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NEW Delivery Of Stroke Rehabilitation to Optimize Functional Recovery
NEW Delivery Of Stroke Rehabilitation to Optimize Functional Recovery

9. Central Pain

Recommendations and/or Clinical Considerations
  1. An individualized approach for management of central pain syndrome should be implemented by an interdisciplinary team that includes healthcare professionals with expertise in mental health and central pain management [Strong recommendation; Low quality of evidence]. 
  2. Individuals with stroke should be assessed for central pain. The diagnosis of central post-stroke pain should be based on established diagnostic criteria after other causes of pain have been excluded [Strong recommendation; Moderate quality of evidence].
  3. Individuals with persistent Central Post-Stroke Pain (CPSP) should receive a trial of low-dose, centrally acting analgesics [Strong recommendation; High quality of evidence]. 
    1. Individuals should receive a gabapentinoid class of anticonvulsant (e.g., gabapentin or pregabalin) as a first-line treatment for central nervous system pain [Strong recommendation; High quality of evidence]. 
    2. Other pharmacological treatment options that may be considered in the treatment of central pain include tricyclic antidepressants (e.g., amitriptyline), or a serotonin and norepinephrine reuptake inhibitors (SNRI) (particularly duloxetine) [Strong recommendation; Moderate level of evidence].  
Rationale +-

Post-stroke central pain is a complex condition that can arise from damage to the spinothalamic tract (STT) of the central nervous system, often resulting in chronic pain that is difficult to manage. It reportedly affects 2% to 5% of stroke patients and complete resolution of the pain is challenging to achieve. 213 This type of pain typically manifests as a burning, aching, or tingling sensation in the affected areas and can significantly interfere with an individual with stroke’s daily activities, interfere with sleep, and reduce overall quality of life. Individuals may experience heightened sensitivity to touch or temperature, complicating their ability to perform rehabilitation exercises and engage in everyday tasks. The unpredictability and intensity of central pain can lead to emotional distress, contributing to depression and anxiety. Effective management often requires an interdisciplinary approach, including medication, physical therapy, and psychological support, to alleviate symptoms and improve the overall well-being of those affected.

Individuals with stroke stress the importance of education on central post-stroke pain, including information for family members and caregivers. This education may include information to self-monitor and recognize potential symptoms as well as the dosing, timing, and contraindications of medications. Individuals with stroke appreciate an individualized and person-centred approach for the management of central pain that values their choices and autonomy.

Performance Measures +-

System Indicators

  1. Availability of inpatient and community-based education and resources for individuals with stroke experiencing central pain.
  2. Proportion of individuals central pain issues following an acute stroke.

Process Indicators

  1. Proportion of individuals with stroke experiencing central pain who receive a comprehensive assessment by appropriately trained healthcare professionals.
  2. Proportion of individuals with stroke experiencing central pain who receive comprehensive treatment and an ongoing management plan by appropriately trained healthcare professionals.

Patient-Oriented Indicators   

  1. Changes in pain ratings from initiation of treatment, measured weekly, using standardized pains scales.
  2. Changes in quality of life of individuals with stroke who experience central pain syndrome, measured using a standardized scale and at regular follow-up intervals.
Implementation Resources and Knowledge Transfer Tools +-

Resources and tools listed below that are external to Heart & Stroke and the Canadian Stroke Best Practice Recommendations may be useful resources for stroke care. However, their inclusion is not an actual or implied endorsement by the Canadian Stroke Best Practices team or Heart & Stroke. The reader is encouraged to review these resources and tools critically and implement them into practice at their discretion.

Health Care Provider Information

Resources for Individuals with Stroke, Families and Caregivers 

Summary of the Evidence +-

Evidence Table and Reference List 9

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 occurs in an estimated 2% to 5% of all stroke cases. 213 The literature on the treatment of CPSP is sparse.

Anticonvulsants (gabapentin, pregabalin), anti-seizure medications (lamotrigine) and antidepressants including tricyclic antidepressants (TCA), serotonin–norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors are the most frequently drugs for the treatment of neuropathic pain, although there is little published evidence of their effectiveness in CPSP. Most recently, Mahesh et al.214 randomized 82 patients diagnosed with CPSP within the first 60 days post stroke to receive 30 mg duloxetine or placebo daily for 4 weeks. The dose was doubled if there was no response to treatment at two weeks. There were significantly greater reductions in the mean numeric pain intensity (NPI) score at the end of treatment in the duloxetine group (6.51 to 3.02 vs. 6.37 to 4.40, p=0.02), Short-form McGill Pain Questionnaire-2 scores (19.5 to 8.85 vs. 20.3 to 13.3, p=0.032) and the Pain Disability Index (PDI) score (42.95 to 24.18 vs. 42.05 to 30.05, p=005). Adverse events including dizziness, somnolence, and nausea were reported more frequently in the duloxetine group. Vranken et al. 215 randomized 48 patients with severe neuropathic pain resulting from cerebrovascular lesions (n=12) or spinal cord lesions to receive escalating doses of either duloxetine (60 and 120 mg/day) or placebo for 8 weeks. At the end of treatment, the mean pain scores, assessed using a 10-point visual analogue scale (VAS) were reduced from 7.1 to 5.0 (duloxetine) vs. 7.2 to 6.1 (placebo), although the result was not statistically significant (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 subsection of the 36-Item Short Form Survey (p=0.035). In an uncontrolled study, Kim et al. 216 reported that the addition of 30 to 60 mg duloxetine to concurrent pain medications helped to reduce Numeric Rating Scale pain scores by 30% in 70% of 37 patients with CPSP with chronic onset (mean 3.1 years)

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. 217 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. 218 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 VAS (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 PDI scores between groups. Serpell et al. 219 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 2,400 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 evaluated the potential benefit of the anti-epileptic agent, levetiracetam in patients with CPSP. Jungehulsing et al. 220 included 42 patients with CPSP, 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 3,000 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.

Sex & Gender Considerations

No evidence was reviewed suggestive of sex or gender differences in the frequency CPSP or response to treatment.

Stroke Resources
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