Inhibition of ERK phosphorylation decreases nociceptive behaviour in monoarthritic rats.
In this study we investigated the role of the activation of the extracellular signal-regulated kinases 1 and 2 (ERK) in chronic inflammatory articular nociception. Monoarthritis was induced in the left ankle of Wistar rats by injection of complete Freund's adjuvant (CFA). Movement of the inflamed joint increased ERK phosphorylation in neurones of the superficial and deep ipislateral dorsal horn laminae of L3-L5 spinal cord segments. Spinal immunoreactivity to phosphoERK was more intense in animals in which the inflammation lasted longer, 7 days or more, than in rats with less time of inflammation. PhosphoERK levels were transient, since 2h after ankle stimulation spinal immunoreaction had almost disappeared. PhosphoERK immunoreactivity was not induced by movement of ankles from non-arthritic control animals, neither in monoarthritic rats in which the inflamed ankle was not stimulated. Intrathecal administration of PD 98059, an inhibitor of ERK phosphorylation, reduced nociceptive behaviour induced by the ankle bend test in monoarthritic rats. The anti-nociceptive effect of PD 98059 was more prominent and in animals with short lasting (4 days) than in animals with longer (14 days) monoarthritis. Taken together, these findings suggest that ERK phosphorylation in spinal cord neurones plays an important role in chronic inflammatory articular pain and that its inhibition may provide significant anti-nociception.
Institute of Histology and Embryology, Faculty of Medicine and IBMC, University of Porto, Alameda Hernâni Monteiro, 4200-319 Porto, Portugal Department of Urology, Faculty of Medicine, University of Porto, Alameda Hernâni Monteiro, 4200-319 Porto, Portugal Neurorestoration Group, Wolfson CARD, King's College, London, UK.
Célia D
CD
Cruz
Fani L
FL
Neto
José
J
Castro-Lopes
Stephen B
SB
McMahon
Francisco
F
Cruz
D000818:Animals; D000842:Ankle / Q000294:innervation; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D005620:Freund's Adjuvant; D007150:Immunohistochemistry / Q000379:methods; D008161:Lumbosacral Region; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology; D013722:Teprotide / Q000494:pharmacology; D013997:Time Factors
D005419:Flavonoids; D005620:Freund's Adjuvant; D013722:Teprotide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010751:Phosphopyruvate Hydratase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one