title: Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice.
abstract: Postoperative pain management is a clinical challenge that can be complicated by opioid-induced hyperalgesia (OIH). Kinin receptors could mediate both the acute and chronic phases of inflammation and pain. A few recent studies suggest that dynorphin A could maintain neuropathic pain by activating the bradykinin (BK) receptor. Thus, the effect of a single administration of sufentanil (a μ-opioid receptor agonist) was investigated in a model of carrageenan-induced inflammatory pain using three strains of mice, i.e., knockout mice for one kinin receptor, B1R or B2R (B1KO, B2KO), and wild-type C57/BL6J mice (WT) treated with either a B1R (R954) or a B2R antagonist (HOE140) or a KKS inhibitor (aprotinin). Pain was assessed and compared between the different groups using two behavioral tests exploring mechanical (von Frey filaments) and thermal (Hargreaves test) sensitivity. Pretreatment with sufentanil induced a sustained increase in pain sensitivity with a delayed return to baseline values characterizing an OIH in carrageenan-injected mice only. Sufentanil-induced OIH was not observed in B2KO but persisted in B1KO and was blunted by aprotinin and the B2R antagonist only. Collectively, our data indicate that the B2R receptor and BK synthesis or availability are essential peripheral steps in the mechanism leading to OIH in a pain context.
authors: Universite de Toulouse, Universite Paul Sabatier, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France.
authors: Sébastien
authors: S
authors: Grastilleur
authors: Lionel
authors: L
authors: Mouledous
authors: Jerome
authors: J
authors: Bedel
authors: Jonathan
authors: J
authors: Etcheverry
authors: Michael
authors: M
authors: Bader
authors: Jean-Pierre
authors: JP
authors: Girolami
authors: Olivier
authors: O
authors: Fourcade
authors: Bernard
authors: B
authors: Frances
authors: Vincent
authors: V
authors: Minville
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000503:physiopathology*; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D017409:Sufentanil / Q000009:adverse effects
chemical_list: D000701:Analgesics, Opioid; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D017409:Sufentanil