The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain.

Wenqiang Cui,Xiaowen Yu,Xiangqing Xu,Ting Song,Fei Xu,Hongyun Wu

doi:10.3389/fncel.2021.699731

Abstract

Neuropathic pain is mainly triggered after nerve injury and associated with plasticity of the nociceptive pathway in primary sensory neurons. Currently, the treatment remains a challenge. In order to identify specific therapeutic targets, it is necessary to clarify the underlying mechanisms of neuropathic pain. It is well established that primary sensory neuron sensitization (peripheral sensitization) is one of the main components of neuropathic pain. Calcium channels act as key mediators in peripheral sensitization. As the target of gabapentin, the calcium channel subunit α2δ1 (Cavα2δ1) is a potential entry point in neuropathic pain research. Numerous studies have demonstrated that the upstream and downstream targets of Cavα2δ1 of the peripheral primary neurons, including thrombospondins, N-methyl-D-aspartate receptors, transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid family 1 (TRPV1), and protein kinase C (PKC), are involved in neuropathic pain. Thus, we reviewed and discussed the role of Cavα2δ1 and the associated signaling axis in neuropathic pain conditions.

Highlights

Neuropathic pain is a chronic pain triggered by peripheral nerve injury, postherpetic neuralgia, diabetic neuropathy, and chemotherapeutic agents, such as cisplatin (Colleoni and Sacerdote, 2010)
The mechanical and cold hyperalgesia induced by nerve injury could be mimicked by injecting the Cavα2δ1 overexpression adeno-associated virus (AAV) and be reversed by injecting the AAV of Cavα2δ1 downregulation in trigeminal ganglion (TG) neurons (Cui et al, 2020). These results indicated that the Cavα2δ1 of primary afferent neurons play a vital role in neuropathic pain and that is mainly related to its regulation of Ca2+ inflow
Paclitaxel failed to increase the frequency of mEPSCs by dorsal root stimulation in α2δ1 knockout mice (Chen et al, 2019). These results indicated that a transition from being α2δ1-free to α2δ1-bound N-methyl-D-aspartate receptor (NMDAR) is essential for the activation of presynaptic NMDARs in the spinal dorsal horn (SDH) and the increase in glutamate release from the central terminals of presynaptic neurons

Summary

Frontiers in Cellular Neuroscience

Received: 24 April 2021 Accepted: 10 September 2021 Published: 30 September 2021. Citation: Cui W, Wu H, Yu X, Song T, Xu X and Xu F (2021) The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain. Neuropathic pain is mainly triggered after nerve injury and associated with plasticity of the nociceptive pathway in primary sensory neurons. In order to identify specific therapeutic targets, it is necessary to clarify the underlying mechanisms of neuropathic pain. It is well established that primary sensory neuron sensitization (peripheral sensitization) is one of the main components of neuropathic pain. As the target of gabapentin, the calcium channel subunit α2δ1 (Cavα2δ1) is a potential entry point in neuropathic pain research. Numerous studies have demonstrated that the upstream and downstream targets of Cavα2δ1 of the peripheral primary neurons, including thrombospondins, N-methyl-D-aspartate receptors, transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid family 1 (TRPV1), and protein kinase C (PKC), are involved in neuropathic pain. We reviewed and discussed the role of Cavα2δ1 and the associated signaling axis in neuropathic pain conditions

INTRODUCTION

CONCLUSION AND IMPLICATION

Findings

AUTHOR CONTRIBUTIONS