Targeting voltage-gated calcium channels for neuropathic pain management

Voltage-gated calcium channels (VGCC) play obligatory roles in diverse physiological functions. Pathological conditions leading to changes in their biophysical properties and expression levels may cause malfunctions of VGCC-mediated activities, resulting in disease states. It is believed that changes in VGCC properties under pain-inducing conditions may play a causal role in the development of chronic pain, including nerve injury-induced pain or neuropathic pain. For the past several decades, preclinical and clinical research in developing VGCC blockers or modulators for chronic pain management has been fruitful, leading to some U.S. Food and Drug Administration-approved drugs currently available for chronic pain management. However, their efficacy in pain relief is limited in some patients, and their long-term use is limited by their side-effect profiles. Certainly, there is room for improvement in developing more subtype-specific VGCC blockers or modulators for chronic pain conditions. In this review, we summarized the most recent preclinical and clinical studies related to chronic pain medications acting on the VGCC. We also included clinical trials aiming to expand the application of approved VGCC drugs to different pain states derived from various pathological conditions, as well as drug combination therapies trying to improve the efficacies and side-effect profiles of current pain medications.