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      Journal of Pain Research (submit here)

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      Is Open Access

      Moxibustion Eases Chronic Inflammatory Visceral Pain In Rats Via MAPK Signaling Pathway In The Spinal Cord

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          Abstract

          Purpose

          The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP).

          Methods

          A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways.

          Results

          Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P<0.01) under different levels of distending pressure and an increase in MWT and TWL thresholds (all P<0.05). Compared with the normal group, 76 proteins were upregulated while 15 were downregulated, and MAPK signaling pathway was activated in the model group. Compared with the model group, there were 53 downregulated and 38 upregulated proteins in the moxibustion group, and MAPK signaling pathway was inhibited. Fold change (FC)>1.3 or <0.77 was taken as the screening standard to define the differentially expressed proteins. Fifteen differentially expressed proteins upregulated in the model group were downregulated in the moxibustion group. GO analysis showed that the differentially expressed proteins mainly controlled cellular metabolism regulation, transportation, and stress reactions. KEGG analysis revealed that these differentially expressed proteins were mostly involved in the ERK, JNK, and p38 pathways, and the ERK pathway was predominant.

          Conclusion

          Moxibustion mitigates CIVP in rats and inhibits the phosphorylation of proteins in the spinal MAPK signaling pathway. The analgesic effect of moxibustion may be associated with the regulation of the spinal MAPK signaling pathway.

          Most cited references47

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          Hapten-induced model of chronic inflammation and ulceration in the rat colon.

          We have developed a simple and reproducible rat model of chronic colonic inflammation by the intraluminal instillation of a solution containing a "barrier breaker" and a hapten. Administration of the hapten 2,4,6-trinitrobenzenesulfonic acid (5-30 mg) in 0.25 ml of 50% ethanol as the "barrier breaker" produced dose-dependent colonic ulceration and inflammation. At a dose of 30 mg, trinitrobenzenesulfonic acid/ethanol-induced ulceration and marked thickening of the bowel wall persisted for at least 8 wk. Histologically, the inflammatory response included mucosal and submucosal infiltration by polymorphonuclear leukocytes, macrophages, lymphocytes, connective tissue mast cells, and fibroblasts. Granulomas were observed in 57% of the rats killed 3 wk after induction of inflammation. Langhan's-type giant cells were also observed. Segmental ulceration and inflammation were common. The characteristics and relatively long duration of inflammation and ulceration induced in this model afford an opportunity to study the pathophysiology of colonic inflammatory disease in a specifically controlled fashion, and to evaluate new treatments potentially applicable to inflammatory bowel disease in humans.
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            A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development.

            The irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain in the setting of altered perception of viscerosensory stimuli. This so-called visceral hyperalgesia occurs in the absence of detectable organic disease in the peripheral organs and may cause normal or physiologic contractions to be perceived as painful. Although the pathogenesis of IBS remains speculative and is probably multifactorial, a prevailing paradigm is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. Neonatal male Sprague-Dawley rats received either mechanical or chemical colonic irritation between postnatal days 8 and 21 and were tested when they became adults. The abdominal withdrawal reflex and the responses of viscerosensitive neurons were recorded during colon distention. Colon irritation in neonates, but not in adults, results in chronic visceral hypersensitivity, with characteristics of allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology. These results concur largely with observations in patients with IBS, providing a new animal model to study IBS and validating a neurogenic component of functional abdominal pain that encourages novel approaches to health care and research.
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              Acupuncture analgesia: areas of consensus and controversy.

              Sheng Han (2011)
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                07 November 2019
                2019
                : 12
                : 2999-3012
                Affiliations
                [1 ]Yueyang Clinical Medical School, Shanghai University of Traditional Chinese Medicine , Shanghai 201203, People’s Republic of China
                [2 ]Acupuncture and Moxibustion Department, Huangpu District Hospital of Integrated Traditional Chinese and Western Medicine , Shanghai 200010, People’s Republic of China
                [3 ]Laboratory of Acupuncture, Moxibustion, and Immunology, Shanghai Research Institute of Acupuncture and Meridian , Shanghai 200030, People’s Republic of China
                [4 ]Acupuncture and Moxibustion Department, Zhejiang Provincial Hospital of TCM , Hangzhou, Zhejiang 310006, People’s Republic of China
                Author notes
                Correspondence: Xiao-Peng Ma Shanghai Research Institute of Acupuncture and Meridian , No. 650 South Wanping Road, Xuhui District, Shanghai, People’s Republic of ChinaTel +86 021 64690257Fax +86 021 64382181 Email pengpengma@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-0747-8691
                http://orcid.org/0000-0003-1388-4047
                http://orcid.org/0000-0002-9857-818X
                http://orcid.org/0000-0002-0582-3562
                Article
                218588
                10.2147/JPR.S218588
                6844221
                31807057
                fdea6694-a0ba-427f-b886-c70e2dc11ec0
                © 2019 Huang et al.

                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
                : 06 June 2019
                : 09 October 2019
                Page count
                Figures: 5, Tables: 5, References: 56, Pages: 14
                Categories
                Original Research

                Anesthesiology & Pain management
                chronic inflammatory visceral pain,moxibustion,analgesia,spinal cord,mapk signaling pathway

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