title: Contribution and interaction of kinin receptors and dynorphin A in a model of trigeminal neuropathic pain in mice.
abstract: Infraorbital nerve constriction (CION) causes hypersensitivity to facial mechanical, heat and cold stimulation in rats and mice and is a reliable model to study trigeminal neuropathic pain. In this model there is evidence that mechanisms operated by kinin B1 and B2 receptors contribute to heat hyperalgesia in both rats and mice. Herein we further explored this issue and assessed the role of kinin receptors in mechanical hyperalgesia after CION. Swiss and C57Bl/6 mice that underwent CION or sham surgery or dynorphin A (1-17) administration were repeatedly submitted to application of either heat stimuli to the snout or mechanical stimuli to the forehead. Treatment of the animals on the fifth day after CION surgery with DALBK (B1 receptor antagonist) or HOE-140 (B2 receptor antagonist), both at 0.01-1μmol/kg (i.p.), effectively reduced CION-induced mechanical hyperalgesia. Knockout mice for kinin B1, B2 or B1/B2 receptors did not develop heat or mechanical hyperalgesia in response to CION. Subarachnoid dynorphin A (1-17) delivery (15nmol/5μL) also resulted in orofacial heat hyperalgesia, which was attenuated by post-treatment with DALBK (1 and 3μmol/kg, i.p.), but was not affected by HOE-140. Additionally, treatment with an anti-dynorphin A antiserum (200μg/5μL, s.a.) reduced CION-induced heat hyperalgesia for up to 2h. These results suggest that both kinin B1 and B2 receptors are relevant in orofacial sensory nociceptive changes induced by CION. Furthermore, they also indicate that dynorphin A could stimulate kinin receptors and this effect seems to contribute to the maintenance of trigeminal neuropathic pain.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, SC, Brazil. Electronic address: a.luiz@ucl.ac.uk.
authors.forename: A P
authors.initials: AP
authors.lastname: Luiz
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: S D
authors.initials: SD
authors.lastname: Schroeder
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: G A
authors.initials: GA
authors.lastname: Rae
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, SC, Brazil; Center of Innovation and Pre-clinical Trials, Florianopolis, SC, Brazil.
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: J G
authors.initials: JG
authors.lastname: Chichorro
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D004399:Dynorphins / Q000378:metabolism* / Q000494:pharmacology; D005157:Facial Pain / Q000378:metabolism*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010147:Pain Measurement; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism; D014110:Touch
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D018377:Neurotransmitter Agents; D018002:Receptors, Bradykinin; C051090:bradykinin, Leu(8)-des-Arg(9)-; D004399:Dynorphins; C065679:icatibant; D001920:Bradykinin
keywords: dynorphin A; kinin; orofacial hyperalgesia; trigeminal neuropathic pain