Peripheral opioid receptors mediating antinociception in inflammation. Activation by endogenous opioids and role of the pituitary-adrenal axis.
This study investigated the involvement of endogenous opioid peptides in mediating cold water swim (CWS) stress-induced antinociception (SIA) in rats with unilateral hind paw inflammation induced by Freund's complete adjuvant (FCA). Following 0.5, 1 and 2 min of CWS, there was a duration-dependent elevation of paw pressure threshold (PPT) in both inflamed and non-inflamed paws which was maximal immediately after CWS and returned to control values within 15 min. The antinociception elicited in the inflamed paw was significantly greater than that elicited in the non-inflamed paw. The antinociception induced by a 1 min CWS was dose dependently antagonized by tertiary naloxone (0.125-1 mg/kg s.c.) and completely reversed by tertiary naltrexone (0.5 mg/kg). Quaternary naltrexone (5-40 mg/kg s.c.) was similarly effective in reversing the elevation of inflamed PPT induced by a 1 min CWS stress. In contrast, similar doses of quaternary naltrexone had no effect against centrally mediated morphine antinociception in non-inoculated rats. Adrenalectomy was without effect on the pattern of SIA seen in FCA-treated rats. Surgical hypophysectomy completely abolished the differential antinociception induced by 0.5 and 1 min durations of CWS but had little effect on that following 2 min of CWS stress. Inhibition of hypophysial corticotrophic cell secretion with dexamethasone (300 micrograms/kg) injected s.c. 120 min prior to CWS completely abolished the differential SIA at all durations of CWS tested. beta-Endorphin 12.5 micrograms/kg administered i.v. in non-stressed rats also caused a greater elevation of PPT in inflamed than in non-inflamed paws. This effect was not reversed by concomitant i.v. administration of (-) tertiary naloxone 5 mg/kg or quaternary naltrexone 20 mg/kg.
Parsons
Chris G
CG
Department of Neuropharmacology, Max Planck Institut für Psychiatrie, D-8033 Planegg-MartinsriedF.R.G. Department of Pharmacology, Institute of Physiological Sciences, Medical Academy of Warsaw, Krakowskie Przedmiescie 26/28, 00-927 Warsaw 64 Poland Department of Anesthesiology, Ludwig-Maximilians-Universität, Klinikum Grosshadern, D-8000 Munich 70 F.R.G.
Członkowski
Andrej
A
Stein
Christoph
C
Herz
Albert
A
D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000502:physiology*; D005528:Foot; D007016:Hypophysectomy; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009619:Nociceptors / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology; D013550:Swimming
D004723:Endorphins; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone