Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine beta-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity
机构：[1]Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory of Translational Pain Medicine, Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, United States
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alteration of bowel movements. The pathogenesis of visceral hypersensitivity in IBS patients remains largely unknown. Hydrogen sulfide (H2S) is reported to play an important role in development of visceral hyperalgesia. However, the role of H2S at spinal dorsal horn level remains elusive in visceral hypersensitivity. The aim of this study is designed to investigate how H2S takes part in visceral hypersensitivity of adult rats with neonatal colonic inflammation (NCI). Visceral hypersensitivity was induced by neonatal colonic injection of diluted acetic acid. Expression of an endogenous H2S synthesizing enzyme cystathionine beta-synthetase (CBS) was determined by Western blot. Excitability and synaptic transmission of neurons in the substantia gelatinosa (SG) of spinal cord was recorded by patch clamping. Here, we showed that expression of CBS in the spinal dorsal horn was significantly upregulated in NCI rats. The frequency of glutamatergic synaptic activities in SG was markedly enhanced in NCI rats when compared with control rats. Application of NaHS increased the frequency of both spontaneous and miniature excitatory postsynaptic currents of SG neurons in control rats through a presynaptic mechanism. In contrast, application of AOAA, an inhibitor of CBS, dramatically suppressed the frequency of glutamatergic synaptic activities of SG neurons of NCI rats. Importantly, intrathecal injection of AOAA remarkably attenuated visceral hypersensitivity of NCI rats. These results suggest that H2S modulates pain signaling likely through a presynaptic mechanism in SG of spinal dorsal horn, thus providing a potential therapeutic strategy for treatment for chronic visceral pain in patients with IBS.
基金：
This work was supported by grants from National Natural
Science Foundation of China (81230024 and 81471137 to GY-X,
31300909 to YX).
第一作者机构：[1]Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory of Translational Pain Medicine, Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou, China,
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory of Translational Pain Medicine, Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou, China,
推荐引用方式(GB/T 7714)：
Liting Zhao,Ying Xiao,Rui-Xia Weng,et al.Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine beta-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity[J].FRONTIERS IN PHARMACOLOGY.2017,8(OCT):696.doi:10.3389/fphar.2017.00696.
APA：
Liting Zhao,Ying Xiao,Rui-Xia Weng,Xuelian Liu,Ping-An Zhang...&Guang-Yin Xu.(2017).Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine beta-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity.FRONTIERS IN PHARMACOLOGY,8,(OCT)
MLA：
Liting Zhao,et al."Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine beta-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity".FRONTIERS IN PHARMACOLOGY 8..OCT(2017):696
