Neuropathic pains have often been classified as opioid resistant. Here, the ability of systemic (i.p.), intracerebroventricular (i.c.v.) and intrathecal (i.th.) morphine to inhibit mechanical allodynia were studied in a nerve ligation (L5, L6 nerve roots) model of neuropathic pain in rats. Morphine administered i.p. or i.c.v. produced dose-dependent antiallodynia which was readily antagonized by naloxone (5 mg kg-1, i.p. at -10 min). In contrast, i.th. morphine at doses up to 100 micrograms was without effect. These data suggest that the failure of i.th. morphine to produce antiallodynic effects may be due, in part, to the lack of available functional spinal opioid mu-receptors which may occur following nerve injury. In contrast, the antiallodynic actions of i.p. or i.c.v. morphine appear to depend on supraspinal activation of opioid (mu?) receptors and subsequent activation of descending modulatory systems. The inconsistent data seen clinically with morphine in neuropathic pains may be related to the lack of supraspinal/spinal synergy that is normally associated with morphine efficacy in conditions of acute pain.