• E M Garry, A Delaney, G Blackburn-Munro, T Dickinson, A Moss, I Nakalembe, D C Robertson, R Rosie, P Robberecht, R Mitchell, and S M Fleetwood-Walker.
• Centre for Neuroscience, Division of Veterinary Biomedical Sciences, University of Edinburgh, EH9 1QH, UK.
• Mol. Cell. Neurosci. 2005 Dec 1; 30 (4): 523-37.

AbstractActivation of intracellular signaling pathways involving p38 and p42/44 MAP kinases may contribute importantly to synaptic plasticity underlying spinal neuronal sensitization. Inhibitors of p38 or p42/44 pathways moderately attenuated responses of dorsal horn neurons evoked by mustard oil but not brush and alleviated the behavioral reflex sensitization seen following nerve injury. Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC2 and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha. A VPAC2 receptor agonist enhanced p38 phosphorylation and caused behavioral reflex sensitization in naïve animals that could be blocked by co-administration of p38 inhibitor. Conversely, an NK2 receptor agonist activated p42/44 and caused behavioral sensitization that could be prevented by co-administration of p42/44 inhibitor. Thus, spinal p38 and p42/44 MAP kinases are activated in neuropathic pain states by mechanisms involving VPAC2, NK2, NMDA receptors and glial cytokine production.

55 keywords...

hide…