Anti-Inflammatory and Analgesic Effects of Transdermal Tongluo Guzhining, a Traditional Chinese Medicine Patch, on Neuropathic Pain

Background: Neuropathic pain (NP) is a chronic and debilitating condition characterized by persistent neuroinflammation, for which current therapeutic options offer limited efficacy and tolerability. Traditional Chinese medicine (TCM) provides a multi-targeted approach to treatment. Tongluo Guzhining Patch (TGP) has been used clinically for pain management; however, its effect on NP remains unclear. Methods: This study combined network pharmacology with experimental validation to investigate the therapeutic potential of TGP. Computational analyses were performed to predict potential molecular targets and signaling pathways modulated by TGP. Subsequently, a chronic constriction injury (CCI) rat model was used to assess analgesic effects. Behavioral assessments, histopathological analyses, enzyme-linked immunosorbent assays (ELISA), quantitative polymerase chain reaction (qPCR), and Western blotting were conducted to evaluate inflammatory responses and the expression of key signaling molecules. Results: Network pharmacology analysis identified inflammation-associated pathways, with the interleukin-17 (IL-17) signaling pathway among the enriched pathways potentially targeted by TGP. In vivo experiments showed that TGP significantly attenuated mechanical allodynia and reduced inflammatory cell infiltration in CCI rats, as confirmed by histological analysis. Furthermore, TGP markedly decreased the levels of pro-inflammatory cytokines IL-1β and IL-6 in dorsal root ganglia and spinal cord tissues. Additionally, both mRNA and protein expression levels of IL-17A, IL-17 receptor A (IL-17RA), IL-6, and tumor necrosis factor-alpha (TNF-α) were significantly downregulated following TGP treatment. Conclusion: The findings indicate that TGP exerts potent anti-inflammatory and analgesic effects in a CCI-induced neuropathic pain model, likely through multi-target modulation of the IL-17-mediated inflammatory network. These results provide mechanistic insights supporting the therapeutic potential of TGP as an alternative treatment modality and underscore the IL-17 signaling pathway as a promising target for neuropathic pain intervention. Keywords: neuropathic pain, Tongluo Guzhining patch, Traditional Chinese medicine, IL-17 signaling pathway, neuroinflammation network pharmacology