N-Glycosylation of Cav3.2 Channel in Myelinated A-Fibre Dorsal Root Ganglion Neurons Contributes to Mechanical Allodynia in Diabetic Rats.

Abstract

Objective: To investigate the role of Cav3.2 channel N-glycosylation in myelinated A-fibre dorsal root ganglion (DRG) neurons in the development of diabetic mechanical allodynia (MA).

Methods: Type 1 diabetes was induced in rats via a single intraperitoneal injection of streptozotocin. Pain behaviour, including MA and thermal hyperalgesia (TH), was assessed weekly. Diabetic rats with TH were further divided into 2 subgroups according to the presence of MA by the third week. The impact of N-glycosylation on Cav3.2 expression and pain behaviours was investigated through sequential intraplantar administration of neuraminidase (NEU) and TTA-P2, a selective blocker of T-type calcium channels. The Cav3.2 N-glycosylation levels were compared between diabetic rats with and without MA by analyzing the N-terminal fragment after enzymatic deglycosylation.

Results: Cav3.2 expression in myelinated A-fibre DRG neurons was significantly higher in diabetic rats with MA than in those without (p<0.001). NEU-induced deglycosylation reduced Cav3.2 expression in all groups, although diabetic rats with MA still had higher expression than those without (p<0.05). Resiniferatoxin eliminated TH but not MA, whereas NEU alleviated both, similar to TTA-P2. Diabetic rats with MA exhibited increased expression of Cav3.2 N-terminal fragments compared with those without (p<0.001).

Conclusion: N-glycosylation of the Cav3.2 channel in DRG neurons of myelinated A-fibres contributes to diabetic MA.