Disulfiram alleviates inflammatory pain by suppressing TLR4/NF-κB signaling in sensory ganglia

Abstract

IntroductionInflammatory pain remains a major clinical challenge, and neuroimmune interactions within peripheral sensory ganglia contribute to its development. This study investigated whether disulfiram (DSF) alleviates inflammatory hypersensitivity and whether its effects are associated with modulation of TLR4/NF-κB-related signaling.MethodsComplete Freund's adjuvant (CFA)-induced hind paw and orofacial inflammatory pain models were established in mice. The effects of DSF administered via different routes were evaluated using behavioral assays. TLR4/NF-κB-related signaling and downstream inflammatory cytokines were examined in dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons and tissues using western blotting and ELISA.ResultsDSF treatment attenuated CFA-induced mechanical and thermal hypersensitivity and spontaneous nocifensive behaviors. In cultured DRG and TG neurons, DSF reduced LPS-induced phosphorylation of IKKβ, IκBα, and NF-κB p65. Consistently, DSF attenuated CFA-associated phosphorylation of these signaling proteins in DRG and TG tissues. Western blotting and ELISA further demonstrated reductions in the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α following DSF treatment.DiscussionThese findings suggest that the analgesic effects of DSF in experimental inflammatory pain models are associated with attenuation of TLR4/NF-κB-related signaling and downstream inflammatory responses in peripheral sensory ganglia. Further studies are warranted to clarify the underlying molecular mechanisms.

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BibTeX RIS

BibTeX

@article{wang2026disulfiram,
  title = {{Disulfiram alleviates inflammatory pain by suppressing TLR4/NF-κB signaling in sensory ganglia}},
  author = {Libin Wang and Liangjing Shu and Xiong Yan and Liusheng Hu and Yihong Li and Jinyu Xu and Kaifeng Luo and Qinqin Hu and Yun Tong},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = nov,
  doi = {10.3389/fimmu.2026.1891944},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1891944},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Disulfiram alleviates inflammatory pain by suppressing TLR4/NF-κB signaling in sensory ganglia
AU  - Libin Wang
AU  - Liangjing Shu
AU  - Xiong Yan
AU  - Liusheng Hu
AU  - Yihong Li
AU  - Jinyu Xu
AU  - Kaifeng Luo
AU  - Qinqin Hu
AU  - Yun Tong
PY  - 2026
DA  - 2026/11/04
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1891944
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1891944
AB  - IntroductionInflammatory pain remains a major clinical challenge, and neuroimmune interactions within peripheral sensory ganglia contribute to its development. This study investigated whether disulfiram (DSF) alleviates inflammatory hypersensitivity and whether its effects are associated with modulation of TLR4/NF-κB-related signaling.MethodsComplete Freund's adjuvant (CFA)-induced hind paw and orofacial inflammatory pain models were established in mice. The effects of DSF administered via different routes were evaluated using behavioral assays. TLR4/NF-κB-related signaling and downstream inflammatory cytokines were examined in dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons and tissues using western blotting and ELISA.ResultsDSF treatment attenuated CFA-induced mechanical and thermal hypersensitivity and spontaneous nocifensive behaviors. In cultured DRG and TG neurons, DSF reduced LPS-induced phosphorylation of IKKβ, IκBα, and NF-κB p65. Consistently, DSF attenuated CFA-associated phosphorylation of these signaling proteins in DRG and TG tissues. Western blotting and ELISA further demonstrated reductions in the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α following DSF treatment.DiscussionThese findings suggest that the analgesic effects of DSF in experimental inflammatory pain models are associated with attenuation of TLR4/NF-κB-related signaling and downstream inflammatory responses in peripheral sensory ganglia. Further studies are warranted to clarify the underlying molecular mechanisms.
SN  - 1664-3224
ER  -

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