Michael T. Nelson

TL;DR: It is found that, in parallel with the development of diabetes-induced pain, T-type current density increased by twofold in medium-size cells from L4–L5 dorsal root ganglia (DRG) with a depolarizing shift in steady-state inactivation, and increased cellular excitability manifested as a lower threshold for burst firing in diabetic than in control cells.

TL;DR: The finding that T-type currents are upregulated in a CCI model of peripheral neuropathy and earlier pharmacological and molecular studies suggest that T -type channels may be potentially useful therapeutic targets for the treatment of neuropathic pain associated with partial mechanical injury to the sciatic nerve.

TL;DR: It is demonstrated that the endogenous reducing agent l-cysteine lowers the threshold for nociceptor excitability and induces burst firing by increasing the amplitude of T-type currents and shifting the gating parameters ofT-type channels.

TL;DR: Treatment of diabetic rats with daily insulin injections reversed T‐current alterations in DRG neurons in parallel with reversal of thermal and mechanical hypersensitivities in vivo, confirming that CaV3.2 T‐channels, important signal amplifiers in peripheral sensory neurons, may contribute to the cellular hyperexcitability that ultimately leads to the development of painful PDN.

TL;DR: It is demonstrated that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn2+ ions off specific extracellular histidine residues on Cav3.2 T-channels, thus relieving tonic channel inhibition, enhancing Cav3-2 currents, and lowering the threshold for nocICEptor excitability in vitro and in vivo.