On October 10th, the Journal of Neuroscience published an article from ION entitled “Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity”. This work was done by graduate students Bo Duan with Long-Jun Wu and colleagues under the supervision of Prof. Tian-Le Xu.

Development of chronic pain involves alterations in peripheral nociceptors as well as elevated neuronal activity in multiple regions of the central nervous system. Duan and colleagues identify the Ca2+-permeable, homomeric ASIC1a channels as the predominant ASIC in rat spinal dorsal horn (SDH) neurons and show that downregulation of ASIC1a by local rat spinal infusion with specific inhibitors or antisense oligonucleotides markedly attenuated complete Freund’s adjuvant (CFA)-induced thermal and mechanical hypersensitivity. Moreover, in vivo electrophysiological recording showed that the elevated ASIC1a activity is required for two forms of central sensitization: C-fiber-induced “wind-up” and CFA-induced hypersensitivity of SDH nociceptive neurons.

These findings reveal that increased ASIC activity in SDH neurons promotes pain by central sensitization. Consequentially, specific blockade of Ca2+-permeable ASIC1a channels will likely have antinociceptive effect by reducing or preventing the development of inflammation-induced central sensitization.