Painful diabetic neuropathy (PDN) is a serious complication of diabetes and occurs in approximately 20% of diabetic patients. In a recent RCT, 10kHz spinal cord stimulation (10kHz SCS) was shown to be a promising therapy for PDN, in both pain reduction and possible neurological improvements (Petersen et al 2021). In this study, we aimed to observe the behavioral effects of 10kHz SCS on PDN using streptozotocin (STZ)-induced diabetic rats. We established four testing groups: Naïve controls, STZ controls, STZ+Sham SCS, and STZ+10kHz SCS. A single effective dose (60 mg/kg) of the cytotoxic agent STZ caused the rats to become hyperglycemic within 72 hours and lasted for several weeks. These STZ-injected rats also showed a significant and continuous reduction in body weight in comparison to Naïve control rats. Using the von Frey test for mechanical allodynia, we observed that 14 days of 24h/day low-intensity (30% of motor threshold) 10kHz SCS significantly elevated the mechanical pain withdrawal thresholds compared to STZ controls or STZ+Sham SCS animals, reaching statistical equivalence to Naïve controls. In a thermal preference assay, all animals exhibited a training effect towards less activity and more preference to the room temperature side vs the non-painful heat side of a two-temperature chamber over the several-week protocol. We found that STZ-injected animals demonstrated significantly less exploration activity in the 10min testing periods compared to Naïve controls but neither the thermal preference nor the total distance they traveled were restored after 14 days of 10kHz SCS. Our results demonstrate that 10 kHz SCS resulted in behavioral outcomes reflective of the mechanical pain reduction in the PDN rodent model. These findings provide supporting evidence for the recent RCT data and underscore the conclusion that 10kHz SCS can effectively treat patients with refractory PDN. Disclosure D.Wang: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. K.Lee: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.
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