Spinal and Peripheral Mechanisms Involved in the Enhancement of Morphine Analgesia in Acutely Inflamed Mice
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The analgesic effect induced by opiates is often potentiated during experimental inflammatory processes. We describe here that lower doses of systemic morphine are necessary to increase thermal withdrawal latencies measured in both hind paws of mice acutely inflamed with carrageenan than in healthy ones. This bilateral potentiation seems mediated through spinal opioid receptors since it is inhibited by the intrathecal (i.t.), but not intraplantar (i.pl.) administration of the opioid receptor antagonist naloxone-methiodide, and also appears when morphine is i.t. administered. Furthermore, the i.pl. administration of the nitric oxide (NO) synthase inhibitor, l-NMMA, or the K ATP + -channel blocker, glibenclamide, to carrageenan-inflamed mice inhibits the enhanced effect of systemic morphine in the paw that receives the injection of the drug, without affecting the potentiation observed in the contralateral one. The i.pl. administration of l-NMMA also partially antagonised the analgesic effect induced by i.t. morphine in inflamed mice. Finally, the increased analgesic effect evoked by the i.pl. administration of the NO donor SIN-1 either in the inflamed or in the contralateral paw of carrageenan-inflamed mice suggests that enhanced responsiveness to the peripheral analgesic effect of NO may be also underlying the bilateral potentiation of morphine-induced analgesia in acutely inflamed mice.
KeywordsMorphine Thermal hyperalgesia Carrageenan-induced inflammation Nitric oxide Mice
Grants were provided by MEC-FEDER (SAF2006-05226). The Instituto Universitario de Oncología is supported by Obra Social Cajastur-Asturias, Spain.
- Sykes KT, White SR, Hurley RW, Mizoguchi H, Tseng LF, Hammond DL (2007) Mechanisms responsible for the enhanced antinociceptive effects of micro-opioid receptor agonists in the rostral ventromedial medulla of male rats with persistent inflammatory pain. J Pharmacol Exp Ther 322:813–821CrossRefPubMedGoogle Scholar
- Whiteside GT, Boulet JM, Walker K (2005) The role of central and peripheral mu opioid receptors in inflammatory pain and edema: a study using morphine and DiPOA ([8-(3, 3-diphenyl-propyl)-4-oxo-1-phenyl-1, 3, 8-triaza-spiro[4.5]dec-3-yl]-acetic acid). J Pharmacol Exp Ther 314:1234–1240CrossRefPubMedGoogle Scholar