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Group III mGluR8 negatively modulates TRPA1.
R M Govea1, S Zhou1, S M Carlton1
1Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1069, United States.
Neuroscience
|August 8, 2016
Summary
Group III metabotropic glutamate receptors (mGluRs) reduce pain sensitivity by inhibiting TRPA1 channels on nerve cells. This finding suggests mGluR agonists could treat mechanical hypersensitivity in various conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Group III metabotropic glutamate receptors (mGluRs) are known to have anti-hyperalgesic effects.
- Transient Receptor Potential Ankyrin 1 (TRPA1) channels are implicated in pain signaling.
- The interaction between mGluR8 and TRPA1 on nociceptors is not fully understood.
Purpose of the Study:
- To investigate the interaction between group III mGluRs (specifically mGluR8) and TRPA1 channels on cutaneous nociceptors.
- To determine if mGluR8 modulates TRPA1 channel activity and its role in mechanical hypersensitivity.
Main Methods:
- Utilized calcium (Ca2+) imaging in rat nociceptors to assess functional coupling between mGluR8 and TRPA1.
- Conducted behavioral studies in rats to evaluate the effects of mGluR8 agonists on TRPA1-mediated mechanical hypersensitivity.
- Performed single-fiber electrophysiology recordings from cutaneous nociceptors.
Main Results:
- mGluR8 agonists (DCPG) significantly reduced TRPA1 agonist (mustard oil)-induced Ca2+ mobilization and mechanical hypersensitivity.
- DCPG reversed TRPA1-mediated increases in nociceptor activity and decreased mechanical thresholds.
- Inhibition of protein kinase A (PKA) attenuated TRPA1-induced Ca2+ responses, suggesting a role for the cAMP/PKA pathway.
Conclusions:
- Group III mGluRs negatively modulate TRPA1 channel activity on cutaneous nociceptors.
- This modulation likely occurs intracellularly via the cAMP/PKA pathway.
- Group III mGluR agonists show potential for treating mechanical hypersensitivity associated with inflammation, nerve injury, and other conditions.
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