Advancing Transcranial Magnetic Stimulation Methods for Complex Regional Pain Syndrome: An Open-Label Study of Paired Theta Burst and High-Frequency Stimulation

Neuromodulation. 2018 Jun;21(4):409-416. doi: 10.1111/ner.12760. Epub 2018 Mar 4.


Introduction: Complex Regional Pain Syndrome (CRPS), a rare and severe chronic pain condition, often responds poorly to existing treatments. Previous studies demonstrated Transcranial Magnetic Stimulation (TMS) provided short-term pain relief for upper extremity CRPS.

Methods: Building on previous methodologies, we employed a TMS protocol that may lead to significant pain relief for upper and lower extremity CRPS in a nonrandomized open label pilot trial involving 21 participants. We individualized TMS coil positioning over motor cortex of somatic pain location, and administered intermittent theta-burst stimulation followed by 10 Hz high-frequency stimulation using a deeper targeting coil. We assessed response (≥30% pain reduction) from a single session (n = 5) and five consecutive daily sessions (n = 12) and compared change in pain from baseline, after one treatment and one-week posttreatment between groups using a mixed ANVOA.

Results: Both groups demonstrated significant pain reduction after one session and one-week posttreatment; however, no group differences were present. From a single session, 60% of participants responded at Week 1. From five sessions, 58% and 50% of participants responded at Weeks 1 and 2, respectively. Two from each group achieved >50% pain reduction beyond six to eight weeks. No serious adverse events occurred. Though headache and nausea were the most common side-effects, we urge careful monitoring to prevent seizures with this protocol.

Conclusions: We used a TMS protocol that, for the first time, led to significant pain relief in upper and lower extremity CRPS, and will soon examine our protocol in a larger, controlled trial.

Keywords: Complex regional pain syndrome (CRPS); high-frequency stimulation; theta-burst stimulation; transcranial magnetic stimulation (TMS).

MeSH terms

  • Adult
  • Aged
  • Brain Mapping
  • Complex Regional Pain Syndromes / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / physiology*
  • Outcome Assessment, Health Care
  • Pain Measurement
  • Transcranial Magnetic Stimulation / methods*
  • Upper Extremity / physiology
  • Young Adult