Yu Fan1, Do-Hee Kim1, Young Seob Gwak1, Danbi Ahn1, Yeonhee Ryu2, Suchan Chang1, Bong Hyo Lee1, Kyle B Bills3, Scott C Steffensen4, Chae Ha Yang1, Hee Young Kim5. 1. Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, South Korea. 2. Korean Medicine Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea. 3. Department of Psychology and Neuroscience, Brigham Young University, Provo, UT 84602, United States; Department of Biomedical Sciences, Noorda College of Osteopathic Medicine (P), Provo, UT 84604, United States. 4. Department of Psychology and Neuroscience, Brigham Young University, Provo, UT 84602, United States. 5. Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, South Korea. Electronic address: hykim@dhu.ac.kr.
Abstract
BACKGROUND: Acupuncture has been used to treat a wide variety of diseases, disorders, and conditions for more than 2500 years. While the anatomical structures of acupuncture points (or acupoints) are largely unknown, our previous studies have suggested that many acupoints can be identified as cutaneous neurogenic inflammatory spots (neurogenic spots or Neuro-Sps), arising from the release of neuropeptides from activated small diameter sensory afferents at topographically distinct body surfaces due to the convergence of visceral and somatic afferents. In turn, the neuropeptides released during neurogenic inflammation may play important roles in the effects of acupuncture as well as the formation of active acupoints. Thus, the present study has focused on the role of substance P (SP) in acupuncture signal transduction and effects. METHODS: Neuro-Sps were detected by using in vivo fluorescence imaging after intravenous injection of Evans blue dye (EBD) and compared with traditional acupoints. Stimulatory effects of the Neuro-Sps were examined in a rat model of immobilization-induced hypertension (IMH). The roles of increased SP in Neuro-Sps were also investigated by using immunohistochemistry, in vivo single-fiber peripheral nerve recordings, and in vivo midbrain extracellular recordings. RESULTS: Neurogenic inflammation quickly appeared at acupoints on the wrist and was fully developed within 15 min in IMH model. The Neuro-Sps showed an increased release of SP from afferent nerve terminals. Mechanical stimulation of these Neuro-Sps increased cell excitability in the midbrain (rostral ventrolateral medulla) and alleviated the development of hypertension, which was blocked by the local injection of the SP receptor antagonist CP-99994 into Neuro-Sps prior to acupuncture and mimicked by the local injection of capsaicin. Single fiber recordings of peripheral nerves showed that increased SP into the Neuro-Sps elevated the sensitivity of A- and C-fibers in response to acupuncture stimulation. In addition, the discharge rates of spinal wide dynamic response (WDR) neurons significantly increased following SP or acupuncture treatment in Neuro-Sps in normal rats, but decreased following the injection of CP-99994 into Neuro-Sps in IMH rats. CONCLUSIONS: Our findings suggest that SP released during neurogenic inflammation enhances the responses of sensory afferents to the needling of acupoints and triggers acupuncture signaling to generate acupuncture effects.
BACKGROUND:Acupuncture has been used to treat a wide variety of diseases, disorders, and conditions for more than 2500 years. While the anatomical structures of acupuncture points (or acupoints) are largely unknown, our previous studies have suggested that many acupoints can be identified as cutaneous neurogenic inflammatory spots (neurogenic spots or Neuro-Sps), arising from the release of neuropeptides from activated small diameter sensory afferents at topographically distinct body surfaces due to the convergence of visceral and somatic afferents. In turn, the neuropeptides released during neurogenic inflammation may play important roles in the effects of acupuncture as well as the formation of active acupoints. Thus, the present study has focused on the role of substance P (SP) in acupuncture signal transduction and effects. METHODS:Neuro-Sps were detected by using in vivo fluorescence imaging after intravenous injection of Evans blue dye (EBD) and compared with traditional acupoints. Stimulatory effects of the Neuro-Sps were examined in a rat model of immobilization-inducedhypertension (IMH). The roles of increased SP in Neuro-Sps were also investigated by using immunohistochemistry, in vivo single-fiber peripheral nerve recordings, and in vivo midbrain extracellular recordings. RESULTS:Neurogenic inflammation quickly appeared at acupoints on the wrist and was fully developed within 15 min in IMH model. The Neuro-Sps showed an increased release of SP from afferent nerve terminals. Mechanical stimulation of these Neuro-Sps increased cell excitability in the midbrain (rostral ventrolateral medulla) and alleviated the development of hypertension, which was blocked by the local injection of the SP receptor antagonist CP-99994 into Neuro-Sps prior to acupuncture and mimicked by the local injection of capsaicin. Single fiber recordings of peripheral nerves showed that increased SP into the Neuro-Sps elevated the sensitivity of A- and C-fibers in response to acupuncture stimulation. In addition, the discharge rates of spinal wide dynamic response (WDR) neurons significantly increased following SP or acupuncture treatment in Neuro-Sps in normal rats, but decreased following the injection of CP-99994 into Neuro-Sps in IMHrats. CONCLUSIONS: Our findings suggest that SP released during neurogenic inflammation enhances the responses of sensory afferents to the needling of acupoints and triggers acupuncture signaling to generate acupuncture effects.
Authors: Suchan Chang; Yeonhee Ryu; Young Seob Gwak; Nam Jun Kim; Jin Mook Kim; Jun Yeon Lee; Seol Ah Kim; Bong Hyo Lee; Scott C Steffensen; Eun Young Jang; Chae Ha Yang; Hee Young Kim Journal: Sci Rep Date: 2017-07-13 Impact factor: 4.379