title: Activation of ERK signaling in rostral ventromedial medulla is dependent on afferent input from dorsal column pathway and contributes to acetic acid-induced visceral nociception.
abstract: Several lines of evidence from both animal and clinical studies have demonstrated that dorsal column (DC) pathway plays a critical role in visceral pain transmission from the spinal cord to supraspinal center. The descending pain modulation pathway from the rostral ventromedial medulla (RVM) area has been implicated in visceral nociceptive neurotransmission. Previous studies have demonstrated that the multiple protein kinase signaling transduction cascades in the RVM area contribute to the descending facilitation of inflammatory pain and neuropathic pain. However, whether these signaling transduction pathways in the RVM area are triggered by the afferent visceral input from the DC pathway during acute visceral pain remains elusive. Here, we have tested the hypothesis that the afferent visceral stimuli from the DC pathway might induce the activation of extracellular signal-regulated protein kinase (ERK) signaling in the RVM area and contribute to the descending facilitation of neurotransmission in a rat model of visceral pain. Our results showed that acetic acid-induced visceral nociception produced a persistent activation of ERK in the RVM area and a microinjection of a mitogen-activated ERK kinase (MEK) inhibitor, U0126, into the RVM area significantly inhibited the visceral noxious stimulation-induced behaviors in rats. A microinjection of lidocaine into the nucleus gracilis (NG) also inhibited the activation of ERK in the RVM area. The current study indicates that activated ERK signaling pathway in the RVM area is dependent on afferent input from dorsal column pathway and may contribute to acetic acid-induced visceral nociception.
authors.affiliation: Department of Pharmaceutical Science, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kang
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Guo
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Yonggao
authors.initials: Y
authors.lastname: Mu
authors.forename: Anshi
authors.initials: A
authors.lastname: Wu
authors.forename: Yun
authors.initials: Y
authors.lastname: Yue
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D019342:Acetic Acid / Q000633:toxicity*; D000344:Afferent Pathways; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology* / Q000503:physiopathology; D008845:Microinjections; D009570:Nitriles / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014781:Viscera
chemical_list: D000779:Anesthetics, Local; D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D008012:Lidocaine; D048049:Extracellular Signal-Regulated MAP Kinases; D019342:Acetic Acid
keywords: Dorsal column; Rostral ventromedial medulla; Signal transduction; Visceral pain