Voltage-gated calcium channels in chronic pain: emerging role of alternative splicing.

N- and T-type voltage-gated calcium channels are key established players in chronic pain. Current work suggests that alternative splicing of these channels constitutes an important aspect in the investigation of their roles in the pathogenesis of chronic pain. Recent N-type channel studies describe a nociceptor-enriched alternatively spliced module responsible for voltage-independent G protein modulation and internalization, which is implicated in the control of distinct nociceptive pathways. On the contrary, although a large body of work has demonstrated that peripheral Cav 3.2-encoded T-type currents are involved in several types of chronic pain, little is known with respect to the expression of numerous newly discovered splice variants in specific pain pathways. The elucidation of the new layers of molecular complexity uncovered in N- and T-type channel splice variants and their respective locations and roles in different pain pathways will allow for the development of better therapeutic strategies for the treatment of chronic pain.