Effects of combined entacapone and rTMS therapy on pain severity and serum inflammatory biomarkers (IL-6 and TNF-α) in Parkinson's disease

OBJECTIVE: To evaluate the efficacy of entacapone (EN) combined with high-frequency repetitive transcranial magnetic stimulation (rTMS) in treating pain in patients with Parkinson's disease (PD), with the primary outcome defined as the change in pain severity assessed by the Visual Analog Scale (VAS).Secondary outcomes included motor function (UPDRS), other pain dimensions (KPPS), depressive symptoms (HAMD), and levels of inflammatory markers (TNF-α and IL-6). METHODS: A total of 72 PD patients with pain were enrolled and randomly assigned to three groups: Group 1 (LD + sham stimulation), Group 2 (LD + EN + sham stimulation), and Group 3 (LD + EN + rTMS) and assessed via motor, pain, and depression scales (UPDRS/VAS/KPPS/HAMD) to evaluate the efficacy of the treatment, and also to observe the changes in the levels of interleukin (IL-6) and tumor necrosis factor (TNF-α), which are associated with pain in PD. RESULTS: After six months of combined pharmacotherapy and rTMS, the primary outcome, VAS score, demonstrated a significantly greater reduction in Group 3 compared to Group 2 (2.86 ± 1.25 vs. 8.22 ± 1.31, P < 0.05).In addition, from the indexes of inflammatory factors, this study found that after six months of regular and systematic treatment, the reduction in serum IL-6 and TNF-α levels was most pronounced in the combined therapy group (LD+EN+rTMS), with statistically significant differences compared to Group 2 (P = 0.003 for TNF-α). CONCLUSIONS: High-frequency rTMS, as a non-invasive neuromodulation technique combined with EN, improves muscle rigidity, alleviates depressive symptoms, reduces pain, and attenuates inflammatory factor secretion in PD patients, can improve muscle tension, regulate depression, relieve pain, and reduce the secretion of inflammatory factors in Parkinson's patients.This combined therapy was clinically effective and demonstrated a favorable safety profile, with no serious adverse events reported and only mild, transient side effects (e.g., scalp discomfort, headache) observed in the rTMS group. However, its long-term efficacy requires further investigation.