Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , |
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. |
id |
UNSP_f7625a9e60704b37a28ca7d4134d4a26 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/159854 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 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) instacron:UNESP |
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) |
repository.mail.fl_str_mv |
|
_version_ |
1808128602575732736 |