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.