title: Upregulation of spinal NMDA receptors mediates hydrogen sulfide-induced hyperalgesia.
abstract: Hydrogen sulfide (H2S) is an endogenous neurotransmitter that importantly regulates various physiological and pathological events including pain signal transduction. In this study, we investigated the role of spinal NMDA receptors in the nociception induced by intraplantar injection of NaHS, an H2S donor. Intraplantar injection of NaHS into hindpaw significantly decreased the paw withdrawal threshold (PWT) in contralateral hindpaw. However, intraplantar formalin injection did not produce PWT in contralateral hindpaw. Intrathecal injection of methemoglobin, a H2S scavenger, abolished hyperalgesia induced by NaHS. In addition, NaHS-induced hyperalgesia was partly, but significantly, attenuated by intrathecal injection of hydroxylamine, a cystathionine-β-synthase (CBS) inhibitor. RT-PCR and western blotting analysis revealed that NR2B mRNA and protein levels were increased in the spinal dorsal horn, but not in dorsal root ganglion (DRG) in rats subjected to NaHS intraplantar injection. Collectively, these data suggest that peripheral injection of H2S donor causes hyperalgesia through increase in NR2B expression and production of H2S in the spinal cord.
authors.affiliation: Department of Anesthesiology, The Third Hospital of HeBei Medical University, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The Third Hospital of HeBei Medical University, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Department of Physiology, HeBei Medical University, Shijiazhuang, HeBei 050017, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, The Third Hospital of HeBei Medical University, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, The Third Hospital of HeBei Medical University, China.
authors.forename: Yue-Xian
authors.initials: YX
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, The Third Hospital of HeBei Medical University, China. Electronic address: wangxl311@126.com.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000633:toxicity*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D006862:Hydrogen Sulfide
keywords: Dorsal root ganglion; Hydrogen sulfide; Hyperalgesia; NMDA receptor; Pain; Spinal cord