Ketamine in Chronic Pain: A Review

Summary & key facts

This review says that low (sub-anesthetic) doses of ketamine can produce strong short-term pain relief by blocking NMDA receptors and by boosting descending pain-inhibiting pathways. It is well documented to help with pain around the time of surgery and is linked to less long-term postoperative pain and lower opioid use. There is some evidence of longer-term benefit and of an antidepressant effect that could help people with chronic pain, but the number of clinical studies is still limited. Important side effects—especially psychomimetic (hallucination-like) effects—can affect whether people keep using it, and more research is needed on long-term safety and clear risk-versus-benefit answers.

Key facts:

• Sub-anesthetic doses of ketamine produce a potent analgesic effect by non-competitively blocking NMDA receptors and by enhancing descending inhibitory pathways.
• Ketamine’s short-term analgesic effect is well documented perioperatively and has been associated with reduced postoperative chronic pain and lower opioid consumption.
• The review notes that evidence for long-term benefits exists but that the number of clinical studies on long-term effects is still limited.
• Ketamine also has an antidepressant action at sub-anesthetic doses, which the authors say might be useful for people with chronic pain who also have depressive symptoms.
• Psychomimetic side effects (for example, hallucination-like experiences) are among the most relevant adverse effects and can reduce treatment adherence.
• Co-administration with benzodiazepines or α2-agonists is reported to facilitate clinical use of ketamine by reducing some side effects.
• Pharmacokinetic numbers reported: peak plasma time is about 1 minute after IV, 5–15 minutes after IM, and ~30 minutes after oral dosing; IV/IM bioavailability is ~93% and oral bioavailability is ~10–30%.
• Chemical and pharmacologic details: the S(+) enantiomer has about twice the analgesic and anesthetic potency of the racemic mixture; the active metabolite nor-ketamine has about 20–30% of ketamine’s potency.

Abstract

Ketamine has been used in the treatment of several pain syndromes, particularly those with a relevant neuropathic component. Sub-anesthetic doses of ketamine produce a potent analgesic effect, due to its inhibition of N-methyl-D-aspartate receptors and enhancement of descending inhibitory pathways. Its short-term analgesic effect is well-documented perioperatively, with an associated reduction in postoperative chronic pain and opioid consumption. Despite some evidence regarding its long-term benefits, the number of clinical studies is still limited. In addition to its analgesic effects, ketamine also possesses an anti-depressive action, which might be useful in the treatment of chronic pain patients. Several side effects have been described, the psychomimetic ones being the most relevant due to their impact on treatment adhesion. At present, co-administration of ketamine and benzodiazepines or α2-agonists facilitates its clinical application. Despite current evidence and increasing use, further investigation is still needed regarding its long-term safety profile and clearer risk-benefit analysis.

Topics

Anesthesia and Pain Management Pain Mechanisms and Treatments Treatment of Major Depression

Categories

Health Sciences Medicine Pharmacology

Tags

Analgesic Anesthesia Anesthetic Chronic pain Drug Intensive care medicine Internal medicine Ketamine Medicine Neuropathic pain Opioid Pharmacology Psychiatry Receptor