DOI: 10.1177/17448069261504906 ISSN: 1744-8069

Electroacupuncture alleviates TNBS-induced visceral pain and modulates cortical EEG rhythms in association with TREM1/DAP12 pathway inhibition: Enhanced effects with pharmacological TREM1 blockade

Kaixin Wang, Daling Deng, Rui Yu, Tianhao Zhang, Jiwei Shen, Xiaojin Li, Shiwen Fan, Xiangdong Chen
Show PDF Cite

Background

Visceral pain in inflammatory bowel disease (IBD) lacks effective therapies. Whether the TREM1/DAP12 pathway is associated with electroacupuncture (EA) analgesia and cortical EEG modulation remains unclear.

Objective

To determine if spinal TREM1/DAP12 is associated with EA’s analgesic and neuromodulatory effects in TNBS-induced visceral pain.

Methods

Male Sprague-Dawley rats with TNBS-induced colitis received EA (ST36/ST37), the TREM1 inhibitor Nangibotide, or their combination. Behaviors (PWT, CRD, DAI), spinal TREM1/DAP12, downstream inflammatory mediators, and microglial colocalization were evaluated. Cortical EEG was analyzed using normalized power spectral density (Normalized PSD, %).

Results

EA significantly alleviated visceral/referred hyperalgesia and reduced DAI scores ( P < 0.05). TNBS upregulated spinal TREM1, DAP12, TNF-α, NLRP3, and TLR4 and increased TREM1/DAP12 microglial colocalization ( P < 0.0001), all reversed by EA (P < 0.001). Nangibotide alone partially mimicked EA’s effects, and their combination yielded greater analgesia and molecular suppression ( P < 0.05). Normalized EEG analysis revealed that TNBS increased δ power ( P < 0.0001) and reduced θ and β power ( P < 0.001). Notably, EA and Nangibotide specifically reversed δ elevation and restored θ power ( P <0.05) without altering β power ( P > 0.05), with greater δ suppression than either treatment alone ( P < 0.0001).

Conclusion

EA alleviates TNBS visceral pain and normalizes cortical δ/θ dysrhythmia, with these effects associated with suppression of microglial TREM1/DAP12 neuroinflammation. Pharmacological TREM1 blockade mimics and enhances EA’s effects, supporting this pathway as a promising therapeutic target for visceral pain.

More from our Archive