Spinal 5-HT_1A Receptor-Related and Microglial Mechanisms Associated With Intrathecal Cannabidiol-Induced Antinociception in Neuropathic Pain.

Authors

Sergio Saboia Junior, Rafaela Silva Dos Santos, Lívia Maria Ribeiro Rosário, Rayner Ribeiro Cardoso, Flávio Protasio Veras, João Paulo Prado, Ester Siqueira Caixeita Nogueira, Angel Roberto Barchuk, Thiago Roberto Lima Romero, Giovane Galdino

Published in

Archiv der Pharmazie. Volume 359. Issue 6. Pages e70282.

Abstract

Although first-line pharmacological treatments for neuropathic pain are often ineffective, cannabidiol has shown promise. However, the analgesic effects of orally administered, cannabidiol are limited by low bioavailability and a short half-life. Therefore, this study investigated the effects of intrathecal (i.t.), cannabidiol administration on neuropathic pain, focusing on spinal 5-HT_1A receptors and microglial modulation. Male C57BL/6 mice were subjected to neuropathic pain-induced by chronic constriction injury (CCI). Mechanical nociceptive thresholds were assessed using von Frey filaments. The involvement of spinal 5-HT_1A receptors was examined by i.t. administration of the selective antagonist WAY-100635. mRNA expression, IL-10, and TNF-α levels, and microglial activation were evaluated. Intrathecal, cannabidiol significantly reversed mechanical allodynia, producing a more potent and prolonged antinociceptive effect than oral administration. This effect was abolished by WAY-100635, indicating spinal 5-HT_1A receptor involvement. Moreover, i.t. cannabidiol increased spinal IL-10 levels and 5-HT_1A receptor mRNA expression, while reducing microglial activation. In vitro, cannabidiol attenuated microglial activation and significantly reduced TNF-α production. In conclusion, i.t. cannabidiol effectively alleviates neuropathic pain in mice, with findings that may suggest the involvement of spinal mechanisms associated with 5-HT_1A receptor-related signaling and modulation of microglial activation.

PMID:
42397162
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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