Spinal cord stimulation in experimental chronic painful diabetic polyneuropathy: Delayed effect of High‐frequency stimulation

Abstract

BackgroundSpinal cord stimulation (SCS) has been shown to provide pain relief in painful diabetic polyneuropathy (PDPN). As the vasculature system plays a great role in the pathophysiology of PDPN, a potential beneficial side‐effect of SCS is peripheral vasodilation, with high frequency (HF) SCS in particular. We hypothesize that HF‐SCS (500 Hz), compared with conventional (CON) or low frequency (LF)‐SCS will result in increased alleviation of mechanical hypersensitivity in chronic experimental PDPN.MethodsDiabetes was induced in 8‐week‐old female Sprague–Dawley rats with an intraperitoneal injection of 65 mg/kg of streptozotocin (n = 44). Rats with a significant decrease in mechanical withdrawal response to von Frey filaments over a period of 20 weeks were implanted with SCS electrodes (n = 18). Rats were assigned to a cross‐over design with a random order of LF‐, CON‐, HF‐ and sham SCS and mechanical withdrawal thresholds were assessed with von Frey testing.ResultsCompared with sham treatment, the average 50% WT score for 5 Hz was 4.88 g higher during stimulation (p = 0.156), and 1.77 g higher post‐stimulation (p = 0.008). CON‐SCS resulted in 50% WT scores 5.7 g, and 2.51 g higher during (p = 0.064) and after stimulation (p < 0.004), respectively. HF‐SCS started out with an average difference in 50% WT score compared with sham of 1.87 g during stimulation (p = 0.279), and subsequently the steepest rise to a difference of 5.47 g post‐stimulation (p < 0.001).ConclusionsWe demonstrated a delayed effect of HF‐SCS on mechanical hypersensitivity in chronic PDPN animals compared with LF‐, or CON‐SCS.SignificanceThis study evaluates the effect of SCS frequency (5–500 Hz) on mechanical hypersensitivity in the chronic phase of experimental PDPN. High frequency (500 Hz) – SCS resulted in a delayed effect‐ on pain‐related behavioural outcome in chronic PDPN.

Nonlinear Relation Between Burst Dorsal Root Ganglion Stimulation Amplitude and Behavioral Outcome in an Experimental Model of Painful Diabetic Peripheral Neuropathy

“…Animals without mechanical hypersensitivity were excluded from the study. The presence of mechanical hypersensitivity was defined as a decrease of ≥0.2 unit in log 10 (10,000 x 50% WT) when compared to pre-STZ values (27)(28)(29).…”

Dorsal Root Ganglion Stimulation in Experimental Painful Diabetic Peripheral Neuropathy: Burst vs. Conventional Stimulation Paradigm

“…Animals without mechanical hypersensitivity were excluded from the study. The presence of mechanical hypersensitivity was defined as a decrease of ≥0.2 unit in log 10 (10,000 x 50% WT) when compared to pre-STZ values (15)(16)(17).…”

“…In the first week after STZ injection (week 1), blood glucose of the animals was measured to confirm DM (DM defined as blood glucose level ≥15 mmol/L (19)). Four weeks after STZ injection (week 4), animals were again tested for mechanical hypersensitivity, to select animals that developed PDPN (≥0.2 decrease in log 10 (10,000 x 50% WT) on Von Frey when compared to the pre-STZ baseline (15)(16)(17)) for DRGS implantation (week 5). PDPN animals received either Con-DRGS and Burst-DRGS in a randomized crossover design on days 2 and 3 postimplantation, or were assigned to a Sham-DRGS group (50% WT measured on day 2).…”

“…Thirteen animals required insulin treatment (blood glucose level ≥31.4 mmol/L). Twenty-five out of the 43 diabetic animals developed subsequent PDPN 4 weeks post-STZ injection (58%; ≥0.2 decrease in log 10 (10,000 x 50% WT) on Von Frey when compared to the pre-STZ baseline (15)(16)(17)), of which 22 were successfully implanted with a DRGS device. Two out of the 22 implanted PDPN animals were withdrawn from the study due to connector breakage before the first stimulation day, one animal was withdrawn from the study due to not being able to finish the complete study period (no motor threshold observed on second stimulation day), and two animals were excluded from the study because of high MT (MT ≥1 mA).…”

“…Over the years, preclinical research has provided valuable information with regard to the therapeutic effects of neuromodulation for PDPN. The effectiveness of SCS in experimental PDPN has been demonstrated in both the short (15,16) and long term (17). Interestingly, the first in vivo study to test the effectiveness of DRGS in an animal model of peripheral nerve injury was recently published (18).…”