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bioRxiv · 10.1101/2024.12.05.627015

Interleukin-4 induces CD11c+ microglia leading to amelioration of neuropathic pain in mice

Kohno, K.·Shirasaka, R.·Hirose, K.·Masuda, T.·Tsuda, M.
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Abstract

Neuropathic pain, a debilitating chronic pain condition, is a major clinical challenge. The pleiotropic cytokine interleukin-4 (IL-4) has been shown to suppress neuropathic pain in rodent models, but its underlying mechanism remains unclear. Here, we show that intrathecal administration of IL-4 to mice with spinal nerve transection (SpNT) increased the number of CD11c+ microglia (a microglia subset important for pain remission) in the spinal dorsal horn (SDH) and that this effect of IL-4 was essential for its ameliorating effect on SpNT-induced pain hypersensitivity. Furthermore, in mice with spared nerve injury (SNI), another model in which pain remission does not occur, the emergence of CD11c+ SDH microglia was curtailed, but intrathecal IL-4 increased their emergence and ameliorated pain hypersensitivity in a CD11c+ microglia-dependent manner. Our study reveals a mechanism by which intrathecal IL-4 ameliorates pain hypersensitivity after nerve injury and provides evidence that IL-4 increases CD11c+ microglia with a function that ameliorates neuropathic pain.

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Kohno, K., Shirasaka, R., Hirose, K., Masuda, T., Tsuda, M.. 2024-12-09. Interleukin-4 induces CD11c+ microglia leading to amelioration of neuropathic pain in mice. https://doi.org/10.1101/2024.12.05.627015

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