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

摘要

Neuropathic pain syndromes affect between 30 and 50% of the world population and represent a significant burden for patients, society, and healthcare systems. Many hypotheses have been formulated about the mechanisms of neuropathic pain among which elevated expression of T-type calcium channels in peripheral nociceptive nerve fibers (so-called “nociceptors”) is seen as a hallmark in several experimental pain models [ ]. Nociceptors have their cell bodies in the dorsal root ganglia (DRG) and express predominantly the Ca 3.2 channel subtype whose primary function is to regulate neuronal firing and synaptic transmission at dorsal horn synapses [ ]. Given these important functions in peripheral sensory neurons, aberrant expression of T-type channels in primary pain fibers comes as a pertinent cellular mechanism of neuropathic pain syndromes. How this up-regulation of T-type channels occurs at a mechanistic level has been the subject of a great deal of research in recent years and several studies pointed to a role of post-translational modification of the channel protein.