title: Role of TRPV1 channels of the dorsal periaqueductal gray in the modulation of nociception and open elevated plus maze-induced antinociception in mice.
abstract: Recent findings have identified the presence of transient receptor potential vanilloid-1 (TRPV1) channels within the dorsal portion of the periaqueductal gray (dPAG), suggesting their involvement in the control of pain and environmentally-induced antinociception. Environmentally, antinociception may be achieved through the use of an open elevated plus maze (oEPM, an EPM with 4 open arms), a highly aversive environmental situation. Here, we investigated the role of these TRPV1 channels within the dPAG in the modulation of a tonic pain and in the oEPM-induced antinociception. Male Swiss mice, under the nociceptive effect of 2.5% formalin injected into the right hind paw, received intra-dPAG injections of the TRPV1 agonist (capsaicin: 0, 0.01, 0.1 or 1.0 nmol/0.2 μL; Experiment 1) or antagonist (capsazepine: 0, 10 or 30 nmol/0.2 μL; Experiment 2) or combined injections of capsazepine (30 nmol) and capsaicin (1.0 nmol) (Experiment 3) and the time spent licking the formalin-injected paw was recorded. In Experiment 4, mice received intra-dPAG capsazepine (0 or 30 nmol) and were exposed to the oEPM or to a control situation, an enclosed EPM (eEPM; an EPM with 4 enclosed arms). Results showed that while capsaicin (1 nmol) decreased the time spent licking the formalin-injected paw, capsazepine did not change nociceptive response. Capsazepine (30 nmol) blocked pain inhibition induced by capsaicin and mildly attenuated the oEPM-induced antinociception. Our results revealed an important role of TRPV1 channels within the dPAG in the modulation of pain and in the phenomenon known as fear-induced antinociception in mice.
authors.affiliation: Joint Graduate Program in Physiological Sciences, UFSCar/UNESP-São Carlos, SP, 13565-905, Brazil; School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, 14801-902, Araraquara, SP, Brazil.
authors.forename: Diego Cardozo
authors.initials: DC
authors.lastname: Mascarenhas
authors.affiliation: School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, 14801-902, Araraquara, SP, Brazil.
authors.forename: Karina Santos
authors.initials: KS
authors.lastname: Gomes
authors.affiliation: Joint Graduate Program in Physiological Sciences, UFSCar/UNESP-São Carlos, SP, 13565-905, Brazil; School of Pharmaceutical Sciences, Universidade Estadual Paulista-UNESP, 14801-902, Araraquara, SP, Brazil. Electronic address: souzarn@fcfar.unesp.br.
authors.forename: Ricardo Luiz
authors.initials: RL
authors.lastname: Nunes-de-Souza
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005239:Fear / Q000502:physiology; D008297:Male; D018782:Maze Learning; D051379:Mice; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000523:psychology*; D010147:Pain Measurement; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C071423:capsazepine; D002211:Capsaicin
keywords: Antinociception; Formalin test; Mice; Open elevated plus maze; Periaqueductal gray matter; TRPV1