Non-invasive neuromodulation for chronic pain : A review of eight current methods and the evidence

Schmerz. 2026 Jun 12. doi: 10.1007/s00482-026-00952-7. Online ahead of print.

ABSTRACT

OBJECTIVE: This review summarizes the clinical evidence of non-invasive neuromodulation (NINM) in selected chronic pain conditions and examines whether combining neuromodulation with behavioral or psychological pain therapy improves therapeutic outcomes.

METHODS: Clinical studies and meta-analyses investigating NINM in neuropathic pain, migraine, fibromyalgia, and chronic low back pain were reviewed. Particular attention was given to studies integrating neuromodulation with active physiotherapy or psychological pain therapy.

RESULTS: The strongest evidence exists for repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), which demonstrate moderate effects in neuropathic pain, migraine, and fibromyalgia. Other approaches such as cranial electrical stimulation (CES), neurofeedback, and systolic extinction training (SET) show promising but more limited evidence. Transcutaneous electrical nerve stimulation (TENS) is only effective for acute back pain. Across conditions, neuromodulation alone often produces short-term improvements in pain, whereas multimodal interventions combining neuromodulation with behavioral therapy such as neurofeedback and SET appear to produce clinically significant pain reduction and remission.

DISCUSSION: A potential explanation for these findings lies in the interaction between neuromodulation and learning processes. Neuromodulatory interventions may transiently increase neural plasticity within the pain network. The reactivation of the brain stem (dorsal-medial nucleus tractus solitarius; dmNTS) might create a window during which adaptive learning processes can be facilitated. Behavioral interventions such as operant pain therapy and cognitive behavioral therapy can reinforce healthy behaviors and adaptive coping through mechanisms of classical and operant conditioning.

CONCLUSION: NINM should be considered not only as an isolated intervention but also as a neurophysiological facilitator of learning-based pain therapy. Future research should focus on personalized neuromodulation protocols, multimodal treatment approaches, and the identification of neurophysiological biomarkers that predict treatment response.

PMID:42283853 | DOI:10.1007/s00482-026-00952-7