title: Inflammation mobilizes local resources to control hyperalgesia: the role of endogenous opioid peptides.
abstract: The aim of the present study was to investigate the mechanisms underlying the endogenous control of nociception at a peripheral level during inflammation. Using a pharmacological approach and the rat paw pressure test, we assessed the effect of an intraplantar injection of naloxone, an opioid receptor antagonist, and bestatin, an aminopeptidase inhibitor, on hyperalgesia induced by carrageenan, which mimics an inflammatory process, or prostaglandin E(2) (PGE(2)), which directly sensitizes nociceptors. Naloxone induced a significant and dose-dependent (25, 50 or 100 μg) increase in carrageenan-induced hyperalgesia, but not PGE(2)-induced hyperalgesia. Bestatin (400 μg/paw) significantly counteracted carrageenan-induced hyperalgesia, inducing an increase in the nociceptive threshold compared to control, but it did not modify hyperalgesia induced by PGE(2) injection into the rat paw. Positive β-endorphin immunoreactivity was increased in paw inflammation induced by carrageenan in comparison with the control group. However, PGE(2) did not significantly alter the immunostained area. These results provide evidence for activation of the endogenous opioidergic system during inflammation and indicate that this system regulates hyperalgesia through a negative feedback mechanism, modulating it at a peripheral level.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil.
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Alves
authors.forename: Patrícia G
authors.initials: PG
authors.lastname: da Motta
authors.forename: Patrícia P
authors.initials: PP
authors.lastname: Lima
authors.forename: Celso M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Caliari
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Pacheco
authors.forename: Cinthia F
authors.initials: CF
authors.lastname: Pacheco
authors.forename: Janetti N
authors.initials: JN
authors.lastname: Francischi
authors.forename: Igor D G
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000009:adverse effects / Q000819:agonists / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced; D007249:Inflammation / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011480:Protease Inhibitors; D009270:Naloxone; D001615:beta-Endorphin; D002351:Carrageenan; D007930:Leucine; C012211:ubenimex; D015232:Dinoprostone