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

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 m...

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Main Authors: Keita Kohno, Ryoji Shirasaka, Keita Hirose, Takahiro Masuda, Makoto Tsuda
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-08-01
Series:eLife
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Online Access:https://elifesciences.org/articles/105087
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Summary: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.
ISSN:2050-084X