Activation of spinal ERK signaling pathway contributes to pain-related responses induced by scorpion Buthus martensi Karch venom.
It has been demonstrated that spontaneous nociceptive behaviors, cutaneous hyperalgesia and paw edema can be induced by intraplantar injection of scorpion Buthus martensi Karch (BmK) venom in rats. In the present study, activation of spinal extracellular signal-regulated kinase (ERK) signaling pathway and its contribution to pain-related responses induced by scorpion BmK venom were investigated. It was found that ERK was activated not only in the superficial layers but also in deep layers of L4-L5 spinal cord dorsal horn, which started at 2 min, peaked at 30-60 min and almost disappeared at 4h following intraplantar injection of BmK venom. Intrathecal injection of U0126 (0.1, 1.0 and 10 microg), a widely used specific MAP kinase kinase (MEK) inhibitor, suppressed spontaneous nociceptive responses and reduced primary heat hyperalgesia and bilateral mechanical hyperalgesia induced by BmK venom. In addition, BmK venom-induced spinal c-Fos expression could be inhibited by U0126 dose-dependently. Intrathecal delivery of NMDA receptor antagonist (5R, 10S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]-cyclohepten-5-10-imine hydrogen maleate (MK-801) and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) could partially inhibit activation of spinal ERK induced by BmK venom at 30 min. Thus, activation of ERK in spinal cord dorsal horn, partially mediated by NMDA and non-NMDA receptor, potentially contributes to BmK venom-induced pain-related behaviors.
Pang
Xue-Yan
XY
School of Life Sciences, Shanghai University, Shang-Da Road 99, Shanghai 200444, PR China.
Liu
Tong
T
Jiang
Feng
F
Ji
Yong-Hua
YH
D000818:Animals; D002070:Butadienes; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000494:pharmacology / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D007120:Immunochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012604:Scorpion Venoms; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D012604:Scorpion Venoms; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases