Traditional painkillers used alone, especially non-steroidal anti-inflammatory drugs (NSAIDs), are often ineffective at treating neuropathic pain.

The right combination of pain management strategies will help you function better and have a better quality of life. Treatments vary from person to person—it all depends on your pain and your needs.

What Causes Neuropathy?

This type of pain results from nerve damage. Damaged nerves become hyperexcitable and instead of merely processing pain signals, they will often start creating them.

Conditions involving neuropathic pain include:

Diabetic neuropathy Trigeminal neuralgia Migraine Myofascial pain Fibromyalgia Post-herpetic neuralgia Radiculopathy Central pain syndrome

Other conditions and factors that sometimes can lead to neuropathic pain include:

Cancer Chemotherapy Stroke (post-stroke central pain) HIV and other infections Injury Amputation

Adjuvant Analgesics

Analgesics are painkillers. Adjuvant analgesics are drugs created to treat other conditions that also happen to have an impact on some types of pain. Anticonvulsants and antidepressants, through their effects on the nervous system, can often combat neuropathic pain sensations.

Only a few of these drugs are specifically approved for neuropathic pain treatment, so most are used off-label. Don’t let that worry you, though. Many adjuvant analgesics have proven more effective at treating chronic nerve pain symptoms than traditional painkillers. The two main classes used for treating neuropathic pain are anticonvulsants and antidepressants.

Anticonvulsants

Also called anti-seizure or anti-epileptic drugs, anticonvulsants calm hyperexcited nerves and have long been used to treat painful neuropathy. Epilepsy and neuropathic pain actually share certain molecular changes that are involved in nerve hyperexcitability, which may help explain why these drugs are effective against both conditions.

Not all drugs in this class work the same way, and some work better than others for treating specific conditions. Some are approved by the Food and Drug Administration (FDA) for treating pain, while others are used off-label.

Anticonvulsants commonly prescribed for treating nerve pain include:

Neurontin (gabapentin): FDA approved for post-herpetic neuralgia, used off-label for fibromyalgia, diabetic neuropathy, and other neuropathic pain Lyrica (pregabalin): FDA approved for post-herpetic neuralgia, diabetic neuropathy, fibromyalgia, pain from spinal cord injury, and central neuropathic pain Tegretol (carbamazepine): FDA approved for trigeminal neuralgia, used off-label for diabetic neuropathy and postherpetic neuralgia Trileptal (oxcarbazepine): Used off-label for trigeminal neuralgia and other neuropathic pain Depacon (valproate): Used off-label for diabetic neuropathy

Side Effects and Warnings

Risks and side effects vary by drug and can include drowsiness, dizziness, or suicidal thoughts.

Side effects that are common with anticonvulsants are:

FatigueNauseaDizzinessBlurred vision

These effects are generally tolerable and tend to taper off over a few weeks or months. Less common and more serious side effects may include:

Skin rashes Liver problems or failure Pancreas problems Low white blood cell count (leukopenia), putting you at risk of infection Low platelet count (thrombocytopenia), putting you at risk of excessive bleeding

Antidepressants

Antidepressants are believed to treat chronic pain by altering the nervous system activity of certain neurotransmitters (chemical messengers), receptors, and pathways involved in processing pain and mood.

Antidepressant categories used for neuropathy include:

Tricyclics (TCAs)Selective serotonin reuptake inhibitors (SSRIs)Serotonin-norepinephrine reuptake inhibitors (SNRIs)

As with anticonvulsants, you need to taper off of antidepressants rather than stopping them suddenly. Your healthcare provider can offer you guidance in the proper way to wean yourself off of these drugs.

Tricyclics

Tricyclic antidepressants work by increasing the amount of the neurotransmitters serotonin and norepinephrine available to your brain by slowing a recycling process called reuptake. They also block receptors for other neurotransmitters—including acetylcholine and histamine—which makes them unable to send signals via brain cells.

For some people, these drugs can improve the balance of neurotransmitters and improve the way the brain functions. This can have effects on both mood and pain.

Tricyclics used for treating nerve pain include:

Amitriptyline: Used off-label for diabetic neuropathy, postherpetic neuralgia, migraine, and fibromyalgia Aventyl/Pamelor (nortriptyline): Used off-label for postherpetic neuralgia and diabetic neuropathy Norpramin (desipramine): Used off-label for postherpetic neuralgia and diabetic neuropathy

Tricyclic Side Effects

While they vary by drug, general side effects of tricyclic antidepressants include:

Blurry visionConstipationDizzinessDry mouthFatigueIncreased heart rateUrine retentionTremorWeight gain

SSRIs

Selective serotonin reuptake inhibitors specifically slow the reuptake of serotonin, leaving more serotonin available for use. This is believed to help in neuropathy because serotonin plays a key role in pain signals.

SSRIs generally cause fewer unpleasant side effects than tricyclics. However, studies suggest they have relatively small effects on neuropathic pain, so they’re not used as often as tricyclics and SNRIs.

SSRIs that are sometimes used for nerve pain are:

Luvox (fluvoxamine): Used off-label for diabetic neuropathyProzac (fluoxetine): Used off-label for fibromyalgia and migraine

SSRI Side Effects

Side effects of SSRIs include:

Agitation/anxietyDiarrheaDizzinessDry mouthExhaustionHeadacheInsomniaNauseaReduced libido or inability to orgasmTremors

Check the packaging information that came with your prescription for the side effects of the specific drug you’re taking.

SNRIs

Serotonin-norepinephrine reuptake inhibitors slow the reuptake of both of these neurotransmitters. This class includes the only antidepressants to receive FDA approval for pain.

Cymbalta (duloxetine): FDA approved for fibromyalgia and diabetic neuropathy Savella (milnacipran): FDA approved for fibromyalgia Venlafaxine: Used off-label for fibromyalgia, diabetic neuropathy, and migraine

SNRI Side Effects

General side effects of SNRIs are:

ConstipationDizzinessDry mouthExcessive sweatingHeadacheInsomniaNauseaReduced libido or inability to orgasm

Because side effects are somewhat different for each drug, be sure you’re familiar with the full list of side effects for the one you’re prescribed.

Opioids

Opioids, also called opiates or narcotics, are powerful prescription painkillers. They’re also addictive and classified as controlled substances. Because of an epidemic of recreational opioid abuse and potentially deadly overdose, many healthcare providers limit the use of opioids and require pain contracts, pill counts, and other measures meant to prevent addiction and abuse.

Opioids work by blocking pain signals that the body sends to the brain, so the brain doesn’t receive the signals or perceive the pain. They’re commonly used for managing pain from severe injuries, cancer pain, and post-surgical pain.

When it comes to neuropathic pain, opioids are generally considered a last line of treatment and prescribed only when all adjuvant painkillers fail.

Opioids include:

Codeine Ultram (tramadol) Morphine Vicodin (hydrocodone-acetaminophen) Percocet (oxycodone-acetaminophen) OxyContin (oxycodone) Methadone Opana (oxymorphone) Fentanyl

Side Effects and Warnings

Opioids are addictive. You should take the lowest effective dose for the shortest possible amount of time. The use of opioids for treating chronic pain is controversial.

Common side effects of drugs in this class include:

ConfusionConstipationDizzinessEuphoriaNausea and vomitingSleepiness

Over time, you can build up a tolerance to opioids, meaning you’ll need more of the drug to achieve the same level of pain control. This can put you at risk of addiction and fatal overdose.

Loss of consciousnessExtremely small pupilsSlow and shallow breathingChoking or gurgling soundsGoing limpSkin that’s pale, blue, or cold

Call 911 immediately if you suspect someone is having an opioid overdose.

Acetaminophen

Different from other painkillers, acetaminophen (the drug in Tylenol) works by increasing your pain threshold, which is the point at which a sensation registers as painful. Acetaminophen is commonly used alongside other pain relievers because it doesn’t interact negatively with them. That makes it a common go-to for breakthrough pain (pain that persists despite treatment).

Side Effects and Warnings

Some opioids, including Vicodin and Percocet, are combination drugs, meaning the narcotic medication is combined with acetaminophen. Many OTC drug formulations contain acetaminophen as well, including a lot of cold and flu remedies. Taking too much acetaminophen can lead to liver toxicity, which can be fatal.

If you take a combination opioid, check the labels of everything else you take to make sure you don’t get too much acetaminophen. When increasing your dosage, talk to your healthcare provider about whether a combination drug is still the best option for you.

Acetaminophen generally causes minimal side effects.

The most common ones are:

NauseaVomitingHeadache

NSAIDs

Non-steroidal anti-inflammatory drugs are not very effective at treating neuropathic pain unless inflammation is contributing to symptoms. These common painkillers are available OTC and by prescription, and they’re a common add-on to other drugs for treating breakthrough pain from neuropathy.

Common OTC NSAIDs include:

Advil/Motrin (ibuprofen) Aleve (naproxen) Aspirin (acetylsalicylic acid)

Both ibuprofen and naproxen are also available in prescription strengths.

Some NSAIDs that are only available by prescription are:

Celebrex (celecoxib) Indocin (indomethacin) Lodine (etodolac) Mobic (meloxicam) Orudis (ketoprofen) Relafen (nabumetone) Toradol (ketorolac) Voltaren (diclofenac)

Side Effects and Warnings

NSAIDs can be hard on your liver, kidneys, and stomach/intestines. Your healthcare provider may monitor for these problems if you’re on an NSAID long-term.

Common side effects of NSAIDs are:

Stomach painConstipationDiarrheaGasHeartburnNauseaVomitingDizziness

Less common side effects, which warrant immediate medical attention, include:

Heart attackStrokeHigh blood pressureHeart failure related to fluid retentionKidney problems, including failureLiver problems, including failureBleeding intestinal and stomach ulcersAnemia (low red blood cells)Skin reactions, which can be life-threateningAllergic reactions, which can be life-threateningAsthma attacks (only in people with pre-existing asthma)

Topical Analgesics

Some people with neuropathic pain find relief with topical pain medications, which are applied to the skin in the form of creams, gels, and patches and come OTC or by prescription. A real benefit of topical analgesics is that they work directly on the site of your pain and can be safely combined with other medications.

Topical medications are absorbed through your skin and enter the bloodstream. However, they’re often associated with a lower risk of side effects because they’re absorbed in smaller amounts that what you’d take in pill form and they don’t travel through your digestive system, where some painkillers can cause damage.

Different types of local analgesics work in different ways, and some are better than others for treating nerve pain.

Local anesthetics: These temporarily numb the nerves so they no longer send pain signals, and they work well for many people with neuropathic pain. Examples include lidocaine, benzocaine, tetracaine, and bupivanor. Counter-irritants: These cause new sensations that briefly distract your nerves from sending pain signals, and they are often good at reducing neuropathic pain. Sensations may be cold, hot, or tingling. Examples are capsaicin and methyl salicylate. Topical NSAIDs: These reduce inflammation when absorbed through the skin and are less likely to work for nerve pain unless it is due to inflammation. Example: diclofenac. Menthol products: These cause a cooling sensation that temporarily desensitizes your nerve endings and decreases blood flow (like an ice pack would), which may work better for inflammation-related pain than nerve pain. Look for menthol on the label.

Many topical products combine two or more of these ingredients. For example, Icy Hot contains both methyl salicylate and menthol, while Icy Hot with Lidocaine contains lidocaine and menthol.

Lidocaine

Lidocaine is one of the more commonly used topicals. It’s available both OTC and by prescription and in creams, patches, and other forms. Lidocaine is FDA approved for postherpetic neuralgia and peripheral nerve block anesthesia and epidural anesthesia. It’s used off-label for diabetic neuropathy.

Lidocaine is available OTC in some Icy Hot and Aspercreme products and by prescription in multiple forms, including patches and films, gels and jellies, lotions, creams, and ointments.

Some lidocaine-containing products are:

Lidoderm PatchAnastia Topical LotionMentho-Caine/Solupak Topical Ointment

The most common side effects of lidocaine include:

Red spots on the skin (petechiae)ItchingNauseaVomitingDizzinessAgitation

Capsaicin

Capsaicin, a popular OTC pain reliever, is FDA-approved for postherpetic neuralgia and diabetic neuropathy of the feet. It’s available in multiple products and forms, including creams, lotions, and a film. Capsaicin-containing products include:

Capzasin-P Topical CreamZostrix Topical CreamCastiva Warming Topical LotionQutenza Topical Film

Common capsaicin side effects include:

RashItchingNauseaInfectionVomitingHeadacheDry mouthCoughThroat irritationDizziness

The burning sensation that makes capsaicin work may be too intense for some people to tolerate.

Menthol

You can find menthol in a wide variety of topical products including:

Icy Hot Tiger Balm Biofreeze Bengay Aspercreme Heat

Menthol is available as a cream, gel, liquid, powder, spray, foam, film, and pad. Side effects are uncommon with menthol. If you get it in your eyes, be sure to thoroughly rinse it out.

Stop using the product and get medical attention if you experience:

Severe burning, stinging, redness, or irritationPain, swelling, or blistering where it was appliedHives, difficulty breathing, or swelling of your face, lips, tongue, or throat

To avoid burns, don’t use menthol products with a heating pad.

A Word From Verywell

It’s common to end up taking more than one medication to treat nerve pain, and that can potentially lead to harmful drug interactions. Be sure to check with your healthcare provider and pharmacist before adding any over-the-counter drugs, supplements, or herbal products to your treatment regimen. It’s also a good idea to have your pharmacist review your medications anytime you’re prescribed something new.

Most people with neuropathic pain require help from a healthcare provider or medical team to make significant improvements. Involve your healthcare provider in any self-treatment decisions and lifestyle modifications.

AmitriptylineCymbaltaDepaconGabapentinLyricaProzacTegretolVenlafaxine

However, opioids also come with negative side effects and a high risk of addiction. They are considered the last line of treatment for neuropathic pain and should only be used for short time periods. Long-term opioid use leads to physical dependence. Stopping opioids abruptly can lead to painful withdrawal symptoms and sickness.