Peripherally injected canabidiol reduces neuropathic pain in mice: Role of the 5-HT1A and TRPV1 receptors

. 2023 Apr 11;660:58-64.

doi: 10.1016/j.bbrc.2023.04.022.

Online ahead of print.


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Danielle Diniz Aguiar et al.

Biochem Biophys Res Commun.



Cannabidiol (CBD) is the most abundant non-psychoactive component found in plants of the genus Cannabis. Its analgesic effect for the treatment of neuropathy has been widely studied. However, little is known about its effects in the acute treatment when Cannabidiol is administered peripherally. Because of that, this research was aimed to evaluate the antinociceptive effects of the CBD when administered peripherally for the treatment of acute neuropathic pain and check the involvement of the 5-HT1A and the TRPV1 receptors in this event. Neuropathic pain was induced with the constriction of the sciatic nerve while the nociceptive threshold was measured using the pressure test of the mouse paw. The technique used proved to be efficient to induce neuropathy, and the CBD (5, 10 and 30 μg/paw) induced the antinociception in a dosage-dependent manner. The dosage used that induced a more potent effect (30 μg/paw), did not induce a systemic response, as demonstrated by both the motor coordination assessment test (RotaRod) and the antinociceptive effect restricted to the paw treated with CBD. The administration of NAN-190 (10 μg/paw), a selective 5-HT1A receptor antagonist, and SB-366791 (16 μg/paw), a selective TRPV1 antagonist, partially reversed the CBD-induced antinociception. The results of the research suggest that the CBD produces the peripheral antinociception during the acute treatment of the neuropathic pain and it partially involved the participation of the 5-HT1A and TRPV1 receptors.


5-HT(1A) receptors; Cannabidiol; Neuropathic pain; Peripheral antinociception; TRPV1 receptors.

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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