Nerve pain (neuropathic pain) comes from damage to or malfunction of the nerves themselves — from causes like diabetes, shingles, injury, or chemotherapy — which is why it behaves differently from ordinary aches and often does not respond to standard painkillers. The NHS is explicit that "neuropathic pain does not usually get better with common painkillers, such as paracetamol and ibuprofen," so the treatments that actually work are mostly prescription-only and belong to two families of drugs that quiet overactive nerve signals. The NHS lists the main recommended (first-line) medicines as the anticonvulsants gabapentin and pregabalin and the antidepressants amitriptyline and duloxetine — the same classes the NIH's NIDDK names for diabetic nerve pain, along with the tricyclic nortriptyline and topical options such as lidocaine skin patches. A key honesty point from NIDDK: these medicines "can help with the pain, [but] they do not change the nerve damage," and treating the underlying cause (for example, keeping blood glucose near goal in diabetes) is what actually protects the nerves. Genuine over-the-counter options are limited — topical capsaicin cream and OTC lidocaine patches may ease localized nerve pain, but there is no proven OTC pill, and both the NHS and NIDDK note that ordinary OTC painkillers usually don't help. Opioids are not a first-line treatment: the NHS reserves tramadol for pain that hasn't responded to other treatments and warns it "can be addictive if taken for a long time." Whichever medicine a clinician chooses, doses are typically started low and increased slowly, and it's common to trial more than one before finding what helps.
For options we rate, we show our independent FDA recall-safety rating(0–100) — a signal GoodRx and Drugs.com don’t provide. Higher is safer.
Available without a prescription — follow each label.
capsaicin (low-concentration topical) Zostrix, Capzasin Topical counterirritant (chili-pepper extract) | An OTC cream, gel, or roll-on made from the compound that makes chili peppers hot; the NHS notes capsaicin is thought to work by "stopping the nerves sending pain messages to the brain." It's a genuine self-care option for localized nerve pain (a specific patch of skin) rather than widespread pain, and it usually has to be applied several times a day for weeks before any benefit. It commonly causes burning or stinging where applied — wash hands well and keep it away from eyes and broken skin. This is the low-strength OTC form; a much stronger 8% capsaicin patch is prescription-only and applied by a clinician. |
lidocaine (OTC topical, 4%) Aspercreme, Salonpas Topical local anesthetic | OTC patches, creams, and gels containing up to 4% lidocaine numb the skin over a painful area and can help focal nerve pain such as a small area of post-shingles pain. They act only where applied, so they suit localized rather than body-wide pain. Follow the Drug Facts label for how many patches and how long to wear them. A higher-strength 5% lidocaine patch is prescription-only. |
A doctor may prescribe these — not for self-treatment.
Neurontin Gabapentinoid anticonvulsant | One of the main first-line medicines the NHS recommends for neuropathic pain; also used for epilepsy and some anxiety conditions. It calms overactive pain-signaling nerves. Prescription-only — your doctor decides whether it fits and what dose, starting low and increasing gradually. Drowsiness and dizziness are common, and the dose is lowered in people with reduced kidney function. |
Lyrica Gabapentinoid anticonvulsant | A close relative of gabapentin and, per the NHS, one of the main first-line options for nerve pain; also used for epilepsy and anxiety. It works the same way — dampening excitable nerve signals — but is dosed differently. Prescription-only; your doctor decides suitability and dose. Common effects include dizziness, drowsiness, and swelling; kidney function affects dosing. |
Cymbalta SNRI antidepressant | A serotonin-norepinephrine reuptake inhibitor that the NHS lists among the first-line nerve-pain medicines; NIDDK lists it specifically among options for diabetic nerve pain, and it's also used for depression and some bladder problems. It eases pain through pain-modulating brain and spinal-cord pathways, separate from its mood effect. Prescription-only — a clinician decides if and when it's appropriate. |
amitriptyline Elavil (now usually generic) Tricyclic antidepressant (TCA) |
Because no single drug is best for everyone, clinicians match the medicine to the person. For nerve pain from diabetes, or when low mood coexists, duloxetine is often favored (NIDDK lists it for diabetic nerve pain and it also treats depression). A tricyclic like amitriptyline or nortriptyline, taken at night, can be helpful when poor sleep is part of the picture, but its anticholinergic effects (dry mouth, constipation, drowsiness) and cardiac cautions make doctors careful in older adults and people with heart disease — nortriptyline is sometimes chosen as the better-tolerated tricyclic. The gabapentinoids gabapentin and pregabalin are common choices, cause dizziness and drowsiness, and need dose adjustment when kidney function is reduced. When pain is confined to one area — for example a patch of post-shingles pain — a clinician may add or prefer a topical (lidocaine or capsaicin) to avoid whole-body drug effects. Across all of these, the NHS approach is to start at a low dose and increase gradually until there's an effect, and it's normal to trial more than one medicine before finding one that helps enough. Two honesty points guide the whole plan: these medicines relieve pain but don't repair the nerve, so treating the underlying cause (such as blood-glucose control in diabetes) matters, and ordinary OTC painkillers usually don't relieve true nerve pain. All of the prescription options are decisions your doctor makes with you — this is information about how those choices are weighed, not a recommendation to start, stop, or pick any drug yourself.
See a doctor to have new or ongoing nerve pain evaluated — pinning down the cause (diabetes, shingles, a trapped or injured nerve, a vitamin deficiency, a medication) is what guides both treatment and protecting the nerve. Seek urgent or emergency care for red-flag signs: sudden or rapidly spreading weakness or numbness; numbness around the genitals/buttocks or new loss of bladder or bowel control (possible cauda equina — a medical emergency); a painful blistering rash (possible shingles, where early antiviral treatment helps); or, if you have diabetes and reduced feeling in your feet, any new sore, blister, ulcer, redness, or signs of infection, since these can worsen unnoticed. Also check back with your clinician if pain is disrupting sleep or daily life, is getting worse despite treatment, or if a medicine causes troubling side effects — doses often need adjusting and it can take trying more than one option. Living with chronic pain can weigh heavily on mental health; if you ever have thoughts of harming yourself, call or text the 988 Suicide & Crisis Lifeline (call or text 988) for free, confidential support available 24/7, and call 911 or go to an emergency room if you are in immediate danger.
General reference, not medical advice, and not a substitute for your doctor or pharmacist. The right choice depends on your symptoms, health conditions, age, and other medicines — always read each label and confirm before taking anything.
| An older antidepressant that the NHS names as a main first-line nerve-pain medicine, used at lower doses than for depression; NIDDK also lists it for diabetic nerve pain. Often taken at night because it can aid sleep. Prescription-only; a doctor weighs its anticholinergic side effects (dry mouth, constipation, drowsiness) and uses it cautiously in older adults and people with heart conditions. |
Pamelor Tricyclic antidepressant (TCA) Our rating 70/100 | A tricyclic closely related to amitriptyline and listed by NIDDK for diabetic nerve pain; it's sometimes chosen because it can be better tolerated (fewer sedating/anticholinergic effects) than amitriptyline. Prescription-only — the choice between TCAs is one a clinician makes based on your other conditions and side-effect tolerance. |
Lidoderm Topical local anesthetic | A higher-strength lidocaine skin patch — NIDDK lists topical lidocaine "skin creams, patches, or sprays" among nerve-pain options. It numbs a defined painful area and is typically used for localized nerve pain such as post-shingles (postherpetic) pain, avoiding whole-body drug effects. Prescription-only; a clinician decides placement and how long to wear it. |
Qutenza High-concentration topical capsaicin | A concentrated capsaicin patch applied by a healthcare professional in a clinic (not the OTC cream), used for certain localized neuropathic pain such as post-shingles pain or nerve pain in the feet. A single application can give relief lasting weeks to months. Prescription-only and clinician-applied because the high strength causes intense burning during treatment. |
Ultram, ConZip Opioid analgesic Our rating 72/100 | Not a first-line treatment. The NHS describes tramadol as "a powerful painkiller related to morphine" that a GP may use only for nerve pain that hasn't responded to other treatments, and "usually only prescribed for a short time" because it "can be addictive if taken for a long time." Prescription-only and a controlled substance — reserved for specific situations a doctor judges. |