Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice

Detalhes bibliográficos
Autor(a) principal: Mascarenhas, Diego C. [UNESP]
Data de Publicação: 2017
Outros Autores: Gomes, Karina S. [UNESP], Sorregotti, Tatiani [UNESP], Nunes-de-Souza, Ricardo L. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3389/fphar.2017.00695
http://hdl.handle.net/11449/159854
Resumo: Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA) within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1) and Cannabinoid type 1 (CB1) receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG) of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist), capsaicin (TRPV1 agonist), WIN (CB1 agonist), AM251 (CB1 antagonist), and 6-iodonordihydrocapsaicin (6-IODO) (TRPV1 selective antagonist) and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB) substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1-and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.
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spelling Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Micevanilloid substratescannabinoid substratesanandamideperiaqueductal grayantinociceptionDivergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA) within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1) and Cannabinoid type 1 (CB1) receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG) of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist), capsaicin (TRPV1 agonist), WIN (CB1 agonist), AM251 (CB1 antagonist), and 6-iodonordihydrocapsaicin (6-IODO) (TRPV1 selective antagonist) and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB) substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1-and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)PADC/FCF/Ar-UNESPUniv Fed Sao Carlos, Joint Grad Program Physiol Sci, Sao Carlos, SP, BrazilSao Paulo State Univ, Sao Carlos, SP, BrazilSao Paulo State Univ, Sch Pharmaceut Sci, Lab Neuropsychopharmacol, Araraquara, SP, BrazilSao Paulo State Univ, Sao Carlos, SP, BrazilSao Paulo State Univ, Sch Pharmaceut Sci, Lab Neuropsychopharmacol, Araraquara, SP, BrazilCNPq: 478696/2013-2CNPq: 306556/2015-4FAPESP: 2013/01283-6FAPESP: 2013/06764-2FAPESP: 2013/03445-3Frontiers Media SaUniversidade Federal de São Carlos (UFSCar)Universidade Estadual Paulista (Unesp)Mascarenhas, Diego C. [UNESP]Gomes, Karina S. [UNESP]Sorregotti, Tatiani [UNESP]Nunes-de-Souza, Ricardo L. [UNESP]2018-11-26T15:45:29Z2018-11-26T15:45:29Z2017-10-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://dx.doi.org/10.3389/fphar.2017.00695Frontiers In Pharmacology. Lausanne: Frontiers Media Sa, v. 8, 11 p., 2017.1663-9812http://hdl.handle.net/11449/15985410.3389/fphar.2017.00695WOS:000412243800001WOS000412243800001.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers In Pharmacology1,587info:eu-repo/semantics/openAccess2023-10-26T06:12:40Zoai:repositorio.unesp.br:11449/159854Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:03:38.978649Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
title Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
spellingShingle Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
Mascarenhas, Diego C. [UNESP]
vanilloid substrates
cannabinoid substrates
anandamide
periaqueductal gray
antinociception
title_short Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
title_full Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
title_fullStr Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
title_full_unstemmed Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
title_sort Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
author Mascarenhas, Diego C. [UNESP]
author_facet Mascarenhas, Diego C. [UNESP]
Gomes, Karina S. [UNESP]
Sorregotti, Tatiani [UNESP]
Nunes-de-Souza, Ricardo L. [UNESP]
author_role author
author2 Gomes, Karina S. [UNESP]
Sorregotti, Tatiani [UNESP]
Nunes-de-Souza, Ricardo L. [UNESP]
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Carlos (UFSCar)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Mascarenhas, Diego C. [UNESP]
Gomes, Karina S. [UNESP]
Sorregotti, Tatiani [UNESP]
Nunes-de-Souza, Ricardo L. [UNESP]
dc.subject.por.fl_str_mv vanilloid substrates
cannabinoid substrates
anandamide
periaqueductal gray
antinociception
topic vanilloid substrates
cannabinoid substrates
anandamide
periaqueductal gray
antinociception
description Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA) within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1) and Cannabinoid type 1 (CB1) receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG) of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist), capsaicin (TRPV1 agonist), WIN (CB1 agonist), AM251 (CB1 antagonist), and 6-iodonordihydrocapsaicin (6-IODO) (TRPV1 selective antagonist) and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB) substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1-and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.
publishDate 2017
dc.date.none.fl_str_mv 2017-10-04
2018-11-26T15:45:29Z
2018-11-26T15:45:29Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fphar.2017.00695
Frontiers In Pharmacology. Lausanne: Frontiers Media Sa, v. 8, 11 p., 2017.
1663-9812
http://hdl.handle.net/11449/159854
10.3389/fphar.2017.00695
WOS:000412243800001
WOS000412243800001.pdf
url http://dx.doi.org/10.3389/fphar.2017.00695
http://hdl.handle.net/11449/159854
identifier_str_mv Frontiers In Pharmacology. Lausanne: Frontiers Media Sa, v. 8, 11 p., 2017.
1663-9812
10.3389/fphar.2017.00695
WOS:000412243800001
WOS000412243800001.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers In Pharmacology
1,587
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eu_rights_str_mv openAccess
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application/pdf
dc.publisher.none.fl_str_mv Frontiers Media Sa
publisher.none.fl_str_mv Frontiers Media Sa
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
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instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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