A refresher on peripheral neuropathy

Peripheral neuropathy—defined as damage to peripheral nerves—affects about 1% of adults worldwide. Its prevalence increases with age, affecting about 6%–10% of the population older than 60 years.More than 200 causes of peripheral neuropathy have been identified, with diabetes being the most common cause. Peripheral neuropathy may cause sensory, motor and autonomic symptoms that range in severity from mild toe numbness to debilitating symptoms requiring patients to use a wheelchair. Peripheral neuropathy is typically “length-dependent,” which means that symptoms appear in the longest nerve axons (toes) and progress proximally toward the knees and hands over time. The condition is typically symmetric, affecting sensory axons more than motor axons. Diabetic neuropathy is often associated with both sensory symptoms (e.g., pain, tingling or numbness, mild weakness) and autonomic symptoms (e.g., orthostatic hypotension). It accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes (e.g., Charcot-Marie-Tooth disease), toxic neuropathy from medications (e.g., chemotherapy agents such as cisplatin, paclitaxel, vincristine; amiodarone; HIV nucleotide reverse transcriptase inhibitors such as stavudine and zalcitabine), alcohol use disorder, vitamin deficiencies (e.g., vitamin B12, B6) and monoclonal gammopathies. The JAMA review includes a table of medication-induced neuropathies, including the frequency of occurrence, time of onset and characteristic features for each drug. Up to 27% of adults with neuropathy have no identifiable cause for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). For some patients, foot soaks in cool water and applying moisturizing cream to prevent skin drying are sufficient to manage neuropathic pain. Topical treatments such as capsaicin or lidocaine have variable effectiveness.First-line medications for neuropathic pain include gabapentin and pregabalin, serotonin norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine) and tricyclic antidepressants (e.g., amitriptyline, nortriptyline). At least a 50% reduction in pain was observed in 38% of patients with painful diabetic peripheral neuropathy receiving gabapentin 1200 mg daily. However, pain often persists despite medical management. Selection of therapy should take into consideration comorbidities, the adverse effect profile of the medication and interactions with concomitant medications. Addition of a second first-line agent from a different drug class may further improve neuropathic pain symptoms. The JAMA review includes a table of medications for treatment of neuropathic pain, including dosage regimens, efficacy and adverse effects.Given the limited efficacy of first-line medications, other antiseizure and antidepressant medications such as valproic acid and venlafaxine are often prescribed off label. Opioids are not recommended for treatment of neuropathic pain. Referral to a pain clinic that offers multidisciplinary approaches (behavioural therapy, medications and neurostimulation) may be beneficial for people with persistent neuropathic pain.The prognosis of peripheral neuropathy depends on the underlying cause. Complete reversal of nerve damage is uncommon, even in cases for which there are available treatments. Reference:Mauermann ML, Staff NP. Peripheral neuropathy. A review. JAMA 2025; published online November 17, 2025. (accessed November 18, 2025).

A refresher on peripheral neuropathy

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