Background & Aims

Fibromyalgia (FM) presents as a complex and widespread pain symptoms, significantly impacting patients’ emotional well-being, sleep quality, and fatigue levels, particularly among women aged 55 to 64. Treatment options include antidepressants, anticonvulsants, and various complementary therapies such as acupuncture, massage, psychological therapy, and exercise. Transient Receptor Potential Vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) receptors colocalize in microglia, generating detrimental sensory input in both the peripheral and central nervous systems. While electroacupuncture (EA) shows promise in alleviating FM pain, its underlying mechanisms, particularly its connection to pain signaling via TRPV1 and TLR4, remain unclear. This study induced FM-like pain using intermittent cold stress over 7, 14, and 21 days, along observing TRPV1 gene deletion effects on TRPV1 expression. Our results demonstrated a significant increase in the expression of TLR4 and TRPV1, al

Methods

The research involved female adult mice divided into five groups and subjected to intermittent cold stress to induce widespread pain. Behavioral tests, including thermal and mechanical tests, were conducted to assess their pain thresholds before sacrifice.

Results

Mouse ICS model stimulated the release of proinflammatory cytokines in plasma (Elisa test-1). Electroacupuncture treatment meaningfully reduced inflammatory cytokine levels. These cytokines were not reduced in the Sham group (1). EA and Trpv1 knockout significantly reduced mechanical and thermal hypersensitivity in chronic fibromyalgia. But Sham EA can not change this hypersensitivity. S100B and HMGB1 are secreted by astrocytes or microglial cells in the central nervous system after ICS-induced fibromyalgia. These neurotransmitters bind to TLR2, TLR4, RAGE, and TRPV1 receptors (2). The expression of TRPV1 was not increased in the KO mice. The normal level of TRPV1 in mPFC neurons was changed in the FM group, but this change was regulated by EA treatment and the TRPV1-/- group. But it cannot be seen in the Sham group. TLR4 colocalization in microglia. Microglial activation increased after FM induction, was reduced by low-frequency EA, but was not altered by the Sham group. (1)

Conclusions

Our investigation into electroacupuncture at 2-Hz at ST36 acupoints for FM utilized intermittent cold stress to simulate pain, focusing on TRPV1 and TLR4 pathways. We found that low-frequency electroacupuncture significantly reduced pain sensitivity over a 7 to 21-day period in mice. This treatment also decreased inflammatory mediators and downregulated TRPV1 and TLR4 receptor expression. Notably, sham electroacupuncture had no effect, highlighting the specific therapeutic benefits of electroacupuncture in managing fibromyalgia-like pain by modulating these pathways.

References

1. Lai P-C, Yen C-M, Lin M-C, Chen Y-H, Liao H-Y, Huang Y-W, Lin Y-W. Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain. Life. 2023; 13(5):1160. 2. Hsiao IH, Lin YW. Electroacupuncture Reduces Fibromyalgia Pain by Attenuating the HMGB1, S100B, and TRPV1 Signalling Pathways in the Mouse Brain. Evid Based Complement Alternat Med. 2022;2022:2242074. Published 2022 Mar 15.

Presenting Author

Ngoc Anh Doan Thi

Poster Authors

Ngoc Anh Doan Thi

PhD

College of Chinese Medicine, Graduate Institute of Acupuncture Science

Lead Author