What is the recommended evaluation and management of central pain syndrome?

Central Pain Syndrome: Evaluation and Management

Diagnostic Confirmation

Central pain syndrome must be confirmed by establishing that pain began after a cerebrovascular event or CNS injury and is localized to the neuroanatomical region corresponding to the lesion, while actively excluding nociceptive and peripheral neuropathic sources. 1, 2

• Look for characteristic sensory disturbances including burning sensations, allodynia (pain from light touch), cold-induced pain, and dysesthesia in a glove-and-stocking or hemibody distribution. 1
• Onset typically occurs within days to one month after the stroke or CNS injury, though it can emerge months to years later, which often obscures recognition. 1, 3
• Central post-stroke pain affects 2-8% of stroke patients and results from damage to the spinothalamic tract. 4, 2, 5
• Track treatment response using standardized instruments such as pain diaries, visual analogue scales, or validated pain questionnaires—not subjective impressions. 1

Common diagnostic pitfall: Central pain is frequently underdiagnosed or misattributed to musculoskeletal or visceral pain; do not attribute all post-stroke pain to central mechanisms without excluding hemiplegic shoulder pain, spasticity-related discomfort, or other serious causes. 2, 5, 3

First-Line Pharmacological Treatment

Amitriptyline 75 mg at bedtime is the primary recommended agent for central post-stroke pain, supported by the strongest evidence from the American Heart Association and American Academy of Neurology. 1, 6

• Amitriptyline reduces daily pain intensity and improves global functioning in central pain syndromes. 1
• Be cautious with anticholinergic side effects (dry mouth, constipation, urinary retention, confusion) particularly in elderly patients. 2

Alternative first-line options when amitriptyline is contraindicated or poorly tolerated:

• Gabapentin or pregabalin are endorsed by Canadian stroke guidelines as first-line alternatives. 4, 2, 5
• Pregabalin shows mixed efficacy for pain reduction but consistently improves sleep quality and anxiety symptoms, which are commonly impaired in stroke patients. 1, 5
• Gabapentin lacks stroke-specific trial data but is effective for other neuropathic pain conditions, supporting its use by extrapolation. 1, 5

Second-Line Pharmacological Options

When first-line agents fail or are not tolerated, use serotonin-norepinephrine reuptake inhibitors (SNRIs), particularly duloxetine, or lamotrigine. 1, 2

• Duloxetine and other SNRIs are recommended as second-line agents by Canadian guidelines. 4, 2
• Lamotrigine can lower daily pain scores and diminish cold-induced pain, but only 44% of patients achieve a good clinical response, indicating modest efficacy. 1, 2, 5

Third-Line Treatment for Refractory Pain

Opioids (including tramadol) may be employed only for patients with pain refractory to multiple prior agents, but use must be highly restricted due to significant risk of physical dependence. 4, 1, 2

• Reserve opioids for those who have exhausted other options, as evidence for long-term efficacy in central pain is limited. 4, 1
• All patients on long-term opioid therapy develop physical dependence; taper dosages gradually when discontinuing and instruct patients never to stop abruptly. 4
• Patients with active or previous substance abuse and family history of substance abuse are at higher risk for misuse. 4

Non-Pharmacological Adjuncts

Integrate therapeutic exercise and psychosocial support with medication, as central pain has multidimensional components affecting mood, sleep, and function. 1, 2, 5

• Implement an interdisciplinary team approach that includes mental health specialists and central pain experts to manage comorbid depression, anxiety, and sleep disturbances. 4, 1, 2
• For spasticity-related pain (a distinct entity from central neuropathic pain), begin with antispastic positioning, range of motion exercises, stretching, splinting, and serial casting before pharmacotherapy. 2, 5

Interventional Therapy for Intractable Pain

Motor cortex stimulation is a viable option for patients with pain unresponsive to pharmacotherapy, yielding ≥50% pain reduction in 50-83% of carefully selected individuals with benefits lasting up to two years. 1, 2, 5

• Notable risks include infection, hardware malfunction, postoperative seizures, and potential development of long-term epilepsy. 1
• This should be reserved for intractable cases after exhausting pharmacological options. 2, 5

Contraindicated Interventions

Transcutaneous electrical nerve stimulation (TENS) has demonstrated no analgesic benefit in small trials and should not be used for central post-stroke pain. 1, 2, 5

Monitoring and Realistic Expectations

Therapy must be adjusted based on specific pain characteristics, comorbid conditions, and observed response using serial standardized assessments. 1

• Recognize that complete pain resolution is uncommon; partial relief often represents a realistic therapeutic goal. 1
• Patients with central neuropathic pain managed in tertiary care centers are less likely to achieve meaningful improvement compared to those with peripheral neuropathic pain (9.6% vs 25.3% achieving ≥30% pain reduction and ≥1 point reduction in pain interference at 12 months). 7
• Central pain syndromes are relatively more refractory to treatment than peripheral neuropathic pain based on clinical trials and experience. 4