Chronic pain is a major therapeutic problem as the current treatment options are unsatisfactory with low
efficacy and deleterious side effects. Voltage-gated Ca2+ channels (VGCCs), which are multi-complex proteins consisting
of α1,β,γ, and α2δ subunits, play an important role in pain signaling. These channels are involved in neurogenic
inflammation, excitability, and neurotransmitter release in nociceptors. It has been previously shown that N-type VGCCs
(Cav2.2) are a major pain target. U.S. FDA approval of three Cav2.2 antagonists, gabapentin, pregabalin, and ziconotide,
for chronic pain underlies the importance of this channel subtype. Also, there has been increasing evidence that L-type
(Cav1.2) or T-type (Cav3.2) VGCCs may be involved in pain signaling and chronic pain. In order to develop novel pain
therapeutics and to understand the role of VGCC subtypes, discovering subtype selective VGCC inhibitors or methods
that selectively target the inhibitor into nociceptors would be essential. This review describes the various VGCC subtype
inhibitors and the potential of utilizing VGCC subtypes as targets of chronic pain. Development of VGCC subtype
inhibitors and targeting them into nociceptors will contribute to a better understanding of the roles of VGCC subtypes in
pain at a spinal level as well as development of a novel class of analgesics for chronic pain.
Keywords: α2δ subunit, Inhibition, L-type Ca2+ channels, N-type Ca2+ channels, Pain, Targeting, T-type Ca2+ channels,
Voltage-gated Ca2+ channels.
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