies are recommended to test the hypothesis that prophylactic amitriptyline reduces but does not completely prevent central poststroke pain UNLABELLED Central poststroke pain ( CPSP ) is caused by an encephalic vascular lesion of the somatosensory pathways and is commonly refractory to current pharmacologic treatments . Repetitive transcranial magnetic stimulation ( rTMS ) of the premotor cortex/dorsolateral prefrontal cortex ( PMC/DLPFC ) can change thermal pain threshold toward analgesia in healthy subjects and has analgesic effects in acute postoperative pain as well as in fibromyalgia patients . However , its effect on neuropathic pain and in CPSP , in particular , has not been assessed . The aim of this prospect i ve , double-blind , placebo-controlled study was to evaluate the analgesic effect of PMC/DLPFC rTMS in CPSP patients . Patients were r and omized into 2 groups , active ( a- ) rTMS and sham ( s- ) rTMS , and were treated with 10 daily sessions of rTMS over the left PMC/DLPFC ( 10 Hz , 1,250 pulses/d ) . Outcomes were assessed at baseline , during the stimulation phase , and at 1 , 2 , and 4 weeks after the last stimulation . The main outcome was pain intensity changes measured by the visual analog scale on the last stimulation day compared to baseline . Interim analysis was scheduled when the first half of the patients completed the study . The study was terminated because of a significant lack of efficacy of the active arm after 21 patients completed the whole treatment and follow-up phases . rTMS of the left PMC/DLPFC did not improve pain in CPSP . PERSPECTIVE The aim of this double-blind , placebo-controlled study was to evaluate the analgesic effects of rTMS to the PMC/DLPFC in CPSP patients . An interim analysis showed a consistent lack of analgesic effect , and the study was terminated . rTMS of the PMC/DLPFC is not effective in relieving CPSP Objective : To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing . Methods : The efficacy of systemic lidocaine ( 5 mg/kg IV over 30 minutes ) was evaluated in a double-blind , placebo-controlled , and cross-over fashion , on both spontaneous ongoing pain and evoked pains ( allodynia and hyperalgesia ) in 16 patients with chronic poststroke ( n = 6 ) or spinal cord injury ( n = 10 ) related pain . Results : Lidocaine was significantly superior to the placebo ( saline ) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection : 10 of 16 patients ( 62.5 % ) receiving lidocaine showed a significant reduction in spontaneous pain , whereas only six patients showed this after the placebo . Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia , but was no better than the placebo against thermal allodynia and hyperalgesia . In general , the side effects were moderate and consisted mainly of lightheadedness ( 44 % ) . Conclusions : Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries . The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains Publisher Summary This chapter explores that spinal cord injury ( SCI ) has a number of severe and disabling consequences . Although loss of function is often considered the primary issue , pain is also a major problem . In central pain conditions , small r and omized trials have shown the effectiveness of amitriptyline and lamotrigine in central post-stroke pain and of dronabinol , a cannabinoid , in pain in multiple sclerosis . It is not known whether the efficacy of drugs in other central or peripheral neuropathic pain conditions can be anticipated to have similar effects in SCI neuropathic pain . Central neuropathic pain is often considered more refractory than peripheral neuropathic pain . It has been suggested that central post-stroke pain responds better to antidepressants than SCI pain . The chapter also review s that because of the lack of sufficient data in neuropathic SCI pain , efficacy in other neuropathic pain conditions has to be considered in choosing treatment Objective : We describe the frequency , duration , clinical characteristics , and radiologic correlates of central poststroke pain  ( CPSP ) in young ischemic stroke survivors in a prospect i ve study setting . Methods : A question naire of pain and sensory abnormalities and EQ-5D quality -of-life question naire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry . Patients ( n = 58 ) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT , Brief Pain Inventory , and Beck Depression Inventory question naires . Results : Of the included 824 patients , 49 had CPSP ( 5.9 % ) , 246 patients ( 29.9 % ) had sensory abnormality without CPSP , and 529 patients ( 64.2 % ) had neither sensory abnormality nor CPSP . The median follow-up time from stroke was 8.5 years ( interquartile range 5.0–12.1 ) . Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP ( p = 0.007 ) as well as to those with no sensory abnormality and no CPSP ( p < 0.001 ) . Forty ( 82 % ) of the patients with CPSP had concomitant other pain . CPSP was associated with moderate ( p < 0.001 ) and severe ( p < 0.001 ) stroke symptoms , but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups . Stroke localization was not correlated with CPSP . Conclusions : Late persistent CPSP was found in 5.9 % of young stroke survivors and was associated with concomitant other pain , impaired quality of life , and moderate or severe stroke symptoms Background Early rehabilitation after stroke is essential to help reduce disability . Purpose To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke . Data Sources English- language search es of multiple electronic data bases from April 2009 through July 2018 ; targeted search es to December 2018 for studies of selective serotonin reuptake inhibitors ( SSRIs ) or serotonin-norepinephrine reuptake inhibitors . Study Selection 19 systematic review s and 37 r and omized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke . Data Extraction One investigator abstract ed the data , and quality and GRADE assessment were checked by a second investigator . Data Synthesis Most interventions ( for example , SSRIs , mental practice , mirror therapy ) did not improve motor function . High- quality evidence did not support use of fluoxetine to improve motor function . Moderate- quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living ( ADLs ) . Low- quality evidence supported use of robotic arm training to improve ADLs . Low- quality evidence indicated that antidepressants may reduce depression , whereas the frequency and severity of antidepressant-related adverse effects was unclear . Low- quality evidence suggested that cognitive behavioral therapy and exercise , including mind-body exercise , may reduce symptoms of depression and anxiety . Limitation Studies were of poor quality , interventions and comparators were heterogeneous , and evidence on harms was scarce . Conclusion Cardiorespiratory training , repetitive task training , and transcranial direct current stimulation may improve ADLs in adults with stroke .  Cognitive behavioral therapy , exercise , and SSRIs may reduce symptoms of poststroke depression , but use of SSRIs to prevent depression or improve motor function was not supported . Primary Funding Source U.S. Department of Veterans Affairs , Veterans Health Administration Background and Purpose — Psychological stressors , including poststroke depression , poststroke anxiety , and posttraumatic stress disorder , are highly prevalent in stroke survivors . These symptoms exact a significant toll on stroke survivors . Clinical and research efforts in stroke recovery focus on motor disability , speech and language deficits , and cognitive dysfunction while largely neglecting psychological stressors . Evidence suggests mind-body interventions in other chronic illness population s decrease symptoms of depression , regulate immune responses , and promote resilience , yet similar studies are lacking in stroke population s. This review aims to synthesize evidence of the effects of mind-body interventions on psychological stressors , quality of life , and biological outcomes for stroke survivors . Methods — A systematic search of PubMed , PsycINFO , and CINAHL was conducted from data base inception to November 2017 . Results — Eight studies were included in the review , with a total of 292 participants .  Mind-body interventions included yoga or tai chi . Of the 5 included r and omized controlled trials , most were pilot or feasibility studies with small sample sizes . Psychological stressors , including poststroke depression and anxiety , along with the quality of life , improved over time , but statistically significant between-group differences were largely absent . The 3 included studies with a qualitative design reported themes reflecting improvement in psychological stressors and quality of life . No included studies reported biological outcomes . Conclusions — Studies of mind-body interventions suggest a possible benefit on psychological stressors and quality of life ; however , rigorously design ed , sufficiently powered r and omized controlled trials with mixed- methods design are warranted to delineate specific treatment effects of these interventions . Studies with both biological and psychological stressors as outcomes would provide evidence about interaction effects of these factors on stroke-survivor responses to mind-body interventions Objective : Central poststroke pain ( CPSP ) is usually difficult to treat . Amitriptyline , the only oral preparation shown to be effective in a r and omized controlled trial , is often associated with a range of side effects related to the many mechanisms of actions of tricyclic antidepressants . We investigated the effect of lamotrigine , a drug that reduces neuronal hyperexcitability , on poststroke pain . Methods : Thirty consecutive patients with CPSP ( median age 59 years , range 37 to 77 ; median pain duration 2.0 years , range 0.3 to 12 ) from two centers participated in a r and omized , double-blind , placebo-controlled cross-over study . The study consisted of two 8-week treatment periods separated by 2 weeks of wash-out . The primary endpoint was the median value of the mean daily pain score during the last week of treatment while treated with 200 mg/d lamotrigine . Secondary endpoints were median pain scores while on lamotrigine 25 mg/d , 50 mg/d , and 100 mg/d ; a global pain score ; assessment of evoked pain ; areas of spontaneous pain ; and allodynia/dysesthesia . Results : Lamotrigine 200 mg/d reduced the median pain score to 5 , compared to 7 during placebo ( p = 0.01 ) in the intent-to-treat population of 27 patients . No significant effect was obtained at lower doses . Twelve patients ( 44 % ) responded to the treatment . There was a uniform tendency to reduction of all secondary outcome measures , but lamotrigine only had significant effects on some of the secondary outcome measures . Lamotrigine was well tolerated with few and transient side effects . Two mild rashes occurred during lamotrigine treatment , one causing withdrawal from study . Conclusions : Oral lamotrigine 200 mg daily is a well tolerated and moderately effective treatment for central poststroke pain . Lamotrigine may be an alternative to tricyclic antidepressants in the treatment of CPSP 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 UNLABELLED Neuropathic pain in patients with MS is frequent and is associated with a great interference with daily life activities . In the present study , we investigated whether anodal transcranial direct current stimulation ( tDCS ) may be effective in reducing central chronic pain in MS patients . Patients received sham tDCS or real tDCS in a 5-day period of treatment in a r and omized , double blind , sham-controlled study . Pain was measured using visual analog scale ( VAS ) for pain and the short form McGill question naire ( SF-MPQ ) . Quality of life was measured using the Multiple Sclerosis Quality of Life-54 scale ( MSQoL-54 ) . Depressive symptoms and anxiety were also evaluated as confounding factors using the Beck Depression Inventory ( BDI ) and VAS for anxiety . Evaluations were performed at baseline , immediately after the end of treatment , and once a week during a 3-week follow-up period . Following anodal but not sham tDCS over the motor cortex , there was a significant pain improvement as assessed by VAS for pain and McGill question naire , and of overall quality of life . No depression or anxiety changes were observed . Our results show that anodal tDCS is able to reduce pain-scale scores in MS patients with central chronic pain and that this effect outlasts the period of stimulation , leading to long-lasting clinical effects . PERSPECTIVE This article presents a new , noninvasive therapeutic approach to chronic , central neuropathic pain in multiple sclerosis , poorly responsive to current conventional medications . tDCS is known to cause long-lasting changes of neuronal excitability at the site of stimulation and in the connected areas in healthy subjects . This led us to hypothesize that pain decrease may be the result of functional plastic changes in brain structures involved in the pathogenesis of chronic neuropathic pain BACKGROUND In recent years , local muscle vibration received considerable attention as a useful method for muscle stimulation in clinical therapy . Some studies described specific vibration training protocol , and few of them were conducted on post-stroke patients . Therefore there is a general uncertainty regarding the vibrations protocol . AIM The aim of this study was to evaluate the effects of local muscle high frequency mechano-acoustic vibratory treatment on grip muscle strength , muscle tonus , disability and pain in post-stroke individuals with upper limb spasticity . DESIGN Single-blind r and omized controlled trial . SETTING Outpatient rehabilitation center . POPULATION Thirty-two chronic poststroke patients with upper-limb spasticity : 21 males , 11 females , mean age 61.59 years ±15.50 , time passed from stroke 37.78±17.72 months . METHODS The protocol treatment consisted of the application of local muscle vibration , set to a frequency of 300 Hz , for 30 minutes 3 times per week , for 12 sessions , applied to the skin covering the venter of triceps brachii and extensor carpi radialis longus and brevis muscles during voluntary isometric contraction . All participants were r and omized in two groups : group A treated with vibration protocol ; group B with sham therapy . All participants were evaluated before and after 4-week treatment with H and Grip Strength Test , Modified Ashworth Scale , QuickDASH score , FIM scale , Fugl-Meyer Assessment , Jebsen-Taylor H and Function Test and Verbal Numerical Rating Scale of pain . Outcomes between groups was compared using a repeated- measures ANOVA . RESULTS Over 4 weeks , the values recorded in group A when compared to group B demonstrated statistically significant improvement in grip muscle strength , pain and quality of life and decrease of spasticity ; P-values were < 0.05 in all tested parameters . CONCLUSIONS Rehabilitation treatment with local muscle high frequency ( 300 Hz ) vibration for 30 minutes , 3 times a week for 4 weeks , could significantly improve muscle strength and decrease muscle tonus , disability and pain in upper limb of hemiplegic post-stroke patients . CLINICAL REHABILITATION IMPACT Local muscle vibration treatment might be an additional and safe tool in the management of chronic poststroke patients , granted its high therapeutic efficiency , limited cost and short and repeatable protocol of use
Results suggested that all therapies had little to no effect on pain and other patient-important outcomes .
Our findings are inconsistent with major clinical practice guidelines ; the available evidence suggests no beneficial effects of any therapies that research ers have evaluated in r and omized controlled trials
BACKGROUND AND PURPOSE Central poststroke pain is a chronic neuropathic disorder that follows a stroke .
Current research on its management is limited , and no review has evaluated all therapies for central poststroke pain .