BACKGROUND: Although the efficacy of morphine in a neuropathic pain state is somewhat controversial, intrathecally administered morphine reversed the mechanical allodynia in a previous animal study. Using a behavioral test, we investigated the mechanism of the antiallodynic action of intrathecal morphine by administering opioids, alpha2 adrenergic and cholinergic receptor antagonists in a rat model of neuropathic pain induced by a spinal nerve ligation injury. METHODS: Male Sprague Dawley rats were prepared with a tight ligation of the left lumbar 5th and 6th spinal nerves and insertion of a chronic lumbar intrathecal catheter. Morphine 1 microgram was administered intrathecally to attenuate the mechanical allodynia. Naloxone 10 microgram, yohimbine 30 microgram, prazosin 30 microgram, atropine 10 microgram, pirenzepine 10 microgram, and methoctramine 10 microgram was administered intrathecally before and after the injection of morphine in order to investigate the reversal of an increased allodynic threshold by morphine. The allodynic thresholds for the left hindpaw withdrawal to von Frey hairs were assessed and converted to %MPE. RESULTS: A reduction of mechanical allodynia by intrathecal morphine was produced. Naloxone pretreatment, but not posttreatment, reversed the antiallodynic effect of intrathecal morphine (P < 0.01). All alpha2 adrenergic and cholinergic receptor antagonists used here did not reverse it. CONCLUSIONS: The results suggest that the reversal mechanism of mechanical allodynia by intrathecal morphine appears to be mediated mostly by the opioid receptor system, but not the alpha2 adrenergic and cholinergic receptor systems, at the spinal level in a rat model of a spinal nerve ligation injury.