Analgesic efficacy of non-invasive neuromodulation techniques in chronic cancer pain: a systematic review

Purpose Chronic pain remains one of the most frequent and disabling symptoms of cancer, arising from tumors and/or treatments, and is poorly controlled in 40% of patients. Non-invasive brain stimulation (NIBS) is now widely recommended in drug-refractory neuropathic pain, but its effectiveness in chronic cancer-related pain remains unknown. A few observational studies and randomized controlled trials (RCTs) have assessed the effectiveness of NIBS on pain in this population. Methods A systematic review of neuromodulation studies on patients with chronic cancer-related pain involving transcranial direct currents stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) was conducted to estimate the analgesic efficacy, safety and feasibility in clinical routine. Results Eleven publications (N = 298 patients) were included and analyzed. For tDCS, three RCT had a moderate effect size of 0.7 [0.6; 0.9] on a rating scale (0-10), and two case reports showed a significant decrease of pain intensity on average by -4.25 +/- 0.36 points. The rTMS provided similar pain relief, with two RCTs showing a large effect size of 0.9 [0.7; 1.1], two observational study studies reporting a significant pooled effect on pain intensity (-0.9 [-1.6; -0.1] and -2.3 [-3.3; -1.3]), and two case reports where pain was reduced on average by -4.75 +/- 0.36 points. None of these studies reported serious adverse events, and discontinuations of treatment were associated with cancer complications. Conclusions NIBS appears to have an analgesic effect in cancer-related pain. However, due to the high heterogeneity of pain conditions, placebo-controlled trials with larger and homogeneous patient cohorts are required to confirm these promising results.