T-type channels in neuropathic pain - Villain or victim?

摘要

Neuropathic pain syndromes affect between 30 and50% of the world population and representa significant burden for patients, society, and healthcare systems. Many hypotheses have been formulatedabout the mechanisms of neuropathic pain amongwhich elevated expression of T-type calcium channelsin peripheral nociceptive nerve fibers (so-called “nociceptors”) is seen as a hallmark in several experimentalpain models [1]. Nociceptors have their cell bodies inthe dorsal root ganglia (DRG) and express predominantly the Cav3.2 channel subtype whose primaryfunction is to regulate neuronal firing and synaptictransmission at dorsal horn synapses [2]. Given theseimportant functions in peripheral sensory neurons,aberrant expression of T-type channels in primarypain fibers comes as a pertinent cellular mechanismof neuropathic pain syndromes. How this up-regulation of T-type channels occurs at a mechanistic levelhas been the subject of a great deal of research inrecent years and several studies pointed to a role ofpost-translational modification of the channel protein.