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      Modulation of visceral pain by brain nuclei and brain circuits and the role of acupuncture: a narrative review

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          Abstract

          Visceral pain is a complex and heterogeneous pain condition that is often associated with pain-related negative emotional states, including anxiety and depression, and can exert serious effects on a patient’s physical and mental health. According to modeling stimulation protocols, the current animal models of visceral pain mainly include the mechanical dilatation model, the ischemic model, and the inflammatory model. Acupuncture can exert analgesic effects by integrating and interacting input signals from acupuncture points and the sites of pain in the central nervous system. The brain nuclei involved in regulating visceral pain mainly include the nucleus of the solitary tract, parabrachial nucleus (PBN), locus coeruleus (LC), rostral ventromedial medulla (RVM), anterior cingulate cortex (ACC), paraventricular nucleus (PVN), and the amygdala. The neural circuits involved are PBN-amygdala, LC-RVM, amygdala-insula, ACC-amygdala, claustrum-ACC, bed nucleus of the stria terminalis-PVN and the PVN-ventral lateral septum circuit. Signals generated by acupuncture can modulate the central structures and interconnected neural circuits of multiple brain regions, including the medulla oblongata, cerebral cortex, thalamus, and hypothalamus. This analgesic process also involves the participation of various neurotransmitters and/or receptors, such as 5-hydroxytryptamine, glutamate, and enkephalin. In addition, acupuncture can regulate visceral pain by influencing functional connections between different brain regions and regulating glucose metabolism. However, there are still some limitations in the research efforts focusing on the specific brain mechanisms associated with the effects of acupuncture on the alleviation of visceral pain. Further animal experiments and clinical studies are now needed to improve our understanding of this area.

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          Most cited references115

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          Structure and Function of the Human Insula.

          The insular cortex, or "Island of Reil," is hidden deep within the lateral sulcus of the brain. Subdivisions within the insula have been identified on the basis of cytoarchitectonics, sulcal landmarks, and connectivity. Depending on the parcellation technique used, the insula can be divided into anywhere between 2 and 13 distinct subdivisions. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognition. Here, we provide a concise summary of known structural and functional features of the human insular cortex with a focus on lesion case studies and recent neuroimaging evidence for considerable functional heterogeneity of this brain region.
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            The Parabrachial Nucleus: CGRP Neurons Function as a General Alarm

            The parabrachial nucleus (PBN), which is located in the pons and dissected by one of the major cerebellar output tracks, is known to relay sensory information (visceral malaise, taste, temperature, pain, itch) to forebrain structures including the thalamus, hypothalamus and extended amygdala. The availability of mouse lines expressing Cre-recombinase selectively in subsets of PBN neurons and of Cre-dependent viruses that allow circuit mapping and manipulation of neuron function is beginning to reveal the connectivity and functions of PBN’s component neurons. This review focuses on the PBN neurons that express calcitonin gene-related protein (CGRP PBN ) that play a major role in regulating appetite and transmitting real or potential threat signals to the extended amygdala. The functions of other specific PBN neuronal populations are also discussed. This review aims to encourage investigation of the numerous unanswered questions that are becoming accessible.
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              The amygdala between sensation and affect: a role in pain

              The amygdala is a structure of the temporal lobe thought to be involved in assigning emotional significance to environmental information and triggering adapted physiological, behavioral and affective responses. A large body of literature in animals and human implicates the amygdala in fear. Pain having a strong affective and emotional dimension, the amygdala, especially its central nucleus (CeA), has also emerged in the last twenty years as key element of the pain matrix. The CeA receives multiple nociceptive information from the brainstem, as well as highly processed polymodal information from the thalamus and the cerebral cortex. It also possesses the connections that allow influencing most of the descending pain control systems as well as higher centers involved in emotional, affective and cognitive functions. Preclinical studies indicate that the integration of nociceptive inputs in the CeA only marginally contributes to sensory-discriminative components of pain, but rather contributes to associated behavior and affective responses. The CeA doesn’t have a major influence on responses to acute nociception in basal condition, but it induces hypoalgesia during aversive situation, such as stress or fear. On the contrary, during persistent pain states (inflammatory, visceral, neuropathic), a long-lasting functional plasticity of CeA activity contributes to an enhancement of the pain experience, including hyperalgesia, aversive behavioral reactions and affective anxiety-like states.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                01 November 2023
                2023
                : 17
                : 1243232
                Affiliations
                [1] 1College of Acupuncture and Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine , Ji’nan, China
                [2] 2First Clinical Medicine College, Shandong University of Traditional Chinese Medicine , Ji’nan, China
                [3] 3External Treatment Center of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine , Ji’nan, China
                [4] 4International Office, Shandong University of Traditional Chinese Medicine , Ji’nan, China
                Author notes

                Edited by: Man Li, Huazhong University of Science and Technology, China

                Reviewed by: Yangshuai Su, China Academy of Chinese Medical Sciences, China; Kun Liu, CACMS, China

                *Correspondence: Zhaofeng Li, qdlzfcmd@ 123456126.com ; Mingyao Hao, haomingyao@ 123456yeah.net

                These authors have contributed equally to this work

                Article
                10.3389/fnins.2023.1243232
                10646320
                38027491
                63907ab0-351d-4dd2-89f8-a29f4dac211a
                Copyright © 2023 Dou, Su, Zhou, Mi, Xu, Zhou, Sun, Liu, Hao and Li.

                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
                : 20 June 2023
                : 17 October 2023
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 115, Pages: 14, Words: 14269
                Funding
                Funded by: National Key R&D Program of China
                Award ID: 2022YFC3500705
                Funded by: Acupoint-Viscera Correlation Study Youth Scientific Research Innovation Team, Shandong University of Traditional Chinese Medicine
                Award ID: 22202110
                Funded by: Meridian (Acupoint)—Viscera Regulation and Application Scientific Research Innovation Team, Shandong University of Traditional Chinese Medicine
                Award ID: 220315
                Funded by: SRT Project of Shandong University of Traditional Chinese Medicine
                Award ID: 2023016
                This article was supported by the National Key R&D Program of China (No. 2022YFC3500705); Acupoint-Viscera Correlation Study Youth Scientific Research Innovation Team, Shandong University of Traditional Chinese Medicine (22202110); Meridian (Acupoint)—Viscera Regulation and Application Scientific Research Innovation Team, Shandong University of Traditional Chinese Medicine (220315); SRT Project of Shandong University of Traditional Chinese Medicine (2023016).
                Categories
                Neuroscience
                Review
                Custom metadata
                Perception Science

                Neurosciences
                visceral pain,brain nuclei,brain circuit,acupuncture,analgesia
                Neurosciences
                visceral pain, brain nuclei, brain circuit, acupuncture, analgesia

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