OBJECTIVE: To determine if a physics-based combination of simultaneous static and time-varying dynamic magnetic field stimulation to the wrist 4 hours/day for 2 months can reduce subjective neuropathic pain and influence objective electrophysiologic parameters of patients with carpal tunnel syndrome (CTS). METHODS: Randomized, double-blinded, placebo-controlled trial of 36 symptomatic hands. Primary endpoints were visual analog scale (VAS) and neuropathic pain scale (NPS) scores at baseline and 2 months and a Patient's Global Impression of Change (PGIC) questionnaire at the end of 2 months. Secondary endpoints were neurologic examination, median nerve distal latencies (compound muscle action potential [CMAP]/sensory nerve action potential [SNAP]), dynamometry, pinch gauge readings, and current perception threshold (CPT) scores. An "active" device was provided gratis at the end of the study, with 15 subjects voluntarily remaining within the open protocol an additional 2-10 months and using the preselected primary and secondary parameters. RESULTS: (two months). Of the 31 hands, 25 (13 magnet, 12 sham) had moderate to severe pain (VAS > 4). The VAS and PGIC revealed a nonsignificant pain reduction. NPS analyses (anova) demonstrated a statistically significant reduction of "deep" pain (35% downward arrow vs 12% upward arrow, P = 0.018), NPS Total Composite (decreases of 42% vs 24%, P = 0.042), NPS Total Descriptor Score (NPS 8; 43% vs 24%), and NPS 4 (42% vs 11%). Motor strength, CMAP/SNAP, and CPT scores were not significantly changed. Of the 15 hands with up to 10 months of active PEMF (pulsed electromagnetic fields) exposure, there was objective improvement in nerve conduction (CMAP = 53%, SNAP = 40%, >1 SD), and subjective improvement on examination (40%), pain scores (50%), and PGIC (70%). No detectable changes in motor strength and CPT. CONCLUSIONS: PEMF exposure in refractory CTS provides statistically significant short- and longterm pain reduction and mild improvement in objective neuronal functions. Neuromodulation appears to influence nociceptive-C and large A-fiber functions, probably through ion/ligand binding.