Background & Aims

Acupuncture has been widely used for chronic pain management and several systematic reviews demonstrated the effectiveness [1, 2]. Activation of distinct primary afferents has been reported to relieve pain via inhibiting spontaneous activities of spinal wide dynamic range (WDR) neurons in inflammatory muscle pain rats [3]. Importantly, neurons in the spinal dorsal horn (SDH) undergo sensitization, particularly windup and long-term potentiation (LTP), both of which are strongly associated with the development of allodynia and hyperalgesia [4, 5]. Nonetheless, it remains unclear that whether different intensities of EA can effectively attenuate the spinal neuronal sensitization by inhibiting the windup of WDR neurons and LTP during chronic pain, resulting in analgesic effects. The present study aims to investigate the potential mechanisms of distinct intensities of EA on spinal sensitization by measuring the windup of spinal WDR neurons and LTP in inflammatory muscle pain rats.

Methods

Complete Freund’s adjuvant (CFA) was injected into the left gastrocnemius muscle of rats to induce inflammatory muscle pain. EA at A?, A? and C intensities (EAA?, EAA? and EAC) were administered daily since the 3rd day post CFA injection. The weight-bearing, Randall-Selitto and von Frey were performed on the 1st, and 3rd to 5th days post injection to evaluate the spontaneous and mechanical stimulus-evoked pain. In vivo extracellular electrophysiological recordings were performed to observe the responsiveness of spinal WDR neurons as well as field potential.

Results

EA at intensity of both A? and C, but not A? significantly alleviated spontaneous and mechanical-evoked nociception in inflammatory muscular pain rats, while EAC exhibited a superior pain-relieving effect. Electrophysiological recordings revealed a significant increase in the responsiveness of spinal WDR neurons to mechanical and electrical stimuli in inflammatory muscle pain rats. Meanwhile, CFA-treated rats exhibited obvious windup in WDR neurons, as well as lowered threshold of C-fiber evoked field potential (CFEFP) and LTP of synaptic transmission. After EAA? and EAC interventions, the mechanical and electrical responsiveness of WDR neurons markedly decreased, accompanied by immediate and sustained reductions in the windup response of WDR neurons. Notably, EAC exhibited a more pronounced suppressive effect. Additionally, EAA? raised the threshold of spinal CFEFP, while EAC intervention also significantly alleviated the occurrence of LTP in rats with inflammatory muscle pain.

Conclusions

EA intervention exerted analgesic effects through reducing the responsiveness and sensitization of spinal dorsal horn neurons, with EAC demonstrating superior efficacy.

References

[1]Hershman Dawn L., Unger Joseph M., Greenlee Heather, Capodice Jillian, Lew Danika L., Darke Amy, Minasian Lori M., Fisch Michael J., Henry N. LynnCrew Katherine D. Comparison of Acupuncture Vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor-Related Joint Pain: A Randomized Clinical Trial. JAMA Network Open, 2022, 5(11),e2241720.
[2]Li Pei Shuang, Peng Xue Mei, Niu Xiang Xin, Xu Ling, Hung Yu Ng Ernest, Wang Chi Chiu, Dai Jin Fang, Lu JunLiang Rui Ning. Efficacy of Acupuncture for Endometriosis-Associated Pain: A Multicenter Randomized Single-Blind Placebo-Controlled Trial. Fertility and Sterility, 2023, 119(5),815-823.
[3]Chen L., Wang X., Zhang X., Wan H., Su Y., He W., Xie Y.Jing X. Electroacupuncture and Moxibustion-Like Stimulation Relieves Inflammatory Muscle Pain by Activating Local Distinct Layer Somatosensory Afferent Fibers. Front Neurosci, 2021, 15,695152.
[4]Ikeda H., Stark J., Fischer H., Wagner M., Drdla R., Jager T.Sandkuhler J. Synaptic Amplifier of Inflammatory Pain in the Spinal Dorsal Horn. Science, 2006, 312(5780),1659-62.
[5]Guan Y., Borzan J., Meyer R. A.Raja S. N. Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal Mu-Opioid Mechanisms. J Neurosci, 2006, 26(16),4298-307.

Presenting Author

Zhiyun Zhang

Poster Authors

Zhiyun Zhang

Doctor

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences

Lead Author

Qingquan Yu

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences

Lead Author

Yangshuai Su

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences

Lead Author

Xianghong Jing

Lead Author

Topics

  • Models: Chronic Pain - Inflammatory