2. Academic Validation
  3. Overexpression of TAFA4 in the dorsal root ganglion ameliorates neuropathic pain in male rats through promoting macrophage M2-Skewing

Overexpression of TAFA4 in the dorsal root ganglion ameliorates neuropathic pain in male rats through promoting macrophage M2-Skewing

  • Neurochem Int. 2025 Jul:187:105993. doi: 10.1016/j.neuint.2025.105993.
Zhangran Ai 1,  Huili Li 1,  Songchao Xu 1,  Chenghui Cai 1,  Xuejuan Wang 1,  Yun Guan 2,  Ruijuan Guo 3,  Yun Wang 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
  • 2 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • 3 Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: guoguo12015@163.com.
  • 4 Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: wangyun129@ccmu.edu.cn.
PMID: 40381955 DOI: 10.1016/j.neuint.2025.105993
Abstract

Neuro-immune interactions between macrophages and primary sensory neurons have been implicated in nerve injury and associated pain. This study aims to explore the function of the TAFA4 as a crucial neuroimmune regulator in modulating macrophage states within the context of neuropathic pain. To elucidate the role of TAFA4 in dorsal root ganglia (DRG) following a chronic constriction injury (CCI) model in male rats, immunofluorescent staining, western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were performed. Microinjection of self-complementary adeno-associated virus expressing TAFA4 mRNA into the L4 and L5 DRGs was conducted to overexpress TAFA4 in the DRGs. Following peripheral nerve injury, we observed a downregulation of TAFA4 in ipsilateral DRG neurons. Restoring this downregulation effectively alleviated the mechanical and thermal nociceptive hypersensitivity by inhibiting pro-inflammatory mediators while promoting the secretion of anti-inflammatory cytokines on day 14 post-CCI. Notably, scAAV-TAFA4 microinjection also facilitated the polarization of macrophages in the DRGs towards the M2 phenotype. Mechanistically, TAFA4 modulates the functions of macrophages in a lipoprotein receptor-related protein 1-dependent manner. Our findings revealed the role of TAFA4 in shifting macrophages in favor of an anti-inflammatory phenotype and enhancing interleukin 10 concentrations in the DRG, suggesting it is a potential analgesic target for alleviating neuropathic pain.

Keywords

Cytokine; Dorsal root ganglia; Macrophage; Neuropathic pain; TAFA4.

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