Accumulation of Cav3.2 T-type Calcium Channels in the Uninjured Sural Nerve Contributes to Neuropathic Pain in Rats with Spared Nerve Injury

Abstract

Injuries to peripheral nerve fibers induce neuropathic pain. But the involvement of adjacent uninjured fibers to pain is not fully understood. The present study aims to investigate the possible contribution of Cav3.2 T-type calcium channels in uninjured afferent nerve fibers to neuropathic pain in rats with spared nerve injury (SNI). Aβ-, Aδ- and C-fibers of the uninjured sural nerve were sensitized revealed by in vivo single-unit recording, which were accompanied by accumulation of Cav3.2 T-type calcium channel proteins shown by Western blotting. Application of mibefradil, a T-type calcium channel blocker, to sural nerve receptive fields increased mechanical thresholds of Aβ-, Aδ- and C-fibers, confirming the functional involvement of accumulated channels in the sural nerve in SNI rats. Finally, perineural application of mibefradil or TTA-P2 to the uninjured sural nerve alleviated mechanical allodynia in SNI rats. These results suggest that axonal accumulation of Cav3.2 T-type calcium channels plays an important role in the uninjured sural nerve sensitization and contributes to neuropathic pain.

Cdk5-Dependent Phosphorylation of CaV3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers

“…In particular, a drastic decrease in Ca V 3.2 expression was observed in the spinal nerves of animals subjected to SNL compared with shamoperated controls, and a significant increase (ϳ2.5-fold) in the Ca V 3.2 expression in the DRG after SNL was also observed. Together, these data suggest that there is an accumulation of Ca V 3.2 channels in the DRG, as a result of a decrease in the channels in the spinal nerves (Chen et al, 2018;Liu et al, 2019).…”

Enhanced T-type calcium channel 3.2 activity in sensory neurons contributes to neuropathic-like pain of monosodium iodoacetate-induced knee osteoarthritis

“…Ca V 3.2 channels that modulate the function of peripheral and central nociceptive pathways by influencing peripheral sensory perception, neuronal excitability, and SC synaptic plasticity and neurotransmitter release. 18 Elevated expression and/or enhanced functionality of Ca V 3.2 channels have been well-defined, 20 in overall, a range of painful conditions across a variety of animal models, including inflammatory pain, 57 , 58 neuropathic pain, 59 , 60 diabetic peripheral neuropathic pain, 61 – 63 chemotherapy-induced peripheral neuropathy, 64 and postsurgical pain model (i.e. paw incision).…”

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

“…In injured DRG, increased levels of IL-10 were thought to lead to decreased Cav2.2 in injured neurons. Cav3.2 expression also changes after injury, possibly increasing within uninjured peripheral nerve fibers and contributing to increased excitability and lower mechanical threshold in a subset of C and Aδ fibers (Chen et al, 2018).…”