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Inflammation-induced changes in rostral ventromedial medulla mu and kappa opioid receptor mediated antinociception.

Abstract
Acute microinjection of mu-, delta-, or kappa-opioid receptor (MOPr, DOPr, KOPr) agonists into the rostral ventromedial medulla (RVM) produces antinociception. Thermal antinociception produced by MOPr and DOPr agonists is potentiated during inflammation [Hurley RW, Hammond DL. The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 2000;20:1249-59]. Whether this potentiation extends to other stimulus modalities or to KOPr agonists is unknown. To examine these issues, rats received a unilateral intraplantar injection of complete Freund's adjuvant (CFA). Antinociception produced by RVM infusion of the KOPr agonist, U69593, and the MOPr agonist, DAMGO, was tested 4h-2 weeks thereafter. Thermal paw withdrawal latencies (PWLs) were assessed using the Hargreaves method. Mechanical thresholds were determined with the Von Frey and Randall-Selitto method. PWLs of the inflamed paw were reduced 4h-2 weeks after CFA injection. Infusion of either U69593 or DAMGO increased PWLs in CFA treated rats. A bilateral enhancement of the response to both agonists was observed 2 weeks relative to 4h post-CFA injection. Mechanical thresholds of the inflamed paw were decreased for >2 weeks post-CFA injection. Infusion of either agonist elevated thresholds of the inflamed and non-inflamed paws of CFA-treated rats. The magnitude of these effects was greater 2 weeks post-CFA injection for DAMGO and increased progressively for U69593. These data demonstrate that RVM infusion of MOPr or KOPr agonists attenuates CFA-evoked thermal and tactile allodynia and that these effects increase during prolonged inflammation. The augmented response of the non-inflamed paw to agonists suggests that inflammation induces centrally-mediated neuroplastic changes which enhance MOPr- and KOPr-mediated antinociception.
AuthorsRaf Jan-Filip Schepers, Janet Lynn Mahoney, Toni Shaun Shippenberg
JournalPain (Pain) Vol. 136 Issue 3 Pg. 320-330 (Jun 2008) ISSN: 1872-6623 [Electronic] United States
PMID17764840 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
Topics
  • Animals
  • Encephalitis (immunology)
  • Hyperalgesia (immunology)
  • Male
  • Medulla Oblongata (immunology)
  • Pain (immunology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa (immunology)
  • Receptors, Opioid, mu (immunology)
  • Touch (immunology)

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