• Nadine Gravius, Shafqat R Chaudhry, Sajjad Muhammad, Azize Boström, Sascha Gravius, Thomas Randau, Dirk Scheele, Philipp Westhofen, Johannes Kruppenbacher, Birgit Stoffel-Wagner, Christian Maier, Anna Weidlich, Thomas L Yearwood, Krishnan V Chakravarthy, Jeffery M Kramer, Rene Hurlemann, and Thomas M Kinfe.
• Department of Orthopedics and Trauma Surgery, University Hospital Bonn, Bonn, Germany.
• Neuromodulation. 2019 Jan 1; 22 (1): 44-52.

ObjectivesComplex regional pain syndrome (CRPS) and associated comorbidities have been linked to a pro-inflammatory state driven by different mediators. Targeted dorsal root ganglion stimulation (DRGSTIM ) suppressed pain levels and improved functional capacity in intractable CRPS. However, clinical trials assessing the impact of DRG stimulation on the neuroimmune axis are lacking.MethodsThis study enrolled 24 subjects (12 refractory CRPS patients plus suitably matched healthy controls) and performed immunoassays of inflammatory mediators in saliva and serum along with score-based assessments of pain, mood, and sleep quality at baseline and after three months of selective L4-DRGSTIM .ResultsAfter three-month L4-DRGSTIM CRPS associated pain significantly decreased. In addition, disturbed sleep and mood improved post-DRGSTIM , although statistically not significant. Significantly increased serum values of pro-inflammatory markers were detected pre- and post L4-DRGSTIM for high-mobility group box 1, tumor-necrosis factor α, interleukin (IL) 6, and leptin. IL-1β was significantly elevated pre-L4 DRGSTIM , but not posttreatment. Elevated anti-inflammatory IL-10 significantly decreased after three months in serum, while saliva oxytocin concentrations increased in CRPS subjects after L4-DRGSTIM (p = 0.65). No severe implantation and stimulation associated adverse events were recorded.ConclusionsSelective L4-DRGSTIM improved neuropathic pain and functional impairment in CRPS as previously reported. CRPS patients displayed a pro-inflammatory molecular pattern in serum. Serum anti-inflammatory IL-10 significantly declined, while saliva oxytocin nonsignificantly increased after L4-DRGSTIM . An evidence-based relational interpretation of our study is limited due to the uncontrolled study design. However, molecular profiling of biofluids (saliva, serum) represents a novel and experimental field in applied neuromodulation, which warrant further investigations to unveil mechanisms of neuroimmune modulation.© 2018 International Neuromodulation Society.

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