Effectiveness of dorsal root ganglion stimulation and dorsal column spinal cord stimulation in a model of experimental painful diabetic polyneuropathy

Abstract

Summary Aims Conventional dorsal root ganglion stimulation (DRGS) is known to achieve better pain‐paresthesia overlap of difficult‐to‐reach areas like the feet compared to dorsal column spinal cord stimulation (SCS). As in painful diabetic polyneuropathy (PDPN) pain is mostly present in the feet, we hypothesized that DRGS is more effective in relieving pain in PDPN when compared to SCS. Methods Diabetes was induced in female Sprague‐Dawley rats with an intraperitoneal injection of 65 mg/kg of streptozotocin (STZ; n = 48). Rats with a significant decrease in mechanical paw withdrawal response to von Frey filaments 4 weeks after injection were implanted with DRGS electrodes (n = 18). Rats were assigned to DRGS (n = 11) or sham‐DRGS (n = 7). Mechanical paw withdrawal thresholds (WT, measured in grams) in response to DRGS (50 Hz, 0.18 ± 0.05 mA) were assessed with von Frey testing. The results of the experiments on these animals were compared to the results of a previous study using exactly the same model on PDPN animals selected for SCS (n = 8) (40‐50 Hz, 0.19 ± 0.01 mA) and sham‐SCS (n = 3). Results In the SCS group, the log10 (10 000 × 50% WT) increased from 4910 to 5211 at t = 15 minutes (P < 0.05) and 5264 at t = 30 minutes (P = 0.11). In the DRGS group, the log10 (10,000 × 50% WT) increased from 4376 to 4809 at t = 15 minutes (P < 0.01) and 5042 at t = 30 minutes (P < 0.01). Both DRGS and SCS induced a similar and complete reversal of mechanical hypersensitivity. After cessation of stimulation (t = 60), the return of the log10 (10 000 × 50% WT) response was significantly faster with DRGS than that of SCS (P < 0.05). Conclusions We conclude that conventional DRGS is as effective as SCS in reduction of PDPN‐associated mechanical hypersensitivity in STZ‐induced diabetic rats. The wash‐in effect of DRGS and SCS was similar, but DRGS showed a faster washout course. Long‐term efficacy should be studied in future animal research.

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

“…In the present study, the DRGS mid-frequency was set at 20 Hz, which is the frequency most frequently used for DRGS in humans (7,8,17,21,22). In previous DRGS-animal studies, frequencies of 20-50 Hz were used, which resulted in a significant reversal of neuropathic pain behavior (11,17). Until now there is little data about the use of HF for DRGS.…”

“…Optimization of the stimulation frequency might result in additional beneficial effects in experimental PDPN. The results of a recently published experimental study showed that conventional DRGS (50 Hz) is equally effective as conventional SCS (40–50 Hz) in reduction of PDPN‐associated mechanical hypersensitivity in experimental PDPN. Both SCS and DRGS induced a complete reversal of mechanical hypersensitivity, which was obtained after 15 min in the SCS group vs. after 30 min in the DRGS group.…”

Mechanism of dorsal root ganglion stimulation for pain relief in painful diabetic polyneuropathy is not dependent on GABA release in the dorsal horn of the spinal cord

“…Under general anesthesia, bipolar electrode was implanted unilaterally at the L5 DRG, according to the earlier described procedure adapted from Pan et al In short, via a paravertebral incision the intervertebral foramen was exposed, the foramen was opened, and the anode and cathode were implanted at the DRG. The electrode was then secured into the transverse process followed by closure of the incision in layers.…”

“…For comparison with previous experimental studies regarding neurostimulation in PDPN animals, we used time and design as in previous (published) experiments . Animals were stimulated for 30 minutes at days 3 and 4 following implantation.…”

“…Animals were stimulated for 30 minutes at days 3 and 4 following implantation. The stimulation on day 3 was meant to establish the maximal pain relieving effect of DRGS, while the stimulation on day 4 was performed to activate the mechanisms of action before perfusing the animals at the “peak of DRGS‐induced pain relief.” For stimulation, the implanted electrode was connected to the pulse generator (A‐M systems MultiStim Model 3800, fitted with an A‐M systems 3820 stimulus isolator [A‐M systems, Sequim, WA, USA]). To assess motor thresholds (MT), the current amplitude was increased during stimulation at 2 Hz with a pulse width of 0.2 ms, defining MT as the current at which any further increase resulted in hind limb movement.…”