QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.060582v1 309/1/380    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rashid, M. H. Articles by Ueda, H. Search for Related Content PubMed PubMed Citation Articles by Rashid, M. H. Articles by Ueda, H.

NEUROPHARMACOLOGY

Loss of Peripheral Morphine Analgesia Contributes to the Reduced Effectiveness of Systemic Morphine in Neuropathic Pain

Divisions of Molecular Pharmacology and Neuroscience (M.H.R., M.I., H.U.) and Integrative Sensory Physiology (K.T.), Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

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.

Address correspondence to: Dr. Hiroshi Ueda, Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521. E-mail: ueda{at}net.nagasaki-u.ac.jp

This article has been cited by other articles:

				Y.-P. Chen, S.-R. Chen, and H.-L. Pan Effect of Morphine on Deep Dorsal Horn Projection Neurons Depends on Spinal GABAergic and Glycinergic Tone: Implications for Reduced Opioid Effect in Neuropathic Pain J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 696 - 703. [Abstract] [Full Text] [PDF]