Activation of ERK1/2 in the primary injury site is required to maintain melittin-enhanced wind-up of rat spinal wide-dynamic-range neurons.
Peripheral modulation of wind-up enhancement induced by peripheral tissue injury is investigated in rat spinal wide-dynamic-range (WDR) neurons. After subcutaneous (s.c.) injection of melittin, a pain-related peptidergic component separated from bee venom, the responsiveness of spinal cord WDR neuron to repeated suprathreshold (1.5T, the intensity threshold) electrical stimuli is enhanced. Comparing with the less effects on early response (0-100 ms), melittin significantly increases late response (100 ms to the next stimulus artifact) and after-discharge (starting from 2s after the last stimulus artifact) with 189% and 546%, respectively. Peripheral administration of a specific MEK inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis-[o-aminophenylmercapto] butadiene (U0126, 1 microg) gradually suppresses, but not completely blocks melittin-enhanced wind-up to the similar level of baseline. The inhibitions of U0126 are mainly on late response and after-discharge with 49% and 65%, respectively. Peripheral administration of three doses of U0126 (0.1, 1, 10 microg) has no effects on melittin-induced local paw edema regardless of either pre- or post-treatment of the drug. We conclude that peripheral ERKs pathway in the primary injury site is required to maintain melittin-enhanced wind-up of rat spinal cord wide-dynamic-range neurons.
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
Yao-Qing
YQ
Yu
Feng
F
Zhao
Jun
J
Chen
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005528:Foot / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D008555:Melitten / Q000633:toxicity*; D008839:Microelectrodes; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000008:administration & dosage; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D008555:Melitten; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3