• Eva Koetsier, Glenn Franken, Jacques Debets, Lonne Heijmans, van KuijkSander M JSMJDepartment of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center+, Maastricht, The Netherlands., Bengt Linderoth, Elbert A Joosten, and Paolo Maino.
• Pain Management Center, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Lugano, Switzerland.
• CNS Neurosci Ther. 2020 Jan 1; 26 (1): 136-143.

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.© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

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