• Glenn Franken, Perla Douven, Jacques Debets, and JoostenElbert A JEAJDepartment of Anesthesiology and Pain Management, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, Maastricht Un.
• Department of Anesthesiology and Pain Management, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
• Neuromodulation. 2021 Jun 1; 24 (4): 639-645.

Background And ObjectiveThe sensory cell somata in the DRG contain all equipment necessary for extensive GABAergic signaling and are able to release GABA upon depolarization. With this study, we hypothesize that pain relief induced by conventional dorsal root ganglion stimulation (Con-DRGS) in animals with experimental painful diabetic peripheral neuropathy is related to the release of GABA from DRG neurons. With use of quantitative immunocytochemistry, we hypothesize DRGS to result in a decreased intensity of intracellular GABA-immunostaining in DRG somata.Materials And MethodsFemale Sprague-Dawley rats (n = 31) were injected with streptozotocin (STZ) in order to induce Diabetes Mellitus. Animals that developed neuropathic pain after four weeks (Von Frey) were implanted with a unilateral DRGS device at L4 (n = 14). Animals were then stimulated for 30 min with Con-DRGS (20 Hz, pulse width = 0.2 msec, amplitude = 67% of motor threshold, n = 8) or Sham-DRGS (n = 6), while pain behavior (von Frey) was measured. DRGs were then collected and immunostained for GABA, and a relation to size of sensory cell soma diameter (small: 12-26 μm, assumed to be C-fiber related sensory neurons; medium: 26-40 μm, assumed to be Aδ related sensory neurons; and large: 40-54 μm, assumed to be Aβ related sensory neurons) was made.ResultsDRGS treated animals showed significant reductions in STZ-induced mechanical hypersensitivity. No significant differences in GABA immunostaining intensity per sensory neuron cell soma type (small-, medium-, or large-sized) were noted in DRGs of stimulated (Con-DRGS) animals versus Sham animals. No differences in GABA immunostaining intensity per sensory cell soma type in ipsi- as compared to contralateral DRGs were observed.ConclusionCon-DRGS does not affect the average intracellular GABA immunofluorescence staining intensity in DRG sensory neurons of those animals which showed significant pain reduction. Similarly, no soma size related changes in intracellular GABA immunofluorescence were observed following Con-DRGS.© 2021 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC on behalf of International Neuromodulation Society.

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