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      Correlated Sensory and Sympathetic Innervation Between the Acupoint BL23 and Kidney in the Rat

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          Abstract

          Objective: To investigate the sensory and sympathetic innervations associated with both acupoint “Shenshu” (BL23) and kidney in the rat for insight into the neuronal correlation between the Back-Shu Point and its corresponding visceral organ.

          Methods: The BL23 and kidney were selected as the representative acupoint and visceral organ in this study, in which their local nerve fibers were examined by using double fluorescent immunohistochemistry with calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH). Meanwhile, their neuronal correlation in the dorsal root ganglia (DRGs), spinal cord, and sympathetic (paravertebral) chain were investigated using a double fluorescent neural tracing technique with Alexa Fluor 488 and 594 conjugates with cholera toxin subunit B (AF488/594-CTB).

          Results: The local tissue of acupoint BL23 and the fibrous capsule of kidney distributed abundantly with CGRP- and TH-positive nerve fibers, corresponding to their sensory and sympathetic innervation. On the other hand, the sensory neurons associated with acupoint BL23 and kidney were labeled with AF488/594-CTB and distributed from thoracic (T) 11 to lumbar (L) 3 DRGs and from T10 to L2 DRGs, respectively, in which some of them in T12-T13 DRGs were simultaneously labeled with both AF488/594-CTB. Also, postganglionic neurons associated with both acupoint BL23 and kidney were found in the sympathetic chain at the same spinal segments but separately labeled with AF488-CTB and AF594-CTB.

          Conclusion: Our study demonstrates the neural characteristics of the acupoint BL23 and kidney in the rat from the perspective of neurochemistry and neural pathways, providing an example for understanding the neuronal correlation between the Back-Shu Points and their corresponding visceral organs. These results suggest that the stimulation of the Back-Shu Points may regulate the activities of the target-organs via the periphery sensory and sympathetic pathways.

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          Calcitonin gene-related peptide: physiology and pathophysiology.

          F Russell, Daniel R King, S-J Smillie … (2014)
          Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.
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            The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

            Smriti Iyengar, Michael Ossipov, Kirk Johnson (2017)
            Abstract Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.
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              Hyperactivation of Sympathetic Nerves Drives Melanocyte Stem Cell Depletion

              Bing Zhang, Sai Ma, Inbal Rachmin … (2020)
              SUMMARY Empirical and anecdotal evidence have associated stress with accelerated hair greying (formation of unpigmented hairs) 1,2 , but the scientific evidence linking the two is scant. Here, we report that acute stress leads to hair greying through fast depletion of melanocyte stem cells (MeSCs). Combining adrenalectomy, denervation, chemogenetics 3,4 , cell ablation, and MeSC-specific adrenergic receptor knockout, we found that stress-induced MeSC loss is independent of immune attack or adrenal stress hormones. Rather, hair greying results from activation of the sympathetic nerves that innervate the MeSC niche. Upon stress, sympathetic nerve activation leads to burst release of the neurotransmitter norepinephrine, which drives quiescent MeSCs into rapid proliferation, followed by differentiation, migration, and permanent depletion from the niche. Transient suppression of MeSC proliferation prevents stress-induced hair greying. Our studies demonstrate that acute stress-induced neuronal activity can drive rapid and permanent loss of somatic stem cells, and illustrate an example in which somatic stem cell maintenance is directly influenced by the overall physiological state of the organism.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Integr Neurosci
                Journal ID (iso-abbrev): Front Integr Neurosci
                Journal ID (publisher-id): Front. Integr. Neurosci.
                Title: Frontiers in Integrative Neuroscience
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1662-5145
                Publication date (Electronic): 11 January 2021
                Publication date Collection: 2020
                Volume: 14
                Electronic Location Identifier: 616778
                Affiliations
                [1] 1Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University , Hangzhou, China
                [2] 2Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences , Beijing, China
                Author notes

                Edited by: Eduardo Weruaga, University of Salamanca, Spain

                Reviewed by: Elias Manjarrez, Meritorious Autonomous University of Puebla, Mexico; Raul Aguilar-Roblero, National Autonomous University of Mexico, Mexico

                *Correspondence: Xianghong Jing jxhtjb@ 123456263.net Wanzhu Bai wanzhubaisy@ 123456hotmail.com
                Article
                DOI: 10.3389/fnint.2020.616778
                PMC ID: 7829193
                PubMed ID: 33505253
                SO-VID: b60d1ac9-e212-481e-b05b-3a82fd01c46a
                Copyright © Copyright © 2021 Zhang, Xu, Wang, Cui, Wu, Zou, Shen, Jing and Bai.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 13 October 2020
                Date accepted : 15 December 2020
                Page count
                Figures: 6, Tables: 0, Equations: 4, References: 62, Pages: 9, Words: 6129
                Categories
                Subject: Neuroscience
                Subject: Original Research

                ScienceOpen disciplines: Neurosciences
                Keywords: kidney,shenshu (bl23),double fluorescent neural tracing technique,sensory neuron,postganglionic neuron
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: kidney, shenshu (bl23), double fluorescent neural tracing technique, sensory neuron, postganglionic neuron

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