Ketamine analgesia produces intense analgesia at sub anesthetic doses and prompt induction of anesthesia when administered IV at higher doses.
Ketamine analgesia has an analgesic action at many sites both centrally and peripherally. These actions are mediated via multiple receptor subtypes, including opioid, NMDA, kainate, and GABAA receptors. Ketamine also inhibits serotonin and dopamine reuptake.
Intense analgesia can be achieved with sub anesthetic doses of ketamine, 0.15 to 0.5 mg/kg IV. Norketamine has significant analgesic properties which may explain the analgesic property of oral ketamine even after low plasma concentration due to high hepatic first-pass metabolism. S(+)-ketamine has a fourfold higher affinity for NMDA receptors than its R(-)-isomer and the analgesic potency of S(+)-ketamine is about twice that of racemic ketamine.
Evidence for the efficacy of ketamine analgesia for management of chronic pain is moderate to weak and ketamine analgesia has been used when first and second line of drugs failed. Ketamine has been used in conditions like fibromyalgia, orofacial pain, phantom limb pain, complex regional pain syndromes with variable success.
It has also been tried in chronic ischemic pain due to lower extremity arteriosclerosis obliterans. A synergistic effect between ketamine and opioids has been observed in cancer pain patients who have lost an analgesic response to high doses of morphine.
The N-methyl-D-aspartic acid (NMDA) receptors are involved in the control of post-herpetic neuralgia including allodynia and wind-up-like pain, i.e., pain evoked by repeatedly pricking the affected skin area.
Therefore, pain evoked by non-noxious stimulation of the skin (allodynia) and windup-like pain is inhibited by ketamine in sub anesthetic doses (0.15 mg/kg). Ketamine analgesia alleviates NMDA-related neuropathic pain. A variable response has been found with oral ketamine analgesia for the treatment of chronic neuropathic pain but the presence of side effects has limited its use.