Objective: Complex regional pain syndrome (CRPS) is characterized by continued pain disproportional to the inciting event, sensory abnormalities, vasomotor and sudomotor disturbances, and motor and trophic changes. Inflammatory involvement has been demonstrated in past CRPS studies resulting in pain, swelling, and warmth. Currently, it is unknown whether spinal cord stimulation (SCS) has immunomodulatory properties. The aim of this study was to determine whether SCS has immunomodulatory properties in CRPS patients. Methods: The primary outcome parameters are cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF-α, IFN-γ), chemokines (IP-10 and Eotaxin), and growth factors (VEGF, PDGFbb, and basic FGF) from interstitial fluid of artificial skin blisters before (T0—baseline without SCS) and after SCS therapy (T1—40 Hz standard frequency stimulation and T2—preferred frequency stimulation). Secondary outcome parameters were baseline demographics, CRPS signs, symptoms, and phenotype (inflammatory, vasomotor, dystonia, or neuropathic). Results were analyzed by means of a MANOVA repeated measures design. Results: After SCS, the expression of both pro- and anti-inflammatory cytokines decreased over time in both the CRPS affected extremity and the contralateral extremity. The levels of IP-10, Eotaxin, VEGF, and PDGFbb were also significantly reduced bilaterally. There were no significant changes in IL-6 and TNF-α before and after SCS. The sensory signs, symptoms, and phenotype improved after SCS. Discussion: SCS in CRPS patients attenuates T-cell activation, improves peripheral tissue oxygenation and decreases anti-angiogenetic activity which results in diminished endothelial dysfunction and improved bloodflow. The possible immunomodulatory effects of SCS opens new therapeutic possibilities in diseases with the involvement of the immune system and vasomotor disturbances, and requires further research on these mechanisms of action.

Additional Metadata
Keywords Burst SCS, chemokine, complex regional pain syndrome, CRPS phenotype, cytokine, growth factor, high-frequency SCS, immunomodulation, inflammation, spinal cord stimulation, T-cells, vasodilation
Persistent URL dx.doi.org/10.1111/ner.12704, hdl.handle.net/1765/104169
Journal Neuromodulation
Kriek, N, Schreurs, M.W.J, Groeneweg, J.G, Dik, W.A, Tjiang, G.C.H, Gültuna, I. (Ismail), … Huygen, F.J.P.M. (2018). Spinal Cord Stimulation in Patients With Complex Regional Pain Syndrome: A Possible Target for Immunomodulation?. Neuromodulation, 21(1), 77–86. doi:10.1111/ner.12704