The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin.

ABSTRACT: Cannabinoids can evoke antihyperalgesia and antinociception at a peripheral site of action. However, the signaling pathways mediating these effects are not clearly understood. We tested the hypothesis that certain cannabinoids directly inhibit peripheral capsaicin-sensitive nociceptive neurons by dephosphorylating and desensitizing transient receptor potential vanilloid 1 (TRPV1) via a calcium calcineurin-dependent mechanism. Application of the cannabinoid WIN 55,212-2 (WIN) to cultured trigeminal (TG) neurons or isolated skin biopsies rapidly and significantly inhibited capsaicin-activated inward currents and neuropeptide exocytosis by a mechanism requiring the presence of extracellular calcium. The inhibitory effect did not involve activation of G protein-coupled cannabinoid receptors, b

SUBMITTER: Patwardhan AM 

PROVIDER: S-EPMC1544096 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature