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Updated: May 20, 2026

Rapid Determination of the Thermal Nociceptive Threshold in Diabetic Rats
Published on: May 17, 2012
Generalized depletion of free nerve endings and decrease of cutaneous nervous innervation in streptozotocin-induced
Chi-Chun Chu1, Shwun-De Wang, Joseph S Chiang
1Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Background:
The loss of peripheral nerve fiber is evident in chronic painful diabetic neuropathy. However, the correlation between peripheral fiber loss and the genesis of pain is unclear. Using the streptozotocin-induced diabetic rat model and focusing on free nerve endings, we attempted to investigate the peripheral changes that elicit pain syndromes in diabetes.
Methods:
Diabetes was induced in rats using 75 mg/kg streptozotocin, while controls received saline solution. "Painful" rats with thermal or mechanical hypersensitivity and "painless" rats (without significant threshold changes) were enrolled. The peripheral nerve endings were immunostained using protein gene product 9.5 in footpad skin sections. The peripheral nerve densities in each behavior group were calculated and averaged.
Results:
A progressive loss of protein gene product 9.5-blotted nerve fibers was noted after diabetes was induced and as the duration of hyperglycemia proceeded. Painful and painless diabetic rats have similar histological nerve fiber loss including depleted epidermal free nerve endings.
Conclusion:
The results indicated that there are undiscovered pathological changes that are sensitizing the injured nerve fiber in periphery.
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