Material and methods
depression, Depression, Pain, pain
Adult patients using DRG-S and followed up at the Department of Functional Neurosurgery and Stereotaxy of the Heinrich-Heine-University Düsseldorf were invited to participate in the study. Significant pain possibly confounding the study results was an exclusion criterion. Informed consent was obtained. The study was originally approved by the Ethics Committee of the Medical Faculty under the number 2020–1120; the new study design including low-frequency stimulation was approved with an amendment. Registration in the German Clinical Trials Register (DRKS) is under DRKS00022557.Neuropathic pain was assessed with PainDetect (0–38 points) at the baseline, when all patients were being stimulated with 20 Hz. All subjects tested in a randomized order four different settings of stimulation parameters: stimulation frequencies of 4 Hz, 20 Hz, 60 Hz, and sham stimulation. Stimulation amplitude was individually optimized in each case, so that stimulation was at subthreshold level for the entire duration of the study. Subjects and investigators were blinded; a study nurse had access to unblinded data. Each stimulation setting was tested for 5 days and followed by a 2-day washout period. There was also a washout period before the study starts. When patients reported intolerable pain without stimulation, the washout period was shortened to a single day. In case of intolerable pain during a test period, the testing was shortened. A study nurse programmed stimulation parameters in advance, so that patients could randomly change them each week at home. At the end of each phase, patients were interviewed by phone and completed numbered questionnaires.During the study, evaluation of pain intensity and quality was done using the visual analog scale and McGill Pain Questionnaire (MPQ, 0–78 points); the prevalence of depression was assessed with the Beck Depression Inventory (BDI, 0–63 points) and the quality of life with EQ-5D-5L (index 0–1).Repeated measurement one-way ANOVA was used for comparison between baseline data and measurements at the different frequency settings; Tukey’s test was selected for post hoc analysis.