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

Abstract

Background and objective: Dorsal root ganglion stimulation (DRGS) has recently emerged as a neuromodulation modality in the treatment of chronic neuropathic pain. The objective of this study was to compare the efficacy of different Burst-DRGS amplitudes in an experimental model of painful diabetic peripheral neuropathy (PDPN). Methods: Diabetes mellitus was induced in female Sprague–Dawley rats by intraperitoneal injection of streptozotocin (STZ, n = 28). Animals were tested for mechanical hypersensitivity (von Frey paw withdrawal test) before, and four weeks after STZ injection. PDPN rats (n = 13) were implanted with a unilateral bipolar electrode at the L5 DRG. Animals received Burst-DRGS at 0%, 10%, 33%, 50%, 66%, and 80% of motor threshold (MT) in a randomized crossover design on post-implantation days 2–7 (n = 9). Mechanical hypersensitivity was assessed before stimulation onset, 15 and 30 min during stimulation, and 15 and 30 min after stimulation. Results: Burst-DRGS at amplitudes of 33%, 50%, 66%, and 80% MT resulted in significant attenuation of STZ-induced mechanical hypersensitivity at 15 and 30 min during stimulation, as well as 15 min after cessation of stimulation. No effect on mechanical hypersensitivity was observed for Burst-DRGS at 0% MT and 10% MT. Optimal pain relief and highest responder rates were achieved with Burst-DRGS at 50–66% MT, with an estimated optimum at 52% MT. Conclusion: Our findings indicate a nonlinear relationship between Burst-DRGS amplitude and behavioral outcome, with an estimated optimal amplitude of 52% MT. Further optimization and analysis of DRGS driven by insights into the underlying mechanisms related to the various stimulation paradigms is warranted.