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Isabelle Decosterd"Douleur neuropathique, composante périphérique et canaux sodiques voltage-dépendants"

Abstract :

Chronic pain, and especially neuropathic pain (NP), is a frequent (prevalence 6.9%) and disabling disorder occurring as a consequence of lesion or disease of the somatosensory system. The pathogenesis of NP involves multiple players; one of the prominent among them is the appearance of a positive shift in the excitability of the peripheral and central nervous system. This peripheral activity is mainly sustained by voltage-gated sodium channels, where Nav1.7 isoform seems to be an important candidate since loss of function mutations reported in the corresponding gene was associated with congenital inability to experience pain. These channels contain an α-subunit (Nav1f), forming the pore of the channel, and β-subunit responsible for the regulation of channel density at the cell membrane. Our laboratory has investigated the dysregualtion of alpha and beta subunits in experimental models of NP and we are now working on the alteration of voltage-gated sodium channels turnover at the plasma membrane related to beta subunits and ubiquitylation. Another part of our research has been devoted to the central changes that are driven by the abnormal peripheral activity. Taken together our results suggest modifying channel turnover may be new therapeutic alternatives and one might consider preventing PNS and CNS alterations in neuropathic pain by blocking the activity at the periphery in combination with other therapeutics.

Selected publications

Berta,T., Poirot,O., Pertin,M., Ji,R.R., Kellenberger,S., and Decosterd,I., Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain, Mol.Cell Neurosci., 37 (2008) 196-208. 

Pertin,M., Ji,R.R., Berta,T., Powell,A.J., Karchewski,L., Tate,S.N., Isom,L.L., Woolf,C.J., Gilliard,N., Spahn,D.R., and Decosterd,I., Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons, J.Neurosci., 25 (2005) 10970-10980.