Ketamine in Chronic Pain Management: An Evidence-Based Review

Abstract

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.

Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine

“…However, as only one concentration of ketamine was employed, only a single dose was administered, and effects of ketamine were assessed at only one time point, further controlled studies are needed to determine whether the therapeutic effects of ketamine in CRPS are limited to dynamic allodynia and punctate hyperalgesia or also include other forms of hyperalgesia. Parenteral and oral forms of ketamine have shown some promise for treating the burning pain and exquisite skin hypersensitivity of CRPS and other chronic pain states associated with nerve injury [42]. However, administration by these routes is limited by central side effects such as hallucinations and nightmares.…”

Neuropathic Pain Management in Chronic Laminitis

“…131,132 At subanesthetic doses (100-150 µg/kg as initial bolus followed by a CRI of 60-120 µg•kg -1 •hr -1 ) it blocks NMDA receptors, thereby modulating central sensitization induced both by tissue damage. [133][134][135][136][137] Ketamine exhibits synergism with classical analgesics such as opioids, NSAIDs, local anesthetics and α 2 agonists; therefore it reduces opioid analgesic consumption and increases analgesic quality. [135][136][137] Ketamine is used primarily as an antihyperalgesic and anti-allodynic compound in human patients at risk of developing maladaptive pain after major tissue damage and not primarily as an analgesic agent per se.…”

Postherpetic Neuralgia: From Preclinical Models to the Clinic

“…55,75,76 Human studies have demonstrated the potential of the NMDA antagonist ketamine in the treatment of various chronic pain conditions, although with significant adverse effects. 77 Local spinal application of an NMDA receptor antagonist attenuated VZV-induced behavioral sensitization. 41 In PHN patient trials, however, some oral NMDA receptor antagonists have not proved beneficial.…”