Ketamine for Chronic Pain

Ketamine is well known for decades to relieve acute pain in the emergency room, operating room, on the battlefield and in the burn unit.  Now, scientists are explaining how it helps with chronic neuropathic pain. Neuropathic pain is essentially pain that arises from a direct involvement of the nerve.  Conditions include chronic regional pain syndrome (CRPS)/reflex sympathetic dystrophy (RDS), trigeminal and occipital neuralgia, fibromyalgia, and phantom limb pain, among other conditions.  Patients often start with oral medications to treat the pain, including antidepressants, gabapentin, or pregabalin. They add in therapies like sympathetic nerve blocks, psychotherapy, physical therapy, and nerve stimulators. These are often accompanied by opioids, which are potent analgesics, but not a preferred choice for neuropathic pain.  Patients may get stuck in the cycle of increased dosing of opioids, leading to dependence, possible addiction, and even hyperalgesia. Hyperalgesia occurs when chronic or heavy opioid use actually causes more pain from a stimulus, perpetuating the likelihood of increasing the opioid dose again.

Ketamine therapy for neuropathic pain targets N-methyl-D-aspartate (NMDA) receptors, the same key receptor for relief of depression and other mood disorders.  Pain fibers release glutamate which activates this receptor.  Activation opens a channel that increases ion flow into the cell, causing a cascade of events, including neurotoxicity. This receptor is also known to contribute to “wind up phenomenon”, central sensitization, and chronic pain.(1) Wind up phenomenon is the worsening of pain by repeated pain stimuli.  Central sensitization is the increased excitability of neurons in the spinal cord contributing to hyperalgesia, or heightened sensitivity to pain.

Outpatient IV ketamine infusions do help a significant number of people that have failed other options. A 5 year retrospective analysis done by Sheetal Patil, MD showed lasting pain relief in up to half the patients for as long as 3 weeks.  The ketamine treatments included a series of 30 minute infusions in the study setting.  Dr. Patil also notes ketamine has been shown to decrease opioid tolerance.(2)   Other studies show a higher response rate, but these involve inpatient ketamine infusions of a higher dose and continuous over 2 or more days.(3)             

As an outpatient, ketamine infusions may run from 40 minutes up to 4 hours, depending on the pain condition.  These infusions are repeated as a series of injections.  The number depends on the ketamine clinic.  Patients may then return for additional boosters, or treatments to extend their pain relief.  Ketamine is not a cure, rather a treatment for this debilitating disease.  It can reduce dependence on opioids, improve sleep, and improve quality of life for patients that have failed other options. Research is ongoing to further explain the intricacies of ketamine and how it may further benefit chronic pain patients.

  1. Shanthanna H, “Intravenous Therapies in the Management of Neuropathic Pain: A Review on the Use of Ketamine and Lidocaine in Chronic Pain Management,”
  2. Patil S, Anitescu M, “Efficacy of Outpatient Ketamine Infusions in Refractory Chronic Pain Syndromes: A 5-Year Retrospective Analysis,” Pain Medicine, Volume 13, Issue 2, 1 February 2012, Pages 263-269.
  3. Correll G E, Maleki J, et al, ”Subanesthetic Ketamine Infusion Therapy: A Retrospective Analysis of a Novel Therapeutic Approach to Complex Regional Pain Syndrome,” Pain Medicine, Volume 5, Number 3, 2004, Pages 263-275.

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