Activation of spinal extracellular signaling-regulated kinases by intraplantar melittin injection.
Intraplantar injection of melittin, a major toxic peptide of whole bee venom, has been proved to cause alteration in both behavioral and spinal neuronal responses in rats. To see whether extracellular signaling-regulated kinases (ERK) in the spinal cord dorsal horn are activated and involved in induction and maintenance of persistent ongoing nociception, pain hypersensitivity and inflammation, three doses of U0126 (1,4-diamino-2,3-dicyano-1, 4-bis-[o-aminophenylmercapto]butadiene), a widely used specific MAP kinase kinase (MEK) inhibitor, were administered through chronic intrathecal catheterization prior to or after intraplantar injection of melittin. We found that: (1) the induction of melittin-induced persistent spontaneous nociception (PSN), mechanical and heat hypersensitivity could be suppressed by U0126 in a dose-related manner; (2) specific inhibition of ERK pathway suppressed the maintenance of melittin-induced PSN and heat hypersensitivity, while established mechanical hypersensitivity could not be reversed; and (3) intrathecal administration of U0126 had no effects on peripheral inflammation induced by melittin. This result suggests that spinal ERK pathway might be a common factor involved in inducing and maintaining pathophysiological processes of ongoing pain and heat hyperalgesia, while the role of ERK pathway in generation of the mechanical hypersensitivity is not consistent and remains to be further clarified.
Yu
Yao-Qing
YQ
Pain Research Center, Institute of Neuroscience, Fourth Military Medical University, 17 West Chang-le Road, Xi'an 710032, PR China.
Chen
Jun
J
D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000008:administration & dosage* / Q000187:drug effects*; D005528:Foot; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology*; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D008555:Melitten / Q000008:administration & dosage*; D009570:Nitriles / Q000008:administration & dosage; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D008555:Melitten; D048049:Extracellular Signal-Regulated MAP Kinases