Neuropathic Pain

The short version

●Neuropathic pain is caused by damage or disease of the nervous system itself (not tissue injury) — described as burning, shooting, electric, or stabbing, often with numbness, tingling, or pain from light touch (allodynia).
●Common causes include diabetic neuropathy, post-herpetic neuralgia (after shingles), nerve injury, chemotherapy, and central conditions like MS or stroke.
●First-line medications are specific: certain antidepressants (duloxetine, amitriptyline) and gabapentinoids (gabapentin, pregabalin) — ordinary painkillers and opioids work poorly.
●Central sensitization, an over-amplified NMDA-mediated pain system, is central to many neuropathic pain states — the rationale for ketamine.
●Ketamine, an NMDA-receptor antagonist, has supportive evidence in refractory neuropathic pain and is included in professional consensus guidelines for IV ketamine in chronic pain.
●It is not first-line; it is for neuropathic pain that hasn't responded to standard agents, often alongside the depression chronic nerve pain commonly causes.

Clinical definition

Neuropathic pain arises from a lesion or disease of the somatosensory nervous system — distinct from nociceptive pain, which signals actual or threatened tissue damage. It is characterized by spontaneous burning, shooting, or electric-shock sensations and evoked abnormalities such as allodynia (pain from normally non-painful stimuli) and hyperalgesia, frequently with numbness, tingling, or other sensory changes in the affected distribution. Peripheral causes include diabetic polyneuropathy, post-herpetic neuralgia, nerve compression or injury, chemotherapy-induced neuropathy, and trigeminal neuralgia; central causes include spinal cord injury, multiple sclerosis, and post-stroke pain. Central sensitization — a state in which NMDA-receptor-mediated processes amplify and sustain pain signaling in the central nervous system — is a key mechanism in many neuropathic pain states, which explains both why ordinary analgesics underperform and why NMDA antagonists like ketamine are of interest.

How it differs from related conditions

vs. Nociceptive pain

Signals tissue damage (a sprain, arthritis) and responds to ordinary analgesics; neuropathic pain comes from the nervous system itself and needs different drugs.

vs. Chronic pain

Neuropathic pain is one mechanism within the broader chronic-pain umbrella, defined by its nervous-system origin and characteristic burning/electric quality.

vs. Complex regional pain syndrome

CRPS has neuropathic features but adds the autonomic, trophic, and motor limb changes that define it.

vs. Fibromyalgia

A central sensitization syndrome of widespread pain without a specific nerve lesion; neuropathic pain follows a nerve's distribution and has an identifiable cause.

First-line treatments

Antidepressants for pain (duloxetine, amitriptyline, nortriptyline)

First-line; SNRIs and tricyclics modulate descending pain pathways independent of their effect on mood.

Gabapentinoids (gabapentin, pregabalin)

First-line; calm overactive nerve signaling.

Topical agents (lidocaine, capsaicin)

Useful for localized neuropathic pain (e.g., post-herpetic neuralgia) with minimal systemic effects.

Treating the underlying cause

Glycemic control in diabetic neuropathy, decompression for nerve entrapment, and antiviral/early treatment for shingles all matter.

When standard treatments fail

When first-line antidepressants, gabapentinoids, and topicals fail, the steps are to confirm adequate trials and doses, combine agents with complementary mechanisms, treat the underlying cause more aggressively, and add interventional options (nerve blocks, neuromodulation, spinal cord stimulation) matched to the diagnosis. Opioids are de-emphasized given poor long-term benefit and harm. For refractory, centrally-sensitized neuropathic pain — and for the depression chronic nerve pain so often produces — NMDA-antagonist treatment with ketamine is supported by professional consensus as an option.

Where ketamine fits

Ketamine has a recognized, if second-line, role in neuropathic pain. As an NMDA-receptor antagonist it directly targets the central sensitization that sustains many neuropathic pain states, and multi-society consensus guidelines include refractory neuropathic pain among the conditions for which intravenous ketamine is supported (Cohen 2018); the foundational neuropathic-pain evidence base (Finnerup 2015) frames where standard agents help and fall short. As with all chronic pain, the benefit can be partial and sometimes temporary, ketamine does not repair the underlying nerve damage, and it works within a comprehensive plan. For Tovani, the dual angle matters: chronic neuropathic pain frequently drives a treatment-resistant depression, and ketamine can address both. It is considered for neuropathic pain that has failed adequate first-line treatment.

Where this fits with Tovani

Tovani treats neuropathic pain primarily when it is refractory to standard agents and/or co-occurs with treatment-resistant depression — a common pairing given how disabling persistent nerve pain is. Eligibility screening captures the pain diagnosis, prior treatments, and mood, and patients are encouraged to keep treating the underlying cause and first-line agents alongside ketamine. Patients with untried first-line options are generally directed to those first; ketamine is for the refractory end.

Check eligibility Find treatment options The science behind ketamine

Frequently asked

Why don't normal painkillers work for nerve pain?

Because neuropathic pain comes from the nervous system itself, not tissue damage. NSAIDs and even opioids, which target tissue-level pain, work poorly. The effective drugs are specific antidepressants (duloxetine, amitriptyline) and gabapentinoids (gabapentin, pregabalin) that calm overactive nerve signaling.

Is ketamine proven for neuropathic pain?

Ketamine has supportive evidence and is included in professional consensus guidelines for refractory chronic pain, including neuropathic pain, because it targets the central sensitization behind it. The benefit can be partial or temporary, it doesn't repair the nerve, and it's a second-line option used within a broader plan.

I have nerve pain and I'm depressed — is that connected?

Very often, yes. Persistent neuropathic pain frequently drives depression, and they share pathways. Treating both matters, and ketamine is one option that can address the treatment-resistant depression that chronic nerve pain causes.

Will ketamine cure my neuropathy?

No. Ketamine can reduce refractory neuropathic pain for some patients but does not repair the underlying nerve damage or cure the cause. It's used to reduce pain and the associated depression within a comprehensive plan that still treats the underlying condition.

References

Finnerup NB et al. 2015, The Lancet Neurology — Systematic review and meta-analysis establishing first-line pharmacotherapy for neuropathic pain (antidepressants, gabapentinoids) and the limits of other agents. (PMID 25575710)
Cohen SP et al. 2018, Regional Anesthesia and Pain Medicine — Consensus guidelines including refractory neuropathic pain among indications for intravenous ketamine. (PMID 29870458)
Murrough JW et al. 2013, American Journal of Psychiatry — Ketamine RCT in treatment-resistant depression, the comorbidity common in chronic neuropathic pain. (PMID 23982301)

Last reviewed by Dr. Ben Soffer, DO on May 31, 2026. This page is educational and not a substitute for clinical evaluation. A physician determines whether ketamine therapy is appropriate for your specific situation.