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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Mascarenhas, Diego C. [1, 2, 3] ; Gomes, Karina S. [1] ; Sorregotti, Tatiani [1, 2, 3] ; Nunes-de-Souza, Ricardo L. [1, 2, 3]
Total Authors: 4
[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
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 0

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)

FAPESP's process: 13/01283-6 - Hierarchic defensive system in mice: role of the corticotrophin-releasing factor (CRF)
Grantee:Ricardo Luiz Nunes de Souza
Support type: Regular Research Grants
FAPESP's process: 13/06764-2 - Social defeat-induced antinociception: implication of spinal and supraspinal vanilloid neurotransmission in mice.
Grantee:Diego Cardozo Mascarenhas
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/03445-3 - Effects of corticotrophin releasing factor (CRF) overexpression and Crf1 and CRF2 receptors knockout within limbic structures on defensive behavior in mice: influence of acute and chronic stress
Grantee:Karina Santos Gomes
Support type: Scholarships abroad - Research Internship - Post-doctor