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Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia

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Abstract

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8–T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

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Acknowledgments

We are grateful to Dr. Haifa Qiao of Shaanxi University of Chinese Medicine and Dr. Yun Guan of Johns Hopkins University School of Medicine for constructive comments on an earlier version of the manuscript. We thank Dr. Wanzhu Bai, Dongsheng Xu, and Yangshuai Su of the Institute of Acupuncture and Moxibustion of the China Academy of Chinese Medical Sciences for technical assistance. This work was supported by the National Key R&D Program of China (2018YFC1704600) and the National Natural Science Foundation of China (81674085, 81904309).

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Authors and Affiliations

  1. Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Xiang Cui, Guang Sun, Kun Liu, Shuya Wang, Bing Zhu & Xinyan Gao

  2. Research Center of Traditional Chinese Medicine, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130021, China

    Guang Sun

  3. Department of Cardiology, Jining No. 1 People’s Hospital, Jining, 272100, Shandong, China

    Honglei Cao

  4. Department of Needling Manipulation, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Qun Liu

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  1. Xiang Cui
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Cui, X., Sun, G., Cao, H. et al. Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia. Neurosci. Bull. 38, 386–402 (2022). https://doi.org/10.1007/s12264-022-00841-w

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