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      Electroacupuncture-Related Metabolic Brain Connectivity in Neuropathic Pain due to Brachial Plexus Avulsion Injury in Rats

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          Abstract

          Objective: The present study aimed to investigate the analgesic effect of electroacupuncture (EA) in neuropathic pain due to brachial plexus avulsion injury (BPAI) and related changes in the metabolic brain connectivity.

          Methods: Neuropathic pain model due to BPAI was established in adult female Sprague–Dawley rats. EA stimulations (2/15 Hz, 30 min/day, 5-day intervention followed by 2-day rest in each session) were applied to the fifth–seventh cervical “Jiaji” acupoints on the noninjured side from 1st to 12th weeks following BPAI (EA group, n = 8). Three control groups included sham EA (nonelectrical acupuncture applied to 3 mm lateral to the real “Jiaji” acupoints), BPAI-only, and normal rats (no particular intervention; eight rats in each group). Thermal withdrawal latency (TWL) of the noninjured forepaw was regularly tested to evaluate the threshold of thermalgesia. Small animal [fluorine-18]-fluoro-2-deoxy- D-glucose ( 18F-FDG) PET/CT scans of brain were conducted at the end of 4th, 12th, and 16th weeks to explore metabolic alterations of brain.

          Results: In the EA group, the TWL of the noninjured forepaw significantly decreased following BPAI and then increased following EA stimulation, compared with sham EA ( P < 0.001). The metabolic brain connectivity among somatosensory cortex (SC), motor cortex (MC), caudate putamen (Cpu), and dorsolateral thalamus (DLT) in bilateral hemispheres decreased throughout the 16 weeks’ observation in the BPAI-only group, compared with the normal rats ( P < 0.05). In the EA group, the strength of connectivity among the above regions were found to be increased at the end of 4th week following BPAI modeling, decreased at 12th week, and then increased again at 16th week ( P < 0.05). The changes in metabolic connectivity were uncharacteristic and dispersed in the sham EA group.

          Conclusion: The study revealed long-term and extensive changes of metabolic brain connectivity in EA-treated BPAI-induced neuropathic pain rats. Bilateral sensorimotor and pain-related brain regions were mainly involved in this process. It indicated that modulation of brain metabolic connectivity might be an important mechanism of analgesic effect in EA stimulation for the treatment of neuropathic pain.

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          Neuropathic pain: mechanisms and their clinical implications.

          Jianren Mao, Joshua Cohen (2013)
          Neuropathic pain can develop after nerve injury, when deleterious changes occur in injured neurons and along nociceptive and descending modulatory pathways in the central nervous system. The myriad neurotransmitters and other substances involved in the development and maintenance of neuropathic pain also play a part in other neurobiological disorders. This might partly explain the high comorbidity rates for chronic pain, sleep disorders, and psychological conditions such as depression, and why drugs that are effective for one condition may benefit others. Neuropathic pain can be distinguished from non-neuropathic pain by two factors. Firstly, in neuropathic pain there is no transduction (conversion of a nociceptive stimulus into an electrical impulse). Secondly, the prognosis is worse: injury to major nerves is more likely than injury to non-nervous tissue to result in chronic pain. In addition, neuropathic pain tends to be more refractory than non-neuropathic pain to conventional analgesics, such as non-steroidal anti-inflammatory drugs and opioids. However, because of the considerable overlap between neuropathic and nociceptive pain in terms of mechanisms and treatment modalities, it might be more constructive to view these entities as different points on the same continuum. This review focuses on the mechanisms of neuropathic pain, with special emphasis on clinical implications.
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            A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI.

            Torsten Reese, Charles Watson, Alessandro Gozzi … (2006)
            We describe a stereotaxic rat brain MRI template set with a co-registered digital anatomical atlas and illustrate its application to the analysis of a pharmacological MRI (phMRI) study of apomorphine. The template set includes anatomical images and tissue class probability maps for brain parenchyma and cerebrospinal fluid (CSF). These facilitate the use of standard fMRI software for spatial normalisation and tissue segmentation of rat brain data. A volumetric reconstruction of the Paxinos and Watson rat brain atlas is also co-localised with the template, enabling the atlas structure and stereotaxic coordinates corresponding to a feature within a statistical map to be interactively reported, facilitating the localisation of functional effects. Moreover, voxels falling within selected brain structures can be combined to define anatomically based 3D volumes of interest (VOIs), free of operator bias. As many atlas structures are small relative to the typical resolution of phMRI studies, a mechanism for defining composite structures as agglomerations of individual atlas structures is also described. This provides a simple and robust means of interrogating structures that are otherwise difficult to delineate and an objective framework for comparing and classifying compounds based on an anatomical profile of their activity. These developments allow a closer alignment of pre-clinical and clinical analysis techniques.
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              Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury.

              Maria Soler, Hatice Kumru, Raul Pelayo … (2010)
              The aim of this study was to evaluate the analgesic effect of transcranial direct current stimulation of the motor cortex and techniques of visual illusion, applied isolated or combined, in patients with neuropathic pain following spinal cord injury. In a sham controlled, double-blind, parallel group design, 39 patients were randomized into four groups receiving transcranial direct current stimulation with walking visual illusion or with control illusion and sham stimulation with visual illusion or with control illusion. For transcranial direct current stimulation, the anode was placed over the primary motor cortex. Each patient received ten treatment sessions during two consecutive weeks. Clinical assessment was performed before, after the last day of treatment, after 2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain Inventory. The combination of transcranial direct current stimulation and visual illusion reduced the intensity of neuropathic pain significantly more than any of the single interventions. Patients receiving transcranial direct current stimulation and visual illusion experienced a significant improvement in all pain subtypes, while patients in the transcranial direct current stimulation group showed improvement in continuous and paroxysmal pain, and those in the visual illusion group improved only in continuous pain and dysaesthesias. At 12 weeks after treatment, the combined treatment group still presented significant improvement on the overall pain intensity perception, whereas no improvements were reported in the other three groups. Our results demonstrate that transcranial direct current stimulation and visual illusion can be effective in the management of neuropathic pain following spinal cord injury, with minimal side effects and with good tolerability.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Neural Circuits
                Journal ID (iso-abbrev): Front Neural Circuits
                Journal ID (publisher-id): Front. Neural Circuits
                Title: Frontiers in Neural Circuits
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1662-5110
                Publication date (Electronic): 17 June 2020
                Publication date Collection: 2020
                Volume: 14
                Electronic Location Identifier: 35
                Affiliations
                [1] 1Shanghai Eighth People Hospital , Shanghai, China
                [2] 2Department of Traumatology and Orthopedics, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [3] 3School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [4] 4Department of Orthopedics, Guanghua Hospital of Integrative Chinese and Western Medicine , Shanghai, China
                Author notes

                Edited by: Ti-Fei Yuan, Shanghai Jiao Tong University, China

                Reviewed by: Sangma Xie, Hangzhou Dianzi University, China; Lijuan Ao, Kunming Medical University, China

                *Correspondence: Jian-Guang Xu xjg@ 123456shutcm.edu.cn

                †These authors have contributed equally to this work

                Article
                DOI: 10.3389/fncir.2020.00035
                PMC ID: 7313422
                PubMed ID: 32174815
                SO-VID: b5b541fc-2344-4dda-8794-636a671a4f04
                Copyright © Copyright © 2020 Hou, Zheng, Hua, Huo, Shen and Xu.
                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 : 19 March 2020
                Date accepted : 12 May 2020
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 63, Pages: 11, Words: 7282
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81802249, 81871836
                Funded by: Shanghai Municipal Health and Family Planning Commission 10.13039/501100014175
                Award ID: 2018YQ02
                Categories
                Subject: Neuroscience
                Subject: Original Research

                ScienceOpen disciplines: Neurosciences
                Keywords: neuropathic pain,brachial plexus avulsion injury,electroacupuncture,thermal withdrawal latency,metabolic connectivity
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: neuropathic pain, brachial plexus avulsion injury, electroacupuncture, thermal withdrawal latency, metabolic connectivity

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