Accelerated intermittent theta burst transcranial magnetic stimulation of the dorsolateral prefrontal cortex for chronic knee osteoarthritis pain

Abstract

OBJECTIVE: This study assessed feasibility, safety, and tolerability of accelerated intermittent theta burst stimulation (aiTBS) with effective connectivity-guidance targeting the left dorsolateral prefrontal cortex (lDLPFC) from the right anterior insular (rAI) in chronic knee osteoarthritis pain. METHODS: The BoostCPM clinical trial (ISRCTN15404076) was a randomized, sham-controlled, single-blind, parallel-group pilot study in patients with mild-moderate chronic pain. Participants were assigned 2:1 (active: sham) aiTBS for 4 consecutive days (totaling 36,000 pulses) at a daily dose of 9000 pulses (5 sessions of 1800 pulses). Primary outcomes included safety, tolerability, pain-related and affective outcomes, and quantitative sensory testing. RESULTS: 45 participants received active (n = 33) or sham (n = 12) aiTBS. No serious adverse events were recorded, and protocol adherence (tolerability) was 80.6 % and 100 % for active and sham. Follow-up response rate was 78.1 % and overall acceptance/satisfaction was 89 %. Pain relief was observed immediately after treatment and lasted 16 weeks with clinically meaningful reduction of pain burden, but no differences between groups. CONCLUSIONS: aiTBS with rAI-connected lDLPFC targeting is a safe, well tolerated, feasible, and acceptable intervention in chronic pain patients. However, we found no additional improvements compared to sham. SIGNIFICANCE: Further studies of aiTBS and lDLPFC targeting for pain relief are warranted.