Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
Mascarenhas, Diego C. [1, 2, 3] ; Gomes, Karina S. [1] ; Sorregotti, Tatiani [1, 2, 3] ; Nunes-de-Souza, Ricardo L. [1, 2, 3]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ, Sch Pharmaceut Sci, Lab Neuropsychopharmacol, Araraquara, SP - Brazil
[2] Univ Fed Sao Carlos, Joint Grad Program Physiol Sci, Sao Carlos, SP - Brazil
[3] Sao Paulo State Univ, Sao Carlos, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN PHARMACOLOGY; v. 8, OCT 4 2017.
Citações Web of Science: 0
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. (AU)

Processo FAPESP: 13/01283-6 - Sistema hierárquico de defesa no camundongo: modulação pelo fator de liberação de corticotrofina (CRF)
Beneficiário:Ricardo Luiz Nunes de Souza
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/06764-2 - A antinocicepção induzida pela derrota social: implicações da neurotransmissão vaniloide espinal e supraespinal em camundongos.
Beneficiário:Diego Cardozo Mascarenhas
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/03445-3 - Efeitos da superexpressão do Fator de Liberação de Corticotropina (CRF) e nocaute de receptores Crf1 e Crf2 em regiões límbicas sobre o comportamento defensivo de camundongos: influência do estresse agudo e crônico
Beneficiário:Karina Santos Gomes
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado