Presentation Details
| TRPM8-mediated cool-induced analgesia in a mouse model of chemesthetic oro-trigeminal pain Chris Brooks, Christian Lemon. University of Oklahoma, Norman, OK, USA |
Abstract
Transient Receptor Potential Melastatin 8 (TRPM8) is a cool-activated cation channel found in sensory neurons within the trigeminal and dorsal root ganglia (DRG). TRPM8+ DRG neurons have been implicated in cool-induced analgesia, possibly via a gate-control mechanism whereby they block parallel nociceptive signals. However, the existence of a TRPM8-mediated analgesia effect in the oro-trigeminal system has not yet been investigated. Herein, we employed a mouse model of oro-trigeminal pain using the TRP Ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC, mustard oil) delivered in a concentration series (30uM, 100uM, 300uM, 1000uM) at 5°C, 15°C, and 35°C in brief access water licking trials using 23 mice (11 C57BL/6J, 12 TRPM8-KO). We hypothesized that C57 mice would show less aversion to the nociceptive AITC at 15°C than the KO mice, but not at 5°C or 35°C due to reduced activation of TRPM8. Wilcoxon rank-sum tests revealed significant between-genotype differences in lick rates in the 300uM-15°C (p=0.049) and 1000uM-15°C (p=0.029) conditions; in both cases the KO mice drank significantly less AITC than C57 mice. These data support our hypothesis that cool temperatures reduce the aversive effect of noxious AITC in the mouth, and that this effect is diminished in mice lacking TRPM8. TRPA1 is primarily expressed on cells that also express TRP Vanilloid 1 (TRPV1). We theorize that TRPM8+ fibers suppress TRPV1+ nociceptors via a central mechanism, e.g. the gate-control model observed in DRG. We plan to continue with capsaicin, a TRPV1 agonist, to clarify if the TRPM8-mediated cool suppression is indeed acting on TRPV1+ nociceptive fibers. We intend to explore the bitter (but not nociceptive) tastant quinine and TRPM8 agonist menthol to further discern what pathways and receptors may be involved.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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