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A role for protein kinase intracellular messengers in substance P- and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro
Article first published online: 20 DEC 2001
European Journal of Neuroscience
Volume 14, Issue 3, pages 426–434, August 2001
How to Cite
Badie-Mahdavi, H., Worsley, M. A., Ackley, M. A., Asghar, A. U. R., Slack, J. R. and King, A. E. (2001), A role for protein kinase intracellular messengers in substance P- and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro. European Journal of Neuroscience, 14: 426–434. doi: 10.1046/j.0953-816x.2001.01656.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received 9 April 2001; revised 29 May 2001, accepted 4 June 2001
Expression of the inducible transcription factor Fos in the spinal dorsal horn in vivo is associated with nociceptive afferent activation, but the underlying stimulation-transcription pathway is less clear. This in vitro spinal cord study concerns the role of protein kinase A and C second messengers in substance P receptor (NK1R)-mediated or nociceptive afferent-evoked neuronal excitation and Fos expression. Nociceptive afferent (dorsal root) stimulation of isolated spinal cords (10–14 day old rats) evoked a ‘prolonged’ excitatory polysynaptic potential (DR-EPSP) that was attenuated (P < 0.05) by: the protein kinase A inhibitor, Rp-cAMP; the protein kinase C inhibitor, bisindolymaleimide I; and the selective NK1R antagonist, GR82334. Neuronal excitations induced by the NK1R agonist [Sar9,Met(O2)11]-SP were attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. Effects of the protein kinase A and C inhibitors on the DR-EPSP or the [Sar9,Met(O2)11]-SP-induced depolarization were nonadditive, suggesting convergence of these intracellular signalling pathways onto a common final target. Nociceptor afferent-induced Fos, detected by immunohistochemistry in superficial and deep dorsal horn laminae, was attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. In spinal cords pretreated with TTX to eliminate indirect neuronal activation, [Sar9,Met(O2)11]-SP (1–20 µm) elicited a dose-related expression of Fos that was reduced by Rp-cAMP, bisindolymaleimide I and GR82334. The effects of these inhibitors were most pronounced in the deep laminae. These data support a causal relationship between protein kinase A- or C-dependent signal transduction, nociceptive afferent- or NK1R-induced neuronal excitation and Fos expression in dorsal horn. Implications for short- versus long-term modulation of nociceptive circuitry are discussed.