Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System
Electroacupuncture (EA) has been used for treating visceral hypersensitivity (VH). However, the underlying molecular mechanism remains unclear. This study was aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA attenuates VH through Janus kinase 2 (JAK2)/signal transduc...
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2017.00644/full |
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| author | Juan Wan Yi Ding Adnan H. Tahir Manoj K. Shah Habibullah Janyaro Xiaojing Li Juming Zhong Vitaly Vodyanoy Mingxing Ding |
| author_facet | Juan Wan Yi Ding Adnan H. Tahir Manoj K. Shah Habibullah Janyaro Xiaojing Li Juming Zhong Vitaly Vodyanoy Mingxing Ding |
| author_sort | Juan Wan |
| collection | DOAJ |
| description | Electroacupuncture (EA) has been used for treating visceral hypersensitivity (VH). However, the underlying molecular mechanism remains unclear. This study was aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA attenuates VH through Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway in the periaqueductal gray (PAG)-the rostral ventromedial medulla (RVM)-the spinal cord dorsal horn (SCDH) axis.Methods: Goats were anesthetized and laparotomized for injecting 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-ethanol solution (30mg TNBS dissolved in 40% ethanol) into the ileal wall to induce VH. EA was treated for 30min from day 7, then every 3 days for six times. VH was assessed by visceromotor response (VMR) and pain behavior response to 20, 40, 60, 80, and 100 mmHg colorectal distension pressures at day 7, 10, 13, 16, 19, and 22. The spinal cord in the eleventh thoracic vertebra and the brain were collected at day 22. The protein and mRNA levels of IL-6, JAK2, and STAT3 in the SCDH were detected with western blot and qPCR, respectively. The distribution of these substances was observed with immunohistochemistry in the ventrolateral PAG (vlPAG), RVM (mainly the nucleus raphe magnus, NRM), SCDH, the nucleus tractus solitaries (NTS) and the dorsal motor nucleus of vagi (DMV).Results: Goats administered with TNBS-ethanol solution showed diarrhea, enhanced VMR and pain behavior response, and increased IL-6, phosphorylated JAK2 and STAT3 (pJAK2 and pSTAT3) in the vlPAG, NRM, NTS and DMV, and their protein and mRNA levels in the SCDH. EA relieved diarrhea, VMR and pain behavior response, decreased IL-6, pJAK2 and pSTAT3 levels in the vlPAG, NRM, SCDH, NTS, and DMV except for pSTAT3 in the DMV, but did not affect mRNA level of these three substances in the SCDH.Conclusion: EA attenuates VH probably through inhibiting JAK2/STAT3 signaling pathway in the PAG-RVM-SCDH axis. |
| first_indexed | 2024-12-10T18:09:12Z |
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| language | English |
| last_indexed | 2024-12-10T18:09:12Z |
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| spelling | doaj.art-9f78e24ae6024da491c61a77ea84246c2022-12-22T01:38:32ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2017-11-011110.3389/fnins.2017.00644302269Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation SystemJuan Wan0Yi Ding1Adnan H. Tahir2Manoj K. Shah3Habibullah Janyaro4Xiaojing Li5Juming Zhong6Vitaly Vodyanoy7Mingxing Ding8Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaDepartment of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL, United StatesDepartment of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL, United StatesDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaElectroacupuncture (EA) has been used for treating visceral hypersensitivity (VH). However, the underlying molecular mechanism remains unclear. This study was aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA attenuates VH through Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway in the periaqueductal gray (PAG)-the rostral ventromedial medulla (RVM)-the spinal cord dorsal horn (SCDH) axis.Methods: Goats were anesthetized and laparotomized for injecting 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-ethanol solution (30mg TNBS dissolved in 40% ethanol) into the ileal wall to induce VH. EA was treated for 30min from day 7, then every 3 days for six times. VH was assessed by visceromotor response (VMR) and pain behavior response to 20, 40, 60, 80, and 100 mmHg colorectal distension pressures at day 7, 10, 13, 16, 19, and 22. The spinal cord in the eleventh thoracic vertebra and the brain were collected at day 22. The protein and mRNA levels of IL-6, JAK2, and STAT3 in the SCDH were detected with western blot and qPCR, respectively. The distribution of these substances was observed with immunohistochemistry in the ventrolateral PAG (vlPAG), RVM (mainly the nucleus raphe magnus, NRM), SCDH, the nucleus tractus solitaries (NTS) and the dorsal motor nucleus of vagi (DMV).Results: Goats administered with TNBS-ethanol solution showed diarrhea, enhanced VMR and pain behavior response, and increased IL-6, phosphorylated JAK2 and STAT3 (pJAK2 and pSTAT3) in the vlPAG, NRM, NTS and DMV, and their protein and mRNA levels in the SCDH. EA relieved diarrhea, VMR and pain behavior response, decreased IL-6, pJAK2 and pSTAT3 levels in the vlPAG, NRM, SCDH, NTS, and DMV except for pSTAT3 in the DMV, but did not affect mRNA level of these three substances in the SCDH.Conclusion: EA attenuates VH probably through inhibiting JAK2/STAT3 signaling pathway in the PAG-RVM-SCDH axis.http://journal.frontiersin.org/article/10.3389/fnins.2017.00644/fullelectroacupuncture (EA)TNBSvisceral hypersensitivity (VH)visceromotor response (VMR)JAK2/STAT3 signaling pathwayPAG-RVM-SCDH axis |
| spellingShingle | Juan Wan Yi Ding Adnan H. Tahir Manoj K. Shah Habibullah Janyaro Xiaojing Li Juming Zhong Vitaly Vodyanoy Mingxing Ding Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System Frontiers in Neuroscience electroacupuncture (EA) TNBS visceral hypersensitivity (VH) visceromotor response (VMR) JAK2/STAT3 signaling pathway PAG-RVM-SCDH axis |
| title | Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System |
| title_full | Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System |
| title_fullStr | Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System |
| title_full_unstemmed | Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System |
| title_short | Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System |
| title_sort | electroacupuncture attenuates visceral hypersensitivity by inhibiting jak2 stat3 signaling pathway in the descending pain modulation system |
| topic | electroacupuncture (EA) TNBS visceral hypersensitivity (VH) visceromotor response (VMR) JAK2/STAT3 signaling pathway PAG-RVM-SCDH axis |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2017.00644/full |
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