title: Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.
abstract: There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region.
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Teodoro
authors.forename: Marcos F
authors.initials: MF
authors.lastname: Tronco Júnior
authors.forename: Aleksander R
authors.initials: AR
authors.lastname: Zampronio
authors.forename: Alessandra C
authors.initials: AC
authors.lastname: Martini
authors.forename: Giles A
authors.initials: GA
authors.lastname: Rae
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Chichorro
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D003251:Constriction, Pathologic / Q000473:pathology; D005157:Facial Pain / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D006120:Grooming / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007267:Injections; D008046:Lip; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C526005:SR140333B; D014326:Tropanes; D013373:Substance P