Central and peripheral contributions of T-type calcium channels in pain

Chronic pain is a severely debilitating condition that reflects a long-term sensitization of signal transduction in the afferent pain pathway. Among the key players in this pathway are T-type calcium channels, in particular the Ca(v)3.2 isoform. Because of their biophysical characteristics, these channels are ideally suited towards regulating neuronal excitability. Recent evidence suggests that T-type channels contribute to excitability of neurons all along the ascending and descending pain pathways, within primary afferent neurons, spinal dorsal horn neurons, and within pain-processing neurons in the midbrain and cortex. Here we review the contribution of T-type channels to neuronal excitability and function in each of these neuronal populations and how they are dysregulated in chronic pain conditions. Finally, we discuss their molecular pharmacology and the potential role of these channels as therapeutic targets for chronic pain.