Cannabinoids have been shown to produce a peripherally mediated antihyperalgesia and antinociception, yet metabotropic cannabinoid receptors, CB1 and CB2 are expressed in <5% of nociceptors (i.e. TRPV1 positive neurons). We have shown that cannabinoids activate calcineurin leading to TRPV1 dephosphorylation and peripheral antihyperalgesia and antinociception (see 2005 SFN abstracts by Jeske et. al. and Patwardhan et. al.). Therefore, we have sought to investigate whether ionotropic cannabinoid receptors mediate inhibition of capsaicin-sensitive neurons. Application of the dual cannabinoid agonist WIN 55,212 (WIN) generated inward currents (IWIN) in a subset of small-to-medium sized trigeminal ganglion (TG) neurons. Using transfected CHO cells and patch clamp analysis, we demonstrated that: 1) WIN activates TRPA1, but not TRPV1; and 2) co-expression of TRPA1 and TRPV1 was required to account for properties of neuronal IWIN. The formation of a tight TRPA1/TRPV1 heteromeric complexes was demonstrated by immun...