Inflammation-induced changes in rostral ventromedial medulla mu and kappa opioid receptor mediated antinociception.
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.
Schepers
Raf Jan-Filip
RJ
University of Maryland School of Medicine, 660 W. Redwood Street, Baltimore, MD 21201, USA Integrative Neuroscience Section, Behavioral Neurosciences Branch, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, 333 Cassell Drive, Baltimore, MD 21224, USA.
Mahoney
Janet Lynn
JL
Shippenberg
Toni Shaun
TS
D000818:Animals; D004660:Encephalitis / Q000276:immunology*; D006930:Hyperalgesia / Q000276:immunology*; D008297:Male; D008526:Medulla Oblongata / Q000276:immunology*; D010146:Pain / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000276:immunology*; D017450:Receptors, Opioid, mu / Q000276:immunology*; D014110:Touch / Q000276:immunology
D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu