[Suppressive effects of ketamine on neuropathic pain].
We previously reported that ketamine analgesia in acute pain was produced by the activation of the monoaminergic descending inhibitory system. Recent studies have confirmed that the NMDA receptor antagonists attenuate the hyperalgesia in neuropathic pain. In this study, we investigated the suppressive effects of a clinically available NMDA antagonist, ketamine, and the mechanisms of its effects on neuropathic pain in rats with peripheral mononeuropathy. A unilateral chronic constriction injury (CCI) model was introduced by loose ligation of the sciatic nerve of the rats. The CCI rats showed hyperalgesia to thermal and mechanical pressure stimuli on the injured side of their hind paws. Intraperitoneal (IP) ketamine (25 or 50 mg.kg-1) and intrathecal (IT) ketamine (25-500 micrograms) reversed, dose-dependently, both thermal and mechanical hyperalgesia. Pretreatment with IT yohimbine (alpha-2 adrenergic antagonist) or IT methysergide (serotonergic antagonist) did not show the suppressive effects of IP ketamine (50 mg.kg-1) on hyperalgesia. Concentrations of norepinephrine (NE) and serotonin (5HT) in the spinal dorsal horn were measured using high performance liquid chromatography. The CCI rats showed increased NE and 5HT concentrations on both ligated and unligated sides of spinal dorsal horn, compared with shamoperated rats. IP ketamine (50 mg.kg-1) in the CCI rats did not boost the spinal NE or 5HT levels. These results indicate that the anti-hyperalgesic effect of ketamine is derived from a direct action on the spinal cord, but not from the activation of monoaminergic descending inhibitory systems.
Sonoda
H
H
Department of Anesthesiology, Sapporo Medical University School of Medicine.
Omote
K
K
D000208:Acute Disease; D000778:Anesthetics, Dissociative / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007649:Ketamine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012584:Sciatic Nerve / Q000293:injuries*
D000778:Anesthetics, Dissociative; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine