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Rehabilitation and Recovery following Stroke

9. Management of Central Pain

6th Edition - 2019 UPDATED

  1. Patients with persistent Central Post Stroke Pain (CPSP) should receive a trial of low-dose, centrally acting analgesics [Evidence Level C]:
    1. Patients should receive an anticonvulsant (such as gabapentin or pregabalin) as a first-line treatment for central nervous system pain [Evidence Level C].
    2. Patients should receive a tricyclic antidepressant (e.g., amitriptyline) or an SNRI (particularly duloxetine) as second-line treatment [Evidence Level C].
    3. Treatment for patients resistant to first- and second-line treatment can include opioids or tramadol [Evidence Level C]. Caution is advised for the use of opioids as there is a significant risk of physical dependency.
  2. An individualized patient-centred approach for management of central pain syndromes should be implemented by an interdisciplinary team that includes healthcare professionals with expertise in mental health and central pain management [Evidence Level C].
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.


People with stroke provided feedback stressing the importance of family and caregiver education on CPSP.  Depending on the abilities of the person with stroke, family members and caregivers need training on the treatment of CPSP, including the dosing, timing, and contraindications of analgesics.  In addition, people with stroke require education on CPSP so they can self-monitor and recognize potential symptoms.  People with stroke value their choices and autonomy and appreciate when medications are offered and explained to them.

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
  • The development and implementation of an equitable and universal pharmacare program, implemented in partnership with the provinces, designed to improve access to cost-effective medicines for all people in Canada regardless of geography, age, or ability to pay. This program should include a robust common formulary for which the public payer is the first payer.
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
Summary of the Evidence +-

Evidence Table and Reference List


Central post-stroke pain (CPSP) is a rare neurological disorder, in which the body becomes hypersensitive to pain, resulting from 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. 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, most of which 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, on secondary endpoints including some aspects of sleep, anxiety and clinician global impression of change. Adverse events were more frequent with pregabalin causing the discontinuation of treatment in 8.2% of patients compared with 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 evaluating the potential benefit of the anti-epileptic agent, levetiracetam in patients with CPSP. Jungehulsing et al. (2013) included 42 patients with CPSP resulting from stroke, of duration greater than 3 months and a score of 4 or greater on 10-point pain intensity scale. Participants were randomized to receive levetiracetam at a maximum dose of 3000 mg or a placebo over a 24-week study period which included two, 8-week treatment periods. Treatment with levetiracetam was not associated with significantly greater improvement in spontaneous or evoked pain, or any of the secondary measures including the McGill Pain Questionnaire, revised Beck Depression Inventory, or the Short Form-12 Health Survey, with increased frequency of reported side-effects.


Stroke Resources