Paired associative stimulation with a high-intensity cortical component and a high-frequency peripheral component in treatment of neuropathic pain after incomplete spinal cord injury – a pilot trial

STUDY DESIGN: Prospective interventional sham-controlled pilot study. OBJECTIVES: To investigate the effect of motor-tract paired-associative stimulation consisting of high-intensity transcranial magnetic stimulation and high-frequency electric stimulation of peripheral nerves (high-PAS) on moderate-to-severe upper limb neuropathic pain in patients with incomplete spinal cord injury compared with sham treatment in the same patients. SETTING: BioMag Laboratory, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. METHODS: High-PAS was applied for 4 weeks to 5 patients with incomplete, non-traumatic SCI and chronic neuropathic pain in upper limb(s). Median, ulnar, and radial nerves of the more painful hand were stimulated. The same patients also received sham stimulation for 4 weeks. Pain was measured with Verbal Rating Scale weekly and with Brief Pain Inventory before and after both stimulation periods and after follow-up of 8 weeks. RESULTS: Clinically significant relief in pain was not achieved with high-PAS or sham treatment. CONCLUSIONS: In this pilot study, clinically significant pain relief was not observed with high-PAS compared with sham treatment. Larger studies are needed to confirm these findings. Nevertheless, pain is not a contraindication for high-PAS in rehabilitation. The previously reported positive effect on milder neuropathic pain may be due to improved muscle activity, different pain types, or placebo effect. High-PAS targeting sensory tracts instead of motor tracts merits further investigation for pain treatment. TRIAL REGISTRATION: clinicaltrials.gov, ID NCT05362422.