# 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

**Authors:** Kirsi Holopainen, Markus Pohjonen, Erika Kirveskari, Selja Vaalto, Jyrki P. Mäkelä, Jari Arokoski, Anastasia Shulga

PMC · DOI: 10.1038/s41394-026-00729-1 · Spinal Cord Series and Cases · 2026-03-04

## TL;DR

A pilot study tested a brain and nerve stimulation treatment for neuropathic pain in spinal cord injury patients but found no significant pain relief.

## Contribution

This pilot trial explores the use of paired associative stimulation for neuropathic pain in incomplete spinal cord injury patients.

## Key findings

- High-PAS did not provide clinically significant pain relief compared to sham treatment.
- Pain is not a contraindication for high-PAS in rehabilitation.
- Further investigation is needed for high-PAS targeting sensory tracts.

## Abstract

Prospective interventional sham-controlled pilot study.

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.

BioMag Laboratory, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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.

Clinically significant relief in pain was not achieved with high-PAS or sham treatment.

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.

clinicaltrials.gov, ID NCT05362422

## Linked entities

- **Diseases:** spinal cord injury (MONDO:0043797)

## Full-text entities

- **Diseases:** Anxiety Symptom (MESH:D001008), motor deficits (MESH:D009461), Disabilities of the Arm, Shoulder and Hand (MESH:D012019), allodynia (MESH:D006930), SCI (MESH:D013119), Spinal Cord Injury Impairment (MESH:D013118), QST (MESH:D013736), deficiencies in muscle strength and hand function (MESH:D009135), Neuropathic pain (MESH:D009437), brain contusion (MESH:D000070624), Spinal Injury (MESH:D013124), Chronic pain (MESH:D059350), depressive symptoms (MESH:D003866), haemorrhage (MESH:D006470), nerve root damage (MESH:D011843), AIS (MESH:D013734), anxiety (MESH:D001007), HUS (MESH:D006463), sensory deficits (MESH:D012678), post (MESH:D000094025), brain injury (MESH:D001930), Pain (MESH:D010146), spasticity (MESH:D009128), injury (MESH:D014947), inflammatory (MESH:D007249), epilepsy (MESH:D004827), withdrawal symptoms (MESH:D013375)
- **Chemicals:** gamma-aminobutyric acid (MESH:D005680), buprenorphine (MESH:D002047), gabapentin (MESH:D000077206), MP (MESH:C063925), duloxetine (MESH:D000068736), gabapentinoids (-), pregabalin (MESH:D000069583), PAS (MESH:D011478)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12957355