What medications are useful for alleviating nerve pain and numbness associated with a history of right lacunar infarction (stroke)?

Management of Post-Stroke Neuropathic Pain

For excruciating nerve pain following lacunar stroke, start with amitriptyline 10-75 mg at bedtime as first-line therapy, or alternatively lamotrigine if amitriptyline is contraindicated, based on the strongest evidence for central post-stroke pain. 1

First-Line Pharmacological Options

Amitriptyline (Preferred Initial Agent)

• Start at 10 mg daily at bedtime, titrating up to 75 mg/day as tolerated 2, 1
• Demonstrated efficacy in lowering daily pain ratings and improving global functioning in central post-stroke pain 1
• Use caution in elderly patients and those with cardiovascular disease; obtain ECG if PR or QTc interval prolongation is suspected, as doses >100 mg/day are associated with increased risk of sudden cardiac death 2
• Common side effects include drowsiness and anticholinergic effects (dry mouth, constipation, urinary retention) 2, 1

Lamotrigine (Alternative First-Line)

• Effective for reducing daily pain ratings and cold-induced pain in central post-stroke pain 1
• Note that only 44% of patients achieve good clinical response 1
• Choose lamotrigine over amitriptyline if patient has cardiac contraindications or cannot tolerate anticholinergic side effects 1

Second-Line Options When First-Line Fails

Duloxetine (SNRI)

• Dose: 60-120 mg/day 2
• Approximately 50% of patients achieve at least 50% pain reduction 2
• Advantages include antidepressant effects and no weight gain 2
• Most frequent adverse effects are nausea, somnolence, dizziness, constipation, and dry mouth (typically mild to moderate and transient) 2

Gabapentin

• Start at 300 mg on day 1, increase to 600 mg on day 2, then 900 mg on day 3; titrate to 1800-3600 mg/day in divided doses 3
• Established efficacy for neuropathic pain, though specific evidence for central post-stroke pain is limited 2, 4, 3
• Adverse effects typically mild to moderate and subside within approximately 10 days 3

Pregabalin

• Dose: 150-600 mg/day in divided doses 2, 5
• While effective for peripheral neuropathic pain, a large randomized trial showed no significant difference in pain reduction compared to placebo for central post-stroke pain (mean pain score reduced from 6.5 to 4.9 vs 6.3 to 5.0 with placebo, P=0.578) 6
• However, pregabalin did show significant improvements in sleep quality, anxiety, and clinician global impression of change 6
• Consider pregabalin specifically if pain-related sleep disturbance and anxiety are prominent features 7, 6

Important Clinical Considerations

Combination Therapy Approach

• If monotherapy provides inadequate relief, combine medications acting on different pathways 2
• Gabapentin plus extended-release morphine or oxycodone requires lower doses of each medication and provides better pain relief than either alone 2
• Nortriptyline plus gabapentin is superior to either medication alone 2
• Pregabalin can be combined with transcutaneous electrical nerve stimulation (TENS) for enhanced effect 8
• Gabapentin and pregabalin can be used together for synergistic effect, allowing dose reduction of individual agents and minimizing side effects 9

Critical Pitfalls to Avoid

• Do not assume all facial and arm pain is neuropathic; confirm it corresponds to the stroke lesion location and cannot be explained by other causes 1
• Avoid benzodiazepines (diazepam) during stroke recovery due to deleterious effects on recovery and sedation 10
• Do not use TENS as monotherapy; it has been shown ineffective in small trials 1
• Be particularly cautious with anticholinergic effects of amitriptyline in elderly stroke patients 1

Refractory Pain Management

• For intractable central post-stroke pain unresponsive to pharmacotherapy, motor cortex stimulation may be considered in carefully selected patients 1
• Motor cortex stimulation achieves >50% pain reduction in 50-83% of patients for up to 2 years 1

Non-Pharmacological Adjuncts

• Combine pharmacotherapy with therapeutic exercise and psychosocial support 10
• Consider physical therapy, range of motion exercises, and positioning strategies as adjunctive measures 10

Medication Titration Strategy

• Allow at least 2 weeks at appropriate therapeutic dose before declaring treatment failure and switching agents 2
• Titrate slowly to minimize adverse effects and improve tolerability 2
• If first-line agent fails, switch to the alternative first-line option before moving to second-line agents 2, 1