CBLN1 inhibits the inflammatory response by targeting GluD1 thereby alleviating resiniferatoxin-induced postherpetic neuralgia in mice.

Postherpetic neuralgia (PHN) is a chronic, treatment-resistant pain condition following herpes zoster. Neuroinflammation plays a key role in its pathogenesis but the mechanisms are unclear. Cerebellin-1 (CBLN1), a synaptic protein of the C1q/TNF family, may modulate pain via interaction with GluD1. However, its role in PHN progression is also unclear. Herein, we investigated the role of CBLN1 in resiniferatoxin (RTX)-induced PHN in mice and uncover the mechanism. We found that CBLN1 was downregulated in the spinal dorsal horn of PHN model mice. Recombinant CBLN1 administration alleviated RTX-induced mechanical and thermal hypersensitivity, reduced proinflammatory cytokine levels, and decreased neuronal apoptosis. It also increased GluD1 expression. These effects were abolished by GluD1 inhibition, suggesting that CBLN1 exerts its protective role via the GluD1 pathway. Therefore, CBLN1 inhibits the inflammatory response by targeting GluD1 thereby alleviating RTX-induced postherpetic neuralgia in mice.