RT Journal Article
SR Electronic
T1 Loss of Peripheral Morphine Analgesia Contributes to the Reduced Effectiveness of Systemic Morphine in Neuropathic Pain
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 380
OP 387
DO 10.1124/jpet.103.060582
VO 309
IS 1
A1 Rashid, Md Harunor
A1 Inoue, Makoto
A1 Toda, Kazuo
A1 Ueda, Hiroshi
YR 2004
UL http://jpet.aspetjournals.org/content/309/1/380.abstract
AB It is well known that the analgesic potency of morphine is reduced in neuropathic pain. In this study, we demonstrate that the decreased effectiveness of systemic morphine in neuropathic pain might be caused by the loss of morphine analgesia at the periphery. When given s.c. or i.t., the dose-response curves for morphine analgesia in Hargreaves thermal test were shifted rightward in partial sciatic nerve-injured mice compared with control sham-operated mice. The dose-response curves for i.c.v. morphine analgesia, however, were unchanged in nerve-injured mice, indicating no decrease in morphine potency at the supraspinal level. On the other hand, the dose-dependent analgesia produced by intraplantar (i.pl.) morphine in sham-operated mice almost completely disappeared in nerve-injured mice. With the more sensitive algogenic-induced nociceptive flexion test, significant reduction in the analgesic potency of systemic morphine was observed for bradykinin (BK) nociception in nerve-injured mice, and the analgesic effect of i.pl. morphine against BK nociception in sham-operated mice disappeared in nerve-injured mice. In immunohistochemical experiments, we found that, under normal state, μ-opioid receptors (MOPs) were mainly expressed in small-diameter unmyelinated dorsal root ganglion (DRG) neurons and colocalized with bradykinin B2 receptors. When we examined MOP expression in the DRG of nerve-injured mice, we observed a drastic decrease in MOP expression. Altogether, these data suggest that the lower potency of systemic morphine in neuropathic pain could be at least partly caused by the decreased MOP expression in DRG and subsequent loss of peripheral morphine analgesia in such a condition. The American Society for Pharmacology and Experimental Therapeutics