Development and progression of mechanical allodynia in UC Davis-type 2 diabetes mellitus rats

Type 2 Diabetes (T2D) is a metabolic disease associated with sensory nerve damage. One of the most common complications of diabetes is neuropathy. A painful symptom of neuropathy that can develop is mechanical allodynia, which is a painful sensation to a normally non-painful stimulus. However, it is not known when symptoms of allodynia begin to show and how pain thresholds would change over time with T2D. Therefore, the purpose of this study was to determine the changes in pain threshold and to identify the onset of allodynia in a T2D rat model. Pain threshold was measured on male UC Davis type 2 diabetic (UCD-T2DM) rats (n=7) using von Frey monofilaments, which were applied to the L5 dermatome on the plantar surface of the hind paw. The lowest force that elicited a quick paw withdrawal was averaged between both hind paws. Mechanical allodynia was defined as a significant reduction in force that elicited a paw withdrawal. Pain threshold, non-fasted blood glucose, HbA1C and body weight were taken monthly from four to eight months of age. We found that non-fasted blood glucose from five to eight months of age (5mo: 388 ± 163 mg/dl, 6mo: 475 ± 145 mg/dl, 7mo: 504 ± 118 mg/dl, and 8mo: 577 ± 47 mg/dl) was significantly higher than the non-diabetic rats of four months (4mo: 239 ± 76 mg/dl). HbA1C values from six to eight months (6mo: 9.96 +/- 3.13%, 7mo: 11.5 ± 2.8%, and 8mo: 12.5 ± 0.73%) were significantly higher than that at four months (4mo: 5.8 ± 0.36%). Body weight was significantly higher at five to seven months (5mo: 609 ± 8.5g, 6mo: 603 ± 59g, and 7mo: 577 ± 76g) than at four (527.7 ± 12.3 g) and eight months (530 ± 56.6g). Pain threshold was significantly lower at six, seven and eight months (6mo: 15.7 ± 10.6g, 7mo: 10.36 ± 5.85g and 8mo: 8.95 ± 2.79g) compared to four months (32.78 ± 27.13g). Our data show that as blood glucose and HbA1C continued to increase, pain threshold continued to decrease. These findings suggest that mechanical allodynia increases as T2D progresses