The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain

Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the alpha 2 delta subunit. The alpha 2 delta subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the alpha 2 delta subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The alpha 2 delta subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target alpha 2 delta subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the alpha 2 delta subunit in perceiving and modulating NP.