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bioRxiv · 10.1101/2020.05.21.109538

Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice

Yi, M.-H.·Liu, Y. U.·Liu, K.·Chen, T.·Bosco, D. B.·Zheng, J.·Xie, M.·Zhou, L.·Qu, W.·Wu, L.-J.
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Abstract

Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and the development of neuropathic pain in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CX3CR1creER/+:R26LSL-hM4Di/+ transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) exclusively in microglia. We found that microglial Gi DREADD activation inhibited spinal nerve transection (SNT)-induced microglial reactivity as well as chronic pain initiation and maintenance. Gi DREADD activation downregulated the transcription factor interferon regulatory factor 8 (IRF8) and its downstream target pro-inflammatory cytokine interleukin 1 beta (IL-1{beta}). Using in vivo spinal cord recording, we found that activation of microglial Gi DREADD attenuated synaptic transmission following SNT. Our results demonstrate that microglial Gi DREADD reduces neuroinflammation, synaptic function and neuropathic pain after peripheral nerve injury. Thus, chemogenetic approaches provide a potential opportunity for interrogating microglial function and neuropathic pain treatment.

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Yi, M.-H., Liu, Y. U., Liu, K., Chen, T., Bosco, D. B., Zheng, J., Xie, M., Zhou, L., Qu, W., Wu, L.-J.. 2020-05-22. Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice. https://doi.org/10.1101/2020.05.21.109538

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