Peripheral Nerve Denervation in Streptozotocin-Induced Diabetic Rats Is Reduced by Cilostazol

Area of Science:

• Neuroscience
• Pharmacology
• Endocrinology

Background:

• Diabetic neuropathy involves hyperglycemia-induced peripheral nerve damage.
• Previous studies showed cilostazol reduces painful neuropathy in diabetic rats.
• This study investigates cilostazol's effects on peripheral nerve fiber integrity in type I diabetic rats.

Purpose of the Study:

• To examine neuropathology in type I diabetic rats.
• To evaluate cilostazol's impact on peripheral small nerve fiber integrity.
• To assess cilostazol's efficacy in mitigating diabetic neuropathic pain.

Main Methods:

• Ninety Sprague-Dawley rats were divided into control, diabetic (DM), and DM groups treated with varying doses of oral cilostazol (10, 30, 100 mg/kg).
• Pain tolerance thresholds were assessed using thermal and mechanical stimuli.
• Immunohistochemistry and immunofluorescence analyzed nerve fiber markers (PGP9.5, P2X3, CGRP, TRPV-1) and glial cell activation in hind paw skin and spinal dorsal horn.

Main Results:

• Cilostazol ameliorated mechanical allodynia but not thermal analgesia in diabetic rats.
• Significant improvements in epidermal nerve fiber density (PGP9.5, P2X3, CGRP, TRPV-1) were observed with 30 and 100 mg/kg cilostazol, indicating reduced denervation.
• Cilostazol suppressed microglial activation and modulated astrocyte expression in the spinal dorsal horn.

Conclusions:

• Oral cilostazol effectively mitigated hyperglycemia-induced peripheral nerve damage and neuropathic pain in diabetic rats.
• The mechanism involves reducing peripheral nerve fiber damage and central sensitization.
• Cilostazol shows potential for managing diabetic neuropathy symptoms and preventing its early development.