Inhibition of S100A4 decreases neurotoxic astrocyte reactivity and attenuates neuropathic pain via the TLR4/NF-κB pathway in a rat model of spinal nerve ligation.

ABSTRACT: S100A4 participates in inflammation and immune reactions in the central nervous system and is involved in the pathogenesis of multiple neurological disorders. It can affect the functions of astrocytes, microglia, infiltrating cells and neurons and further modulates neuronal plasticity and survival in the central nervous system. However, its impact on astrocyte phenotypes and neuropathic pain and the intrinsic mechanisms involved remain poorly understood. Here, we showed that S100A4 was markedly upregulated after spinal nerve ligation and was mainly expressed in neurons in the spinal dorsal horn. Transcriptional inhibition of S100A4 with niclosamide attenuated neuropathic pain after surgery. We found that astrocytes differentiated into C3-positive reactive populations, so-called neurotoxic

SUBMITTER: Xue T 

PROVIDER: S-EPMC12044810 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature