Trpv1 Reporter Mice Reveal Highly Restricted Brain Distribution and Functional Expression in Arteriolar Smooth Muscle Cells
Open accessAbstract
The heat and capsaicin receptor, TRPV1, is required for the detection of painful heat by primary afferent pain fibers (nociceptors), but the extent to which functional TRPV1 channels are expressed in the CNS is debated. Because previous evidence is based primarily on indirect physiological responses to capsaicin, here we genetically modified the Trpv1 locus to reveal, with excellent sensitivity and specificity, the distribution of TRPV1 in all neuronal and non-neuronal tissues. In contrast to reports of widespread and robust expression in the CNS, we find that neuronal TRPV1 is primarily restricted to nociceptors in primary sensory ganglia, with minimal expression in a few discrete brain regions, most notably in a contiguous band of cells within and adjacent to the caudal hypothalamus. We confirm hypothalamic expression in the mouse using several complementary approaches, including in situ hybridization, calcium imaging, and electrophysiological recordings. Additional in situ hybridization experiments in rat, monkey, and human brain demonstrate that the restricted expression of TRPV1 in the CNS is conserved across species. Outside of the CNS, we find TRPV1 expression in a subset of arteriolar smooth muscle cells within thermoregulatory tissues. Here, capsaicin increases calcium uptake and induces vasoconstriction, an effect that likely counteracts the vasodilation produced by activation of neuronal TRPV1.
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Mouse reporter lines generated to visualize TRPV1 found distinct and sparsely distributed TRPV1-positive neurons in anxiety-mediating brain areas including the periaqueductal grey, hypothalamus, and hippocampus.
“Mouse reporter lines generated to visualize TRPV1 found distinct and sparely distribution of TRPV1-positive neurons in anxiety-mediating brain areas including the periaqueductal grey (PAG), hypothalamus and hippocampus (Cavanaugh et al., 2011).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Cavanaugh et al., 2011
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- Authors
- Cavanaugh, D. J., Chesler, A. T., Jackson, A. C., Sigal, Y. M., Yamanaka, H., Grant, R., O'Donnell, D., Nicoll, R. A., Shah, N. M., Julius, D., & Basbaum, A. I.
- Affiliations
- University of San Francisco (US)
- University of California, San Francisco (US)
- AstraZeneca (Canada) (CA)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-30
- Volume
- 31
- Issue
- 13
- Pages
- 5067-5077
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3087977
- OpenAlex
- W2099414466
- Cited by
- 542
- References
- 38
- Citations by year
- 2026: 19 · 2025: 32 · 2024: 39 · 2023: 37 · 2022: 30 · 2021: 41 · 2020: 31 · 2019: 33 · 2018: 38 · 2017: 41 · 2016: 31 · 2015: 28 · 2014: 48 · 2013: 41 · 2012: 34
- FWCI
- 24.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- National Institutes of Health (DP1OD006425, NS14627)
- University of California, San Francisco
- National Institute of Mental Health (F32MH081430, DP1MH099900, R37MH038256)
- National Institute of Neurological Disorders and Stroke (R01NS014627, R37NS014627, NS 14627, R37NS047723, R01NS049488)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- TRPV1, capsaicin receptor, nociceptors, caudal hypothalamus, vasoconstriction, calcium uptake, species conservation
- MeSH terms
- Animals, Arterioles, Brain Chemistry, Gene Expression Regulation, Humans, Hypothalamus, Macaca fascicularis, Male, Mice, Transgenic, Vasoconstriction, Vasodilation, Rats, Sprague-Dawley, Genes, Reporter, Myocytes, Smooth Muscle, TRPV Cation Channels, Mice, Rats
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