Abstract
AimsIt is hypothesized that dorsal root ganglion stimulation (DRGS), sharing some of the mechanisms of traditional spinal cord stimulation (SCS) of the dorsal columns, induces γ‐aminobutyric acid (GABA) release from interneurons in the spinal dorsal horn.MethodsWe used quantitative immunohistochemical analysis in order to investigate the effect of DRGS on intensity of intracellular GABA‐staining levels in the L4‐L6 spinal dorsal horn of painful diabetic polyneuropathy (PDPN) animals. To establish the maximal pain relieving effect, we tested for mechanical hypersensitivity to von Frey filaments and animals received 30 minutes of DRGS at day 3 after implantation of the electrode. One day later, 4 Sham‐DRGS animals and four responders‐to‐DRGS received again 30 minutes of DRGS and were perfused at the peak of DRGS‐induced pain relief.ResultsNo significant difference in GABA‐immunoreactivity was observed between DRGS and Sham‐DRGS in lamina 1‐3 of the spinal levels L4‐6 neither ipsilaterally nor contralaterally.ConclusionsDorsal root ganglion stimulation does not induce GABA release from the spinal dorsal horn cells, suggesting that the mechanisms underlying DRGS in pain relief are different from those of conventional SCS. The modulation of a GABA‐mediated “Gate Control” in the DRG itself, functioning as a prime Gate of nociception, is suggested and discussed.
Highlights
The results of this study indicate that dorsal root ganglion stimulation (DRGS) does not result in decreased levels of in‐ tracellular GABA‐IR in the spinal dorsal horn and does not in‐ duce GABA release
The dorsal root ganglion (DRG) appears to be an appealing site for neurostim‐ ulation,[45] and clinical evidence indicates that DRGS provides ef‐ ficacious pain relief in neuropathic pain sufferers,[46,47,48,49,50] which is confirmed by experimental studies.[35,36]
With DRGS the electrical fields have a direct effect on the neural tissues that are patho‐ physiologically involved in the chronic pain disease condition
Summary
The protocols for this study were approved by the Animal Care Committee of the Maastricht University Medical Centre (DEC 2013‐079). For com‐ parisons of grayscale values between levels (L4 vs L5 vs L6), treat‐ ments (DRGS vs Sham‐DRGS), and left‐right differences (ipsilateral vs contralateral), a two‐way analysis of variance (ANOVA) was used, followed by a Sidak's multiple comparisons test. In the Sham‐DRGS group, the log[10] (10 000 × 50% WT) dropped significantly from 5.041 pre‐STZ injection to 4.416 pre‐Sham‐ DRGS (P < 0.05).[36] The mean log[10] (10 000 × 50% WT) value of the animals that were selected for GABA‐IR analyses (n = 8) decreased from 4.99 ± 0.05 pre‐STZ injection to 4.50 ± 0.06 pre‐implanta‐ tion (4 weeks post‐STZ injection, P < 0.01). No differences in GABA‐IR were found between DRGS and Sham‐DRGS in lamina 1‐3 of spinal level L4‐6, neither ipsilaterally nor contralaterally (Figure 2).
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