N-glycosylation of Cav3.2 channel in DRG neurons of myelinated A-fiber contributes to diabetic mechanical allodynia

doi:10.3969/j.issn.1674-8115.2025.11.005

Abstract

Abstract:

Objective ·To investigate the association of Cav3.2 channel N-glycosylation in myelinated A-fiber dorsal root ganglion (DRG) neurons with diabetic mechanical allodynia (MA). Methods ·Diabetic rat models were induced by a single intraperitoneal injection of streptozotocin. Pain behavior assessments, including evaluations of MA and thermal hyperalgesia (TH), were conducted on a weekly basis. Diabetic rats exhibiting TH were subsequently categorized into two subcategories based on the onset of mechanical allodynia by the third week. The impact of N-glycosylation on both the expression of Cav3.2 channels in DRG neurons and pain behaviors was investigated through sequential administration of neuraminidase (NEU) and TTA-P2, a selective blocker of T-type calcium channels, after C-unmyelinated fiber blockage by the application of resiniferatoxin (RTX). The extent of Cav3.2 N-glycosylation was quantitatively compared between diabetic rats with and without MA by analyzing the N-terminal fragment of Cav3.2 following de-glycosylation. Results ·Higher levels of Cav3.2 expression in myelinated A-fiber DRG neurons were observed in diabetic rats with MA compared to those without MA (P<0.001). NEU-induced de-glycosylation led to a reduction in Cav3.2 expression across all groups, with diabetic rats with MA maintaining higher levels of the Cav3.2 expression than those without MA (P<0.05). It was observed that RTX eliminated only TH and not MA, whereas NEU had a restorative effect on both TH and MA, similar to TTA-P2. Diabetic rats with MA exhibited increased expression of N-terminal fragments compared to those without MA (P<0.001). Conclusion ·N-glycosylation of the Cav3.2 channel within DRG neurons of myelinated A-fiber is a contributing factor to diabetic MA.

Key words: diabetic peripheral neuropathy, Cav3.2 channel, mechanical allodynia, dorsal root ganglion, glycosylation

CLC Number:

R587.2

LIAO Chenlong, LI Shuo, XU Xin, ZHANG Yue, ZHANG Wenchuan. N-glycosylation of Cav3.2 channel in DRG neurons of myelinated A-fiber contributes to diabetic mechanical allodynia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(11): 1458-1465.

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References 33

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