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Papers of the Week

Papers: 15 Jun 2024 - 21 Jun 2024

2024 Jun 18

J Clin Invest


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Peripheral gating of mechanosensation by glial diazepam binding inhibitor.


Li X, Prudente AS, Prato V, Guo X, Hao H, Jones F, Figoli S, Mullen P, Wang Y, Tonello R, Lee SH, Shah S, Maffei B, Berta T, Du X, Gamper N


We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly expressed in satellite glia cells (SGCs) of mice, rat and human, 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 GABAA receptors, particularly strongly effecting 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 to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.