The Development and Progression of Mechanical Allodynia in UC, Davis Type 2 Diabetic Rats

Abstract

Type 2 diabetes (T2DM) is a metabolic disorder that can lead to many neuropathic complications such as mechanical allodynia, which is perceived pain caused by a normally non‐painful stimulus. T2DM is also associated with exaggerated pressor and cardioaccelerator responses to skeletal muscle contraction, namely the exercise pressor reflex. The mechanisms by which diabetes elicits these effects are not fully understood; however, both mechanical allodynia and the exercise pressor reflex are evoked by thin‐fiber afferent activity. The purpose of this study was to utilize noninvasive techniques to monitor the development and progression of diabetes‐induced neuropathy in thin‐fiber afferents. We used male UC Davis T2DM (n=9) rats from the age of 4 to 7 months to model the progression of T2DM. We took monthly measurements of blood glucose, HbA1c, and body weight. We also measured changes in mechanical sensitivity using von Frey filaments. Filaments were applied to the L5 dermatome on the plantar side of the left and right hind paws, between the footpads; the lowest force eliciting an abrupt paw withdrawal was measured and averaged between paws. We found that blood glucose (4mo: 255±28 mg/dl, 5mo: 366±50 mg/dl, 6mo: 417±58 mg/dl, 7mo: 453±49 mg/dl) and HbA1c (4mo: 5.7±0.2%, 5mo: 6.6±0.4%, 6mo: 9.3±1.2%, 7mo: 10.3±1.2%) were above the diabetic threshold (300 mg/dl, 6.5%) at 5, 6, and 7 months of age; they were significantly higher at 6 and 7 months, compared to 4 months, p<0.05. Body weight was significantly higher at 5, 6, and 7 months compared to 4 months (4mo: 525±4g, 5mo: 609±3g, 6mo: 620±21g, 7mo: 610±31g; p<0.05). Sensitivity to von Frey filaments was significantly greater, indicating mechanical allodynia, at 6 and 7 months compared to 4 months (4mo: 29±3.2 g, 5mo: 26.3±4.5 g, 6mo: 14.1±3.3 g, 7mo: 9.7±1.7 g; p<0.05). We conclude that mechanical allodynia progresses in severity as the rats develop and progress with T2DM. Moreover, these observations may provide insight to diabetes‐induced changes in thin‐fiber dependent reflexes, such as the exercise pressor reflex.Support or Funding InformationN/AThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.