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Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats.
World J Gastroenterol. 2017 Sep 14; 23(34):6220-6230.WJ

Abstract

AIM

To investigate the effects of herb-partitioned moxibustion (HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase (MEK)1, extracellular signal-regulated kinase (ERK)1/2 and cAMP response element binding protein (CREB) in spinal cord of rats with chronic inflammatory visceral pain (CIVP), and to explore the central mechanism of HPM in treating CIVP.

METHODS

Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide (DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu (ST25) and Qihai (CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor (p)MEK1, pERK1/2 and pCREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB mRNA in rat spinal cord were detected using real-time polymerase chain reaction.

RESULTS

Compared with the normal group, the AWR scores were increased significantly (P < 0.01) and the MWT and TWL scores were decreased significantly (P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups (P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly (P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups (P < 0.01 or < 0.05). Compared with the model group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05).

CONCLUSION

HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and mRNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.

Authors+Show Affiliations

Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Huangpu Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200010, China.Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China.Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan Province, China.Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China.Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China.Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China.Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China.Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28974888

Citation

Li, Zhi-Yuan, et al. "Moxibustion Eases Chronic Inflammatory Visceral Pain Through Regulating MEK, ERK and CREB in Rats." World Journal of Gastroenterology, vol. 23, no. 34, 2017, pp. 6220-6230.
Li ZY, Huang Y, Yang YT, et al. Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats. World J Gastroenterol. 2017;23(34):6220-6230.
Li, Z. Y., Huang, Y., Yang, Y. T., Zhang, D., Zhao, Y., Hong, J., Liu, J., Wu, L. J., Zhang, C. H., Wu, H. G., Zhang, J., & Ma, X. P. (2017). Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats. World Journal of Gastroenterology, 23(34), 6220-6230. https://doi.org/10.3748/wjg.v23.i34.6220
Li ZY, et al. Moxibustion Eases Chronic Inflammatory Visceral Pain Through Regulating MEK, ERK and CREB in Rats. World J Gastroenterol. 2017 Sep 14;23(34):6220-6230. PubMed PMID: 28974888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats. AU - Li,Zhi-Yuan, AU - Huang,Yan, AU - Yang,Yan-Ting, AU - Zhang,Dan, AU - Zhao,Yan, AU - Hong,Jue, AU - Liu,Jie, AU - Wu,Li-Jie, AU - Zhang,Cui-Hong, AU - Wu,Huan-Gan, AU - Zhang,Ji, AU - Ma,Xiao-Peng, PY - 2017/02/22/received PY - 2017/07/07/revised PY - 2017/08/08/accepted PY - 2017/10/5/entrez PY - 2017/10/5/pubmed PY - 2018/6/1/medline KW - Analgesia KW - Chronic inflammatory visceral pain KW - Extracellular signal-regulated kinase KW - Herb-partitioned moxibustion KW - MEK KW - Pain behavior KW - Signaling pathway KW - cAMP response element binding protein SP - 6220 EP - 6230 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 23 IS - 34 N2 - AIM: To investigate the effects of herb-partitioned moxibustion (HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase (MEK)1, extracellular signal-regulated kinase (ERK)1/2 and cAMP response element binding protein (CREB) in spinal cord of rats with chronic inflammatory visceral pain (CIVP), and to explore the central mechanism of HPM in treating CIVP. METHODS: Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide (DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu (ST25) and Qihai (CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor (p)MEK1, pERK1/2 and pCREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB mRNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS: Compared with the normal group, the AWR scores were increased significantly (P < 0.01) and the MWT and TWL scores were decreased significantly (P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups (P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly (P < 0.01) and the MWT and TWL scores were increased significantly (P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups (P < 0.01 or < 0.05). Compared with the model group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups (P < 0.01 or < 0.05). CONCLUSION: HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and mRNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/28974888/Moxibustion_eases_chronic_inflammatory_visceral_pain_through_regulating_MEK_ERK_and_CREB_in_rats_ L2 - http://www.wjgnet.com/1007-9327/full/v23/i34/6220.htm DB - PRIME DP - Unbound Medicine ER -