Dorsal Root Ganglion Stimulation in Experimental Painful Diabetic Polyneuropathy: Delayed Wash-Out of Pain Relief After Low-Frequency (1Hz) Stimulation

Objective Up until now there is little data about the pain relieving effect of different frequency settings in DRGS. The aim of this study was to compare the pain relieving effect of DRGS at low-, mid-, and high-frequencies and Sham-DRGS in an animal model of painful diabetic neuropathy (PDPN). Material and Methods Diabetes mellitus was induced by an intraperitoneal injection of streptozotocin in 8-week-old female Sprague-Dawley rats (n = 24; glucose >= 15 mmol/L: n = 20; mechanical hypersensitivity: n = 15). Five weeks later, a DRGS device was implanted at the L5 DRG. Ten animals were included for stimulation, alternating 30 minutes of low (1 Hz)-, mid (20 Hz)-, and high (1000 Hz)-frequencies and Sham-DRGS during four days, with a pulse width of 0.2 msec (average amplitude: 0.19 +/- 0.01 mA), using a randomized cross-over design. The effect on mechanical hypersensitivity of the hind paw to von Frey filaments was evaluated. Results All DRGS frequencies resulted in a complete reversal of mechanical hypersensitivity and "a clinically relevant reduction" was achieved in 70-80% of animals. No significant differences in maximal pain relieving effect were found between the different frequency treatments (p = 0.24). Animals stimulated at 1000 and 20 Hz returned to baseline mechanical hypersensitivity values 15 and 30 min after stimulation cessation, respectively, while animals stimulated at 1 Hz did not. Conclusions These results show that DRGS is equally effective when applied at low-, mid-, and high-frequency in an animal model of PDPN. However, low-frequency-(1 Hz)-DRGS resulted in a delayed wash-out effect, which suggests that this is the most optimal frequency for pain therapy in PDPN as compared to mid- and high-frequency.