Scholarlink

Background <p>The mechanisms underlying neuropathic pain in traumatic neuromas following peripheral nerve injury have become a major research focus in the field of pain medicine. Transforming growth factor-β1 (TGF-β1), an anti-inflammatory cytokine, is significantly elevated in the dorsal root ganglion (DRG) after peripheral nerve injury. This study investigates the role and mechanisms of TGF-β1 in traumatic neuroma formation and neuropathic pain.</p> Methods <p>In vivo, neuropathic pain-related behaviors, neuroma formation, activation of nerve fibers in the dorsal root ganglion (DRG), and macrophage polarization were evaluated in rats subjected to sciatic nerve transection (SNT) to examine whether TGF-β1 plays a role in preventing traumatic neuroma. In vitro, RAW 264.7 cells were stimulated with lipopolysaccharide (LPS) (500&#xa0;ng/mL) to simulate traumatic neuroma-induced pathological changes in DRG macrophages, aiming to assess whether TGF-β1 alters the balance of macrophage polarization.</p> Results <p>In vivo, rapamycin (RAPA) treatment effectively reduced neuroma formation and alleviated neuropathic pain in rats, whereas these therapeutic effects were reversed upon inhibition of TGF-β1. In vitro, rapamycin treatment downregulated the expression of M1-related proteins (TNF-α, iNOS, and IL-1β) while upregulating M2-related proteins (Arg1 and IL-10). These effects were largely abolished when TGF-β1 siRNA was introduced. Furthermore, supplementation with exogenous recombinant TGF-β1 again reversed the M1/M2 polarization balance.</p> Conclusions <p>These findings suggest that TGF-β reduces the M1/M2 macrophage ratio by mediating the polarization direction of macrophages within DRGs. This mechanism may block the transmission of peripheral nociceptive signals, thereby promoting the repair of nerve injury. The study provides concrete evidence to guide the development of new therapeutic strategies for painful neuroma.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Regulation of macrophages in the dorsal root ganglion through TGF-β1 inhibits painful traumatic neuroma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月21日

查看全文
  • Chuanpeng Xia,
  • Jinghao Liang,
  • Ke Wang,
  • Anhao Guo,
  • Yu Chen,
  • Mazhar Ali Raza,
  • Long Wu,
  • Hede Yan

摘要

Background

The mechanisms underlying neuropathic pain in traumatic neuromas following peripheral nerve injury have become a major research focus in the field of pain medicine. Transforming growth factor-β1 (TGF-β1), an anti-inflammatory cytokine, is significantly elevated in the dorsal root ganglion (DRG) after peripheral nerve injury. This study investigates the role and mechanisms of TGF-β1 in traumatic neuroma formation and neuropathic pain.

Methods

In vivo, neuropathic pain-related behaviors, neuroma formation, activation of nerve fibers in the dorsal root ganglion (DRG), and macrophage polarization were evaluated in rats subjected to sciatic nerve transection (SNT) to examine whether TGF-β1 plays a role in preventing traumatic neuroma. In vitro, RAW 264.7 cells were stimulated with lipopolysaccharide (LPS) (500 ng/mL) to simulate traumatic neuroma-induced pathological changes in DRG macrophages, aiming to assess whether TGF-β1 alters the balance of macrophage polarization.

Results

In vivo, rapamycin (RAPA) treatment effectively reduced neuroma formation and alleviated neuropathic pain in rats, whereas these therapeutic effects were reversed upon inhibition of TGF-β1. In vitro, rapamycin treatment downregulated the expression of M1-related proteins (TNF-α, iNOS, and IL-1β) while upregulating M2-related proteins (Arg1 and IL-10). These effects were largely abolished when TGF-β1 siRNA was introduced. Furthermore, supplementation with exogenous recombinant TGF-β1 again reversed the M1/M2 polarization balance.

Conclusions

These findings suggest that TGF-β reduces the M1/M2 macrophage ratio by mediating the polarization direction of macrophages within DRGs. This mechanism may block the transmission of peripheral nociceptive signals, thereby promoting the repair of nerve injury. The study provides concrete evidence to guide the development of new therapeutic strategies for painful neuroma.