Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain

Abstract

Cav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supra-spinal level is almost unknown. In the Anterior Pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a sub-population of GABAergic neurons co-expressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high frequency bursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology.

Ion channels in cancer-induced bone pain: from molecular mechanisms to clinical applications

“…Increased voltage-gated sodium channel 1.7 (NaV1.7) expression leads to increased neuronal excitability and ultimately causes neuropathic pain in animal models (Li et al, 2018). In the early stage of nerve injury, the expression of the Cav3.2 channel and functional enhancement of damaged neurons lead to an increase in ectopic discharge frequency (Fayad et al, 2022). Transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential melastatin 8 (TRPM8) knockout mice demonstrated relief of pain sensitization in neuropathic models (Trevisan et al, 2016;de Caro et al, 2018).…”