title: Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission.
abstract: The brainstem is well recognized as a critical site for integrating descending modulatory systems that both inhibit and facilitate pain at the level of the spinal cord. The cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) distributes and localizes in the ventral periaqueductal central gray of the brainstem. Although emerging lines of evidence suggest that the CSF-contacting nucleus may be closely linked to transduction and regulation of pain signals, the definitive role of the CSF-contacting nucleus in pain modulation remains poorly understood. In the present study, we determined the role of the CSF-contacting nucleus in rat nocifensive behaviors after persistent pain by targeted ablation of the CSF-contacting nucleus in the brainstem using the cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. Compared with CB/SAP, CB-SAP induced complete ablation of the CSF-contacting nucleus, and the CB-SAP-treated rats showed hypersensitivity in responses to acute nociceptive stimulation, and exacerbated spontaneous nocifensive responses induced by formalin, thermal hyperalgesia and mechanical allodynia induced by plantar incision. Furthermore, immunohistochemical experiments showed that the CSF-contacting nucleus was a cluster of 5-HT-containing neurons in the brainstem, and the spinal projection of serotonergic axons originating from the CSF-contacting nucleus constituted the descending 5-HT pathway to the spinal cord. CB-SAP induced significant downregulation of 5-HT in the spinal dorsal horn, and intrathecal injection of 5-HT significantly reversed hypersensitivity in responses to acute nociceptive stimulation in the CB-SAP-treated rats. These results indicate that the CSF-contacting nucleus 5-HT pathway is an important component of the endogenous descending inhibitory system in the control of spinal nociceptive transmission.
authors.affiliation: Department of Anesthesiology, The First Clinical College, China Medical University, Shenyang 110001, Liaoning Province, PR China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Department of Anesthesiology, The First Clinical College, China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Department of Anesthesiology, The First Clinical College, China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Yan
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Department of Anesthesiology, The First Clinical College, China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Jing-Qiu
authors.initials: JQ
authors.lastname: Wei
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Tiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Cui-Jie
authors.initials: CJ
authors.lastname: Shao
authors.affiliation: School of Nursing, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Xian-Fu
authors.initials: XF
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China.
authors.forename: Hai-Lei
authors.initials: HL
authors.lastname: Ding
authors.affiliation: Department of Anesthesiology, The First Clinical College, China Medical University, Shenyang 110001, Liaoning Province, PR China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, PR China. Electronic address: licaizhang001@163.com.
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000473:pathology*; D002555:Cerebrospinal Fluid; D002772:Cholera Toxin; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D010146:Pain / Q000209:etiology / Q000473:pathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D054789:Ribosome Inactivating Proteins, Type 1; D005557:Formaldehyde; D012701:Serotonin; D002772:Cholera Toxin; D000076985:Saporins
keywords: Brainstem; Cerebrospinal fluid-contacting nucleus; Descending inhibition; Descending serotonergic (5-HT) system; Pain