Neuroscience 2003 Abstract
| Presentation Number: | 907.11 |
|---|---|
| Abstract Title: | Anti- and pro-nociceptive effects of cannabinoids through CB1 and TRPV1 receptors in rats and transgenic mice. |
| Authors: |
Engel, M. A.*1
; Reeh, P. W.1
1Physiology I, Univ. Erlangen-Nuremberg, Erlangen, Germany |
| Primary Theme and Topics |
Sensory Systems - Pain -- Nociceptors |
| Secondary Theme and Topics | Sensory Systems<br />- Pain<br />-- Genomic/transgenic approaches |
| Session: |
907. Pain: TRP Channel Pharmacology Poster |
| Presentation Time: | Wednesday, November 12, 2003 3:00 PM-4:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # E9 |
| Keywords: | Neurogenic Inflammation, Anandamide, THC, CGRP |
The cannabinoids R-(+)-methanandamide (mAEA) and (-)-Δ9-tetrahydrocannabinol (THC) have been suggested to exert direct effects on nociceptive primary afferents by activating cannabinoid (CB1) receptors at low and vanilloid (TRPV1) receptors at higher concentrations. We studied pretreatment (5 min) effects of both compounds on capsaicin, noxious heat and potassium responses of isolated hindpaw skin of rats and transgenic mice measuring stimulated iCGRP release (EIA).
Both compounds 0.1 µM showed significant desensitizations to capsaicin and heat by 42% and 32%, respectively, which were absent in CB1-/- and unchanged in TRPV1-/- mice. Concentrations >1 µM exhibited concentration-dependent intrinsic effects (mAEA>THC) which culminated at 100 µM in marked cross-desensitization to capsaicin and heat, absent in TRPV1-/- (using THC) and unchanged in CB1-/- (using both compounds). At 1 µM THC showed a small inhibitory and mAEA no effect, suggesting a balance between CB1 and TRPV1 actions. At 10 µM both compounds caused a significant sensitization to capsaicin, absent in TRPV1-/-, but not to heat. The cannabinoids had no influence on the potassium responses except for additive intrinsic effects at higher concentrations.
We conclude that the cannabinoids in our model exert anti-nociceptive effects through the CB1 receptor without a major contribution of the CB2 receptor co-activated by THC. Pro-nociceptive effects -also of THC- result from activation of the capsaicin receptor with no contribution from other heat-activated ion channels that appear insensitive to the endogenous mediator anandamide.
Both compounds 0.1 µM showed significant desensitizations to capsaicin and heat by 42% and 32%, respectively, which were absent in CB1-/- and unchanged in TRPV1-/- mice. Concentrations >1 µM exhibited concentration-dependent intrinsic effects (mAEA>THC) which culminated at 100 µM in marked cross-desensitization to capsaicin and heat, absent in TRPV1-/- (using THC) and unchanged in CB1-/- (using both compounds). At 1 µM THC showed a small inhibitory and mAEA no effect, suggesting a balance between CB1 and TRPV1 actions. At 10 µM both compounds caused a significant sensitization to capsaicin, absent in TRPV1-/-, but not to heat. The cannabinoids had no influence on the potassium responses except for additive intrinsic effects at higher concentrations.
We conclude that the cannabinoids in our model exert anti-nociceptive effects through the CB1 receptor without a major contribution of the CB2 receptor co-activated by THC. Pro-nociceptive effects -also of THC- result from activation of the capsaicin receptor with no contribution from other heat-activated ion channels that appear insensitive to the endogenous mediator anandamide.
Supported by TRPV1 -/- generously provided by John B. Davis, GSK, Harlow (UK) and CB1-/- by Andreas Zimmer, University Bonn, Bonn (Germany); funded by DFG-SFB 353/B12
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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