title: The regulation of sGC on the rat model of neuropathic pain is mediated by 5-HT1ARs and NO/cGMP pathway.
abstract: Inadequate management of neuropathic pain results in poor clinical outcomes and reduces quality of life for the patient all over the world, but intricate interplay between wide variety of the pathophysiological mechanisms involved in the development and progression of neuropathic pain makes it difficult to design effective therapeutic strategies. The present study aims to elucidate the interaction of 5-HT1A receptors (5-HT1ARs), soluble guanylate cyclase (sGC) and NO/cGMP signaling pathway in the development of neuropathic pain. The results showed that after sciatic nerve crush procedure, the protein level of sGC in the spinal cord was greatly increased. The mechanical threshold in rats was significantly enhanced by the sGC inhibitor ODQ and neuronal NO synthase (nNOS) inhibitor SMTC, indicating the role of sGC and nNOS in the process of neuropathic pain. The treatment of NO donors (SNP and SIN-1) and cGMP-selective phosphodiesterase inhibitor (Zaprinast) all significantly decreased the mechanical threshold in rats, but the 5-HT1ARs inhibitor WAY100635 significantly increased the mechanical threshold in rats, demonstrating the role of NO/cGMP pathway and 5-HT1ARs in the development of neuropathic pain. Finally, the protein levels of sGC was greatly increased by SNP and Zaprinast but decreased by WAY100635 and SMTC, showing the regulation of NO/cGMP pathway and 5-HT1ARs on the protein expression of sGC. Taken together, it is suggested that sGC in the spinal cord regulates the neuropathic pain, which is mediated by 5-HT1ARs and NO/cGMP pathway.
authors.affiliation: Department of Anesthesiology, International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200030, China.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Chongqing Cancer Institute/Cancer Hospital Chongqing 400030, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University Shanghai 20080, China.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University Shanghai 20080, China.
authors.forename: Jijian
authors.initials: J
authors.lastname: Zheng
keywords: 5-HT1A receptors; NO/cGMP pathway; Neuropathic pain; neuronal NO synthase; soluble guanylate cyclase