Journal
JOURNAL OF NEUROSCIENCE
Volume 41, Issue 36, Pages 7546-7560Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0195-21.2021
Keywords
cacna1b; calcium channel; conotoxin; hyperalgesia; N-type calcium channels; nociceptor
Categories
Funding
- National Institute of Neurological Disorders and Stroke [NS055251, F31NS093818, T32NS062443, K99NS116123, DP2-NS106664]
- National Institute of Mental Health [T32MH020068]
- Warren Alpert Foundation Fellowship Award
- New York Stem Cell Foundation [100003194]
- Robert J. and Nancy D. Carney Institute for Brain Science
Ask authors/readers for more resources
Functional Ca(V)2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity, which may be an important therapeutic target for certain forms of chronic pain.
Voltage-gated Ca(V)2.2 calcium channels are expressed in nociceptors at presynaptic terminals, soma, and axons. Ca(V)2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathologic pain, but a biological function of nociceptor Ca(V)2.2 channels in processing of nociception, outside presynaptic terminals in the spinal cord, is underappreciated. Here, we demonstrate that functional Ca(V)2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity in male and female mice. We show that Ca(V)2.2 channels in TRPV1-nociceptor endings are activated by capsaicin-induced depolarization and contribute to increased intracellular calcium. Capsaicin induces hypersensitivity of both thermal nociceptors and mechanoreceptors, but only heat hypersensitivity depends on peripheral Ca(V)2.2 channel activity, and especially a cell-type-specific Ca(V)2.2 splice isoform. Ca(V)2.2 channels at peripheral nerve endings might be important therapeutic targets to mitigate certain forms of chronic pain.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available