title: The effects of G-protein and protein kinase inhibitors on the behavioral responses of rats to intradermal injection of capsaicin.
abstract: This study was designed to assess the role of G-proteins and protein kinases in the spinal cord in the behavioral manifestations induced by intradermal injection of capsaicin in rats. A microdialysis fiber was implanted in the spinal cord dorsal horn for administration of G-protein and protein kinase inhibitors to decipher the role of signal transduction cascades in mechanical allodynia induced by intradermal injection of capsaicin. Animals were tested for responses to graded mechanical stimuli using von Frey filaments and for responses to radiant heat stimuli outside the area of injection. The present study demonstrated that intradermal injection of capsaicin results in changes consistent with secondary mechanical allodynia without secondary heat hyperalgesia. Infusion of a G-protein inhibitor (GDP-beta-S), a general protein kinase inhibitor (H7), or selective inhibitors of protein kinase C (NPC15437), protein kinase A (H89), or protein kinase G (KT5823) into the spinal cord dorsal horn reversed the mechanical allodynia induced by intradermal injection of capsaicin in a dose-dependent manner by increasing the threshold to mechanical stimulation towards baseline. This suggests that multiple signal transduction pathways in the spinal cord are involved in the secondary allodynia that occurs following activation of C-fiber afferents by capsaicin.
authors.affiliation: Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Sluka
authors.forename: W D
authors.initials: WD
authors.lastname: Willis
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000008:administration & dosage; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D007271:Injections, Intradermal; D008297:Male; D017551:Microdialysis; D010146:Pain / Q000139:chemically induced / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D002211:Capsaicin