Neuroscience 2005 Abstract
| Presentation Number: | 622.3 |
|---|---|
| Abstract Title: | Cannabinoids inhibit capsaicin-sensitive neurons via heterologous desensitization mediated by the TRPA1/TRPV1 heteromers. |
| Authors: |
Ruparel, N. B.*1
; Akopian, A. N.3
; Patwardhan, A. M.2
; Jeske, N. A.3
; Hargreaves, K. M.1,2,3
1Cellular and Structural Biology, UTHSCSA, San Antonio, TX 2Pharmacology, UTHSCSA, San Antonio, TX 3Endodontics, UTHSCSA, San Antonio, TX |
| Primary Theme and Topics |
Sensory and Motor Systems - Pain -- Pain transduction molecules and channels |
| Session: |
622. Pain Transduction Molecules and Channels II Poster |
| Presentation Time: | Tuesday, November 15, 2005 10:00 AM-11:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # V2 |
| Keywords: | TRPA1, TRPV1, cannabinoid, pain |
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 immunoprecipitation with either anti-TRPA1 or anti-TRPV1 from co-transfected CHO cells as well as trigeminal ganglia. We further demonstrated that: 1) WIN inhibits capsaicin currents (Icap) in TG neurons; 2) a calcineurin antagonist blocks WIN inhibition of Icap in sensory neurons; and 3) WIN inhibits capsaicin-induced currents (Icap) in CHO cells only when TRPA1 and TRPV1 are co-transfected.
Collectively, these studies indicate that cannabinoids inhibit nociceptors via heterologous desensitization mediated by the TRPA1/TRPV1 heteromer. These findings may have considerable significance in the mechanisms of peripheral cannabinoid analgesia and antinociception and in developing novel analgesics devoid of classical cannabinoid side-effects.
Collectively, these studies indicate that cannabinoids inhibit nociceptors via heterologous desensitization mediated by the TRPA1/TRPV1 heteromer. These findings may have considerable significance in the mechanisms of peripheral cannabinoid analgesia and antinociception and in developing novel analgesics devoid of classical cannabinoid side-effects.
Supported by DA 11959 to KMH, DE 14928 to ANA and DE 016500 to NAJ
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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