Methotrexate and Neuropathy: How to Spot and Manage Nerve Pain

Worried your methotrexate might be causing numbness, tingling, or burning in your hands or feet? Methotrexate can be linked to nerve problems, but that’s rare. Still, knowing the signs and the steps to take makes a big difference.

What to watch for

Common symptoms include pins-and-needles, burning pain, numbness, weakness, or balance problems. Symptoms may show up weeks to months after starting or changing dose. If you feel one-sided severe weakness, sudden loss of coordination, or bladder/bowel problems, contact your doctor right away.

Not all neuropathy in someone taking methotrexate is caused by the drug. Other causes include diabetes, B12 deficiency, thyroid problems, alcohol use, or other medications. That’s why testing matters before making treatment changes.

How doctors check it

Start with a focused exam and basic labs: B12, TSH, fasting glucose or A1c, liver and kidney tests, and folate levels. If those don’t explain symptoms, nerve conduction studies (NCS/EMG) can find large-fiber damage. For burning pain with normal NCS, a skin biopsy or specialized tests can show small-fiber neuropathy.

Talk with your prescribing clinician and consider a neurology referral when symptoms are persistent or worsening. Early evaluation helps avoid lasting nerve damage.

Management often begins with simple steps. Most doctors recommend folic acid or folate with methotrexate; this lowers some side effects and may help prevent deficiency-related nerve problems. Don’t stop methotrexate on your own—ask your prescriber about dose changes or switching drugs.

For pain control, first-line drugs for neuropathic pain include gabapentin, pregabalin, and duloxetine. Tricyclic antidepressants like amitriptyline work for some people but have more side effects. Topical options—lidocaine patches or capsaicin—can help focused areas. If you take vitamin B6, keep doses moderate: very high B6 can itself cause neuropathy.

Non-drug strategies matter too. Physical therapy can improve balance and strength. Regular gentle exercise helps nerve health and reduces pain for many people. Use shoes with good support, make home changes to avoid falls, and try TENS or other nerve-stimulating therapies if recommended by your clinician.

Monitoring is simple: report new numbness, tingling, or weakness right away. Your doctor may repeat labs, adjust methotrexate, or order nerve testing. Keep a symptom diary—note when symptoms started, triggers, and how they change.

If you notice signs of neuropathy, don’t wait. Talk to your prescriber about testing and treatment, ask about folate if you’re not already taking it, and consider a neurology consult when symptoms persist. Early action gives the best chance to control pain and protect nerve function.