Botulinum toxin type A inhibits chronic post-thoracotomy pain through the HMGB1-mediated TLR4/NF-kappaB signaling pathway
Am J Transl Res. 2026 Feb 15;18(2):976-987. doi: 10.62347/QOKY9197. eCollection 2026.
ABSTRACT
OBJECTIVE: To elucidate the analgesic role and underlying mechanism of botulinum toxin type A (BTX-A) in chronic post-thoracotomy pain (CPTP).
METHODS: Postoperative wound scar tissues were collected from patients with and without CPTP. Histopathologic changes were evaluated using hematoxylin-eosin (H&E) staining, and the expression levels of high mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were assessed. Spinal microglia were cultured in vitro to establish a cell model of CPTP. The activated microglial cells were then treated with BTX-A to evaluate its effects on substance P (SP)-induced microglia activation, HMGB1 expression, TLR4/NF-κB pathway, and inflammatory cytokine (TNF-α and IL-10) secretion. Additionally, microglia were transfected with an HMGB1 lentiviral vector to assess the regulatory role of HMGB1 on TLR4/NF-κB signaling, microglial activation, cytokine release, and the inhibitory effects of BTX-A.
RESULTS: H&E staining showed strong inflammatory cell infiltration and upregulated expression of HMGB1, TLR4, IL-10, and TNF-α in tissues from the CPTP group (P < 0.05). Transfection with HMGB1 lentiviral vector significantly increased the expression levels of TLR4, p-P65, and p-IκB-α in microglial cells, enhanced cell proliferation, and promoted IL-10 and TNF-α secretion. TLR4/NF-κB pathway activation positively regulated microglial activation and TNF-α and IL-10 expression. Moreover, HMGB1 overexpression attenuated the inhibitory effects of BTX-A on microglial activation.
CONCLUSIONS: BTX-A may alleviate post-thoracotomy pain by downregulating the HMGB1/TLR4/NF-κB pathway, thereby reducing the secretion of inflammatory factors and inhibiting microglial activation.
PMID:41868905 | PMC:PMC13000795 | DOI:10.62347/QOKY9197