Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia
Xiang Cui1 • Guang Sun1,2 • Honglei Cao3 • Qun Liu4 • Kun Liu1 • Shuya Wang1 • Bing Zhu1 • Xinyan Gao1
1 Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China
2 Research Center of Traditional Chinese Medicine, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin 130021, China
3 Department of Cardiology, Jining No. 1 People’s Hospital, Jining 272100, Shandong, China
4 Department of Needling Manipulation, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China
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.
Keywords
Sympathetic-sensory coupling; Neuromodulation; Referred pain; a2 adrenoceptor; Cardioprotectio
