Featured Journal Club Article

Sessions of prolonged continuous theta burst stimulation or high-frequency 10 Hz stimulation to the left dorsolateral prefrontal cortex for three days decreased pain sensitivity by modulation of the efficacy of conditioned pain modulation
Enrico De Martino, net al

The 10 Hz repetitive transcranial magnetic stimulation (10 Hz-rTMS) to the left dorsolateral prefrontal cortex produces analgesia, probably by activating the pain modulation system. A newer rTMS paradigm, called theta burst stimulation (TBS), has been developed. Unlike 10 Hz-rTMS, prolonged continuous TBS (pcTBS) mimics endogenous theta rhythms, which can improve induction of synaptic long-term potentiation. Therefore, this study investigated whether pcTBS to the left dorsolateral prefrontal cortex reduced pain sensitivity more efficiently compared with 10 Hz-rTMS, the analgesic effects lasted beyond the stimulation period, and the reduced pain sensitivity was associated with increased efficacy of conditioned pain modulation (CPM) and/or intracortical excitability. Sixteen subjects participated in a randomized cross-over study with pcTBS and 10 Hz-rTMS. Pain thresholds to heat (HPT), cold, pressure (PPT), intracortical excitability assessment, and CPM with mechanical and heat supra-pain threshold test stimuli and the cold pressor test as conditioning were collected before (Baseline), 3 (Day3) and 4 days (Day4) after 3-day session of rTMS. HPTs and PPTs increased with 10 Hz-rTMS and pcTBS at Day3 and Day4 compared with Baseline (P = .007). Based on pooled data from pcTBS and 10 Hz-rTMS, the increased PPTs correlated with increased efficacy of CPM at Day3 (P = .008), while no correlations were found at Day4 or with the intracortical excitability.

Use the following questions to start a discussion about this article at your next journal club meeting.

  1. In this study, 3-daily sessions of left DLPFC rTMS have been selected to modulate pain thresholds, cortical excitability and conditioned pain modulation. Which other cortical areas can be stimulated to obtain analgesic effects? Discuss the role of the left DLPFC on pain modulation and pain suppression.
  2. In this study, there is no procedure of pure sham control because the study question concerned the performance of pcTBS versus the current standard 10 Hz rTMS, rather than versus sham. Here, sham stimulations were inserted within the two active stimulation arms so that all treatment sessions had the same duration and coil stimulation-related sounds. Please discuss the advantages and disadvantages of this study design.
  3. Several complementary mechanisms associated with pain relief by rTMS to left DLPFC have not been investigated in the current study, such as reward, emotion, sympathetic and parasympathetic activity. Please discuss and propose what specific studies are needed to investigate potential changes in these mechanisms.
  4. The potential clinical interest of this technique is the application to control high pain intensity before, during or following surgery or acute injury by decreasing pain sensitivity. It is well known that high pain intensity appears to be one of the strongest predictors of chronic pain development. Please propose and discuss clinical situations in which this application may be used to boost the pain threshold before or immediately after a painful medical procedure or acute injury.
  5. Opioid and pain-relief prescriptions have increased worldwide, despite limited evidence regarding their long-term effectiveness and potential side effects. Discuss the potential clinical application of repetitive TMS, or other neuromodulation techniques, to manage pain.
  6. Analogous to what has been recently proven for the treatment of major depression, one of the significant advantages to using theta-burst stimulation (TBS) is that treatment sessions (including setup) take about 5–10 min, compared with about 45 min for standard 10 Hz rTMS or other neuromodulation techniques. Please discuss the practical advantages of this technique in clinical settings and the importance to develop new technology/stimulation paradigms to improve neuromodulation.

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