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Rehabilitation to Improve Central Pain

2016 UPDATE
February 2016

The Canadian Stroke Best Practice Recommendations for Stroke Rehabilitation, 5th Edition (2015) is published in the International Journal of Stroke (IJS) and available freely online. To access the specific recommendations for Rehabilitation to Improve Central Pain, and all other sections of the Stroke Rehabilitation recommendations, please click on this URL which will take you to the recommendations online in the IJS: http://journals.sagepub.com/doi/pdf/10.1177/1747493016643553

For the French version of these recommendations, open the appendix at this link :  http://wso.sagepub.com/content/suppl/2016/04/18/1747493016643553.DC1/Stroke_Rehabilitation_2015_IJS_Manuscript_FINAL_FRENCH.pdf

All other supporting information, including performance measures, implementation resources, evidence summaries and references, remain available through www.strokebestpractices.ca, and not through the IJS.  Please click on the appropriate sections on our website below for this additional content.

Rationale

Central post-stroke pain (CPSP) is a rare neurological disorder in which the body becomes hypersensitive to pain as a result of damage to the spinothalamic tract (STT), although not all damage to the STT produces CPSP. It reportedly affects 2% to 5% of stroke patients. With involvement of the STT, patients have loss of temperature and pain sensation in the involved area. It is most commonly associated with lesions to the ventrocaudal nucleus of the thalamus but has been reported in brainstem lesions where there is damage to the STT. The primary symptoms are pain and loss of sensation, usually in the face, arms, and/or legs. Pain or discomfort may be felt after being mildly touched or even in the absence of a stimulus. The pain may worsen by exposure to heat or cold and by emotional distress. CPSP can dramatically hinder a patient’s ability to perform ADLs, interfere with sleep and reduce quality of life.

System Implications

  • Inclusion of central pain assessments as part of standard screening and assessment protocols for stroke rehabilitation
  • Access to specialized services for management of central pain

Performance Measures

  1. Changes in pain ratings from initiation of treatment, measured weekly, using standardized pains scales.
  2. Changes in quality of life of stroke patients who experience central pain syndrome, measured using a standardized scale and at regular follow-up intervals.

Implementation Resources and Knowledge Transfer Tools

Health Care Provider Information

Patient Information

Summary of the Evidence

Evidence Table 9: Rehabilitation to Improve Central Pain

Central post-stroke pain (CPSP) is a rare neurological disorder, in which the body becomes hypersensitive to pain as a result of damage to the thalamus, the part of the brain that affects sensation. The condition is rare, occurring in an estimated 2% to 5% of all stroke cases. Antidepressants including tricyclic antidepressants, serotonin–norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors are used most frequently for the treatment of neuropathic pain, although there is little published evidence of their effectiveness in CPSP. Vranken et al. (2011) randomized 48 patients with severe neuropathic pain resulting from cerebrovascular lesions or spinal cord lesions to receive escalating doses of either duloxetine (60 and 120mg/day) or placebo for 8 weeks. There was a trend towards reduction in pain associated with duloxetine treatment. At the end of treatment, the mean pain scores, assessed using a 10-point visual analogue scale were reduced from 7.1 to 5.0 (duloxetine) vs. 7.2 to 6.1 (placebo), p=0.06. There were no differences between groups in Patient Disability Index or EQ-5D scores but patients in the duloxetine group reported better pain scores on the bodily pain sub section of the SF-36 (p=0.035).

Several RCTs have been published evaluating the effectiveness of the anticonvulsant drugs, pregabalin and gabapentin. The majority of these studies have included patients with neuropathic pain of varying etiology. A single RCT included patients who were suffering exclusively from CPSP. In this study (Kim et al. 2011) randomized 220 patients to receive either 150-600 mg of pregabalin or placebo over 13 weeks. At the end of treatment the mean pain scores were reduced from 6.5 to 4.9 in the pregabalin group and from 6.3 to 5.0 in the placebo group, although the difference was not statistically significant. (p=0.578). Treatment with pregabalin resulted in significant improvements, compared with placebo, on secondary endpoints including some aspects of sleep, anxiety (Hospital Anxiety & Depression Scale-A), and clinician global impression of change (p<0.05). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation of treatment in 9 (8.2%) patients compared with 4 (3.7%) of placebo patients. Vranken et al. (2008) randomized 40 patients (19 with stroke) suffering from severe neuropathic pain, to receive a 4-week course of treatment with escalating doses of pregabalin (max 600 mg/day) or placebo. At the end of treatment, patients in the pregabalin group experienced significantly greater pain relief on a 10-point visual analogue scale (mean=7.6 to 5.1 vs. 7.4 to 7.3, p=0.01) and had significant improvement in EQ-5D scores and in the bodily pain domain of the SF-36. There was no significant difference in Pain Disability Index scores between groups. Serpell et al. (2002) randomized 307 patients with a wide range of neuropathic pain syndromes (9 with post stroke pain) to receive either gabapentin or placebo for 8-weeks. Gabapentin was given in three divided doses to a maximum of 2400 mg/day. Patients in the treatment group experienced a significantly greater reduction in pain over the study period (mean reduction of 21% vs. 14%, p=0.048). Significant differences were shown in favour of gabapentin for the clinician and patient Global Impression of Change Scale, and some domains of the Short Form-McGill Pain Questionnaire.

One RCT has been published evaluating levetiracetam (LEV) in a CPSP population. Jungehulsing et al. (2013) studied 42 patients with a diagnosis of CPSP of duration greater than 3 months from a stroke with a score of 4 or greater on a numeric Likert scale for pain intensity (range 0-10). Participants were randomized to either: an intervention group; LEV at a maximum dose of 3000 mg or a control (placebo) group for 24 weeks which consisted of a 4-week baseline period, followed by two 8-week treatment periods each followed by a 2-week washout period. Compared to controls, LEV did not show an improvement in spontaneous or evoked pain, or any of the secondary measures including McGill Pain Questionnaire, revised Beck Depression Inventory, Short Form-12 Health Survey (p>0.05 for all). Side-effects in the first treatment period included tiredness, pain increased, dizziness, pruritus, nausea, and headache in the LEV group compared to controls (p<0.05).