What is the optimal treatment for neuropathic pain in a 40‑year‑old male with a traumatic forearm nerve injury repaired a year ago, now worsened after overuse and with normal imaging?

Treatment of Post-Traumatic Neuropathic Pain After Tendon Repair

Start duloxetine 30 mg daily for one week, then increase to 60 mg daily, and if partial relief occurs after 2-4 weeks, add pregabalin 75 mg twice daily, titrating to 150 mg twice daily over 1-2 weeks. 1, 2

First-Line Pharmacologic Treatment

Duloxetine is the optimal initial choice for this patient with post-traumatic nerve injury because it has the strongest evidence for neuropathic pain (59% pain reduction versus 38% placebo), improves quality of life, and has fewer side effects than tricyclic antidepressants. 1, 2

• Begin duloxetine at 30 mg once daily for the first week to minimize nausea, then increase to the target dose of 60 mg once daily. 1, 2
• Maximum dose can be increased to 120 mg/day if needed after 4 weeks at 60 mg/day. 2
• Allow at least 2-4 weeks at the therapeutic dose (60 mg) before declaring treatment failure. 1, 2
• Common side effects include nausea (minimized by starting at 30 mg), somnolence, dizziness, constipation, and dry mouth, but these are typically mild and transient. 2
• Unlike tricyclic antidepressants, duloxetine does not require ECG monitoring and has no significant cardiac risks. 2

Second-Line: Add Pregabalin for Partial Response

If duloxetine provides only partial relief after 2-4 weeks, add pregabalin rather than switching medications. 2 Combination therapy targeting different neurotransmitter systems (serotonin-norepinephrine reuptake inhibition plus voltage-gated calcium channel blockade) provides superior pain relief compared to either medication alone. 1, 2

• Start pregabalin at 75 mg twice daily (or 50 mg three times daily if concerned about tolerability). 2, 3
• After one week, increase to 150 mg twice daily (300 mg/day total). 2, 3
• Maintain 150-300 mg/day for at least 2-4 weeks before assessing combined efficacy. 1, 2
• Maximum dose is 600 mg/day, but most patients achieve adequate control with 150-300 mg/day; higher doses add side effects without proportional benefit. 2, 3
• Monitor for peripheral edema, particularly since this patient performs manual farm labor. 2

Alternative First-Line Option: Tricyclic Antidepressants

If duloxetine is contraindicated or not tolerated, use nortriptyline or desipramine (not amitriptyline) because secondary-amine tricyclics have fewer anticholinergic effects while maintaining strong efficacy (NNT = 2.64-3.6). 1, 2

• Start nortriptyline 10-25 mg at bedtime and titrate slowly to 75-150 mg/day over 2-4 weeks. 1, 2
• Obtain a screening ECG before starting if patient is over 40 years old. 1, 2
• Avoid in patients with recent myocardial infarction, arrhythmias, heart block, or significant cardiac disease. 1, 2
• Common side effects include dry mouth, orthostatic hypotension, constipation, and urinary retention; cardiac toxicity is the most serious concern. 2

Topical Adjunctive Therapy for Localized Pain

If pain is well-localized to the forearm injury site, add 5% lidocaine patches regardless of systemic medication choice. 1, 2, 4

• Apply daily to the painful area with minimal systemic absorption, making this excellent for combination therapy. 2, 4
• Lidocaine patches have an NNT of 2 for localized neuropathic pain and add minimal adverse effects when combined with gabapentinoids or antidepressants. 2, 4
• 8% capsaicin patches provide sustained relief for up to 12 weeks after a single 30-minute application and should be considered if lidocaine patches are insufficient. 2

Third-Line: Tramadol (Only After First-Line Failure)

Tramadol should only be considered after documented failure of duloxetine (or TCA) plus pregabalin combination therapy. 1, 2

• Start tramadol at 50 mg once or twice daily, with a maximum of 400 mg/day. 1, 2
• Tramadol has dual mechanism (weak μ-opioid agonist plus serotonin-norepinephrine reuptake inhibition) and lower abuse potential than strong opioids. 1, 2
• Exercise extreme caution if combining with duloxetine due to risk of serotonin syndrome. 2

Critical Treatment Principles and Common Pitfalls

The most common error is stopping medications too early. Post-traumatic neuropathic pain (particularly after nerve repair) is notably more refractory to treatment than other neuropathic conditions like diabetic neuropathy or postherpetic neuralgia. 2

• First-line agents must be continued at therapeutic doses for at least 2-4 weeks before declaring failure. 1, 2
• Ensure target doses are reached (duloxetine 60 mg/day, pregabalin 150-300 mg/day) before switching or adding medications. 1, 2
• Avoid strong opioids for long-term management due to risks of dependence, cognitive impairment, pronociception, and limited long-term efficacy in neuropathic pain. 2

Non-Pharmacologic Adjuncts (Essential, Not Optional)

Physical therapy and structured exercise must be incorporated immediately because they provide anti-inflammatory effects and improve pain perception through inhibition of pain pathways. 1, 2

• Cardio-exercise for at least 30 minutes twice weekly has been shown to reduce neuropathic pain symptoms. 2
• Physical therapy should focus on coordination, sensorimotor function, and gradual return to functional activities without overuse. 1
• An elastic compression sleeve on the forearm may help reduce pain by providing constant mechanical stimulation that modulates pain transmission. 2

Medications to Avoid

Do not use gabapentin as first-line therapy in this patient because lumbosacral radiculopathy and post-traumatic nerve injuries are more refractory to gabapentinoids compared to other neuropathic conditions, and pregabalin has superior pharmacokinetics. 2

• Avoid lamotrigine due to risk of serious rash (Stevens-Johnson syndrome) and lack of consistent benefit. 2
• Avoid clonidine, pentoxifylline, and mexiletine as they have been shown to be ineffective for neuropathic pain. 1

Treatment Algorithm Summary

1. Week 1: Start duloxetine 30 mg daily 1, 2
2. Week 2-4: Increase duloxetine to 60 mg daily; add 5% lidocaine patches if pain is localized 1, 2
3. Week 5-6: If partial response, add pregabalin 75 mg twice daily, increase to 150 mg twice daily after one week 1, 2
4. Week 7-10: Maintain combination therapy at therapeutic doses; assess efficacy 1, 2
5. If inadequate response: Consider switching duloxetine to nortriptyline (with ECG screening) or adding 8% capsaicin patches 1, 2
6. Last resort: Tramadol 50 mg twice daily only after documented failure of above combinations 1, 2

Throughout treatment, continue physical therapy and avoid overuse that precipitated the current exacerbation. 1, 2