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
  • 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: [email protected].
  • 4. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: [email protected].
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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