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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

      52,235 Monthly downloads/views I 2.832 Impact Factor I 4.5 CiteScore I 1.2 Source Normalized Impact per Paper (SNIP) I 0.655 Scimago Journal & Country Rank (SJR)

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      Central Sensitization-Related Changes in Brain Function Activity in a Rat Endometriosis-Associated Pain Model

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          Abstract

          Background

          Pain sensitization processing in the central nervous system may be related to endometriosis-associated pain in patients. The purpose of this study was to understand the alterations in the abnormal pain response in central brain areas and explore the central sensitization mechanism of endometriosis-associated pain.

          Methods

          An endometriosis model was established in 40 Sprague-Dawley rats, and the rats underwent pain model assessment through behavioral tests. Twenty Sprague-Dawley rats underwent a sham operation as the control group. Thirteen pain rats and 8 control rats received Rs-fMRI examination to explore the brain functional activity areas, and the regional homogeneity (ReHo) method was used to analyze relevant functional signals among the whole brain. The states of neurons and expression of TRPV1 and NMDRA located in the abnormal ReHo signal brain regions were observed using Nissl staining, qRT-PCR and immunohistochemistry.

          Results

          The rats were divided into a pain group and a control group based on the different syndromes and behavioral assessments. We detected significant enhancement of ReHo signals in the anterior cingulate cortex, hippocampus, and thalamus and a reduction in the ReHo values in the basomedial amygdaloid nucleus (BM) and primary motor cortex (M1) in the pain rat group via Rs-fMRI examination. The number of Nissl bodies and apoptotic neurons was increased; moreover, the volume of neurons increased compensatorily in the cingulate cortex, thalamus and hippocampus in the pain group. TRPV1 and NMDRA were overexpressed in apoptotic neurons in the higher ReHo value brain regions in the endometriosis pain group.

          Conclusion

          These findings suggest that in rats with endometriosis-associated pain, ReHo signal enhancement was observed in the cingulate cortex, thalamus and hippocampus, which may be due to the increase in the number of apoptotic neurons or the compensatory increase in the volume of overactive neurons.

          Most cited references44

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          Central mechanisms of pathological pain.

          Rohini Kuner (2010)
          Chronic pain is a major challenge to clinical practice and basic science. The peripheral and central neural networks that mediate nociception show extensive plasticity in pathological disease states. Disease-induced plasticity can occur at both structural and functional levels and is manifest as changes in individual molecules, synapses, cellular function and network activity. Recent work has yielded a better understanding of communication within the neural matrix of physiological pain and has also brought important advances in concepts of injury-induced hyperalgesia and tactile allodynia and how these might contribute to the complex, multidimensional state of chronic pain. This review focuses on the molecular determinants of network plasticity in the central nervous system (CNS) and discusses their relevance to the development of new therapeutic approaches.
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            Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory.

            Ming-Gao Zhao, Hiroki Toyoda, Yong-Seok Lee … (2005)
            Cortical plasticity is thought to be important for the establishment, consolidation, and retrieval of permanent memory. Hippocampal long-term potentiation (LTP), a cellular mechanism of learning and memory, requires the activation of glutamate N-methyl-D-aspartate (NMDA) receptors. In particular, it has been suggested that NR2A-containing NMDA receptors are involved in LTP induction, whereas NR2B-containing receptors are involved in LTD induction in the hippocampus. However, LTP in the prefrontal cortex is less well characterized than in the hippocampus. Here we report that the activation of the NR2B and NR2A subunits of the NMDA receptor is critical for the induction of cingulate LTP, regardless of the induction protocol. Furthermore, pharmacological or genetic blockade of the NR2B subunit in the cingulate cortex impaired the formation of early contextual fear memory. Our results demonstrate that the NR2B subunit of the NMDA receptor in the prefrontal cortex is critically involved in both LTP and contextual memory.
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              An overview of animal models of pain: disease models and outcome measures.

              Michael Dougherty, Philip C. Robinson, Claire Harris … (2013)
              Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience, including reflexive hyperalgesia measures, sensory and affective dimensions of pain, and impact of pain on function and quality of life. In this review, we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes as well as the main behavioral tests for assessing pain in each model. Understanding animal models and outcome measures in animals will assist in translating data from basic science to the clinic. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Pain Res
                Journal ID (iso-abbrev): J Pain Res
                Journal ID (publisher-id): JPR
                Journal ID (pmc): jpainres
                Title: Journal of Pain Research
                Publisher: Dove
                ISSN (Electronic): 1178-7090
                Publication date (Electronic): 13 January 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 95-107
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing, People’s Republic of China
                [2 ]Air Force Medical Center, PLA , Beijing, People’s Republic of China
                [3 ]Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100193, People’s Republic of China
                Author notes
                Correspondence: Jinghe Lang Email langjh@hotmail.com
                Jinhua Leng Email lengjenny@vip.sina.com
                Article
                Publisher ID: 232313
                DOI: 10.2147/JPR.S232313
                PMC ID: 6968808
                PubMed ID: 32021399
                SO-VID: a532c7d4-1be4-4cda-acf1-4dcad9657235
                Copyright © © 2020 Zheng et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 24 September 2019
                Date accepted : 17 December 2019
                Page count
                Figures: 8, Tables: 5, References: 48, Pages: 13
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: endometriosis-associated pain,rat model,behavioral assessment,central sensitization,rs-fmri,regional homogeneity,trpv1,nmdra
                Data availability:
                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: endometriosis-associated pain, rat model, behavioral assessment, central sensitization, rs-fmri, regional homogeneity, trpv1, nmdra

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