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.