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Peripheral gating of mechanosensation by glial diazepam binding inhibitor
- Source :
- Journal of Clinical Investigation. August 15, 2024, Vol. 134 Issue 16
- Publication Year :
- 2024
-
Abstract
- We report that diazepam binding inhibitor (DBI) is a glial messenger mediating crosstalk between satellite glial cells (SGCs) and sensory neurons in the dorsal root ganglion (DRG). DBI is highly expressed in SGCs of mice, rats, and humans, but not in sensory neurons or most other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without major effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as an unconventional agonist and positive allosteric modulator at the neuronal [GABA.sub.A] receptors, particularly strongly affecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons, and these are also more enwrapped with DBI-expressing glia, as compared with other DRG neurons, suggesting a mechanism for a specific effect of DBI on mechanosensation. These findings identified a communication mechanism between peripheral neurons and SGCs. This communication modulates pain signaling and can be targeted therapeutically.<br />Introduction Despite remarkable progress in our understanding of the fundamental biology of pain, current therapies for chronic pain are often inadequate and prone to serious side effects within the central [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 134
- Issue :
- 16
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.808510058
- Full Text :
- https://doi.org/10.1172/JCI176227