EVALUATION COMMITTEE

The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture: 

• Prof. Michael Nitsche, Research Centre for Working Environment and Human Factors, Dortmund, Germany.
• Dr. Aleksandra Vučković, University of Glasgow, Glasgow, UK.
• Dr. Steffen Frahm, HST, Aalborg University, Denmark (Chairman).

Moderator:
Prof. Thomas Graven-Nielsen, HST, Aalborg University

ABSTRACT

Chronic pain conditions pose an immense societal problem, being a leading cause of disability globally and severely impacting the patients’ quality of life. The existing pain management options are insufficient, with only 40-60% of patients experiencing a favourable outcome from pharmacological treatments, which motivates the search for new therapeutic methods to alleviate pain conditions. High-definition transcranial direct current stimulation (HD-tDCS) has shown analgesic efficacy in a number of chronic pain conditions, but the modulatory effects are not fully elucidated, and systematic research in controlled settings is necessary.

The aim of the present thesis was to investigate the modulatory potential of HD-tDCS on the somatosensory system in healthy humans. Two double-blinded sham-controlled experiments were designed and conducted on healthy subjects. Experiment I investigated the effects of three different active HD-tDCS protocols compared to Sham-tDCS (N=20 in each group) on peripheral somatosensory-and pain detection thresholds assessed through a battery of quantitative sensory testing applied over three days (QST). Experiment II investigated the effects of multifocal HD-tDCS compared to Sham-tDCS on experimental pain and hyperalgesia maintained for three days. Somatosensory-and pain detection thresholds, as well as hyperalgesia, were assessed on each day following provocation of experimental pain (injection of nerve growth factor into the right-hand muscle). Concurrently with the peripheral somatosensory testing, the central pain mechanisms (temporal summation of pain and conditioned pain modulation) were assessed in both studies. The effects of HD-tDCS on the central pain mechanisms were compared between the two studies, which constituted the subject of Study III.

In Study I, none of the three active HD-tDCS protocols induced significant changes in detection or pain thresholds compared with the Sham-tDCS. This led to the conclusion that healthy subjects respond differently to tDCS than chronic pain patients have previously been shown to respond.

In Study II, the experimental pain model successfully induced sustained hyperalgesia and pain in both the group that received active HD-tDCS and the group that received Sham-tDCS. The HD-tDCS did not modulate the perceived experimental pain intensity. The active stimulation did, however, delay the establishment of hyperalgesia, although not consistently in all outcome parameters. This led to the conclusion that the effects of the HD-tDCS following experimental persistent pain provocation are more similar to the ones seen in healthy subjects than the analgesic effects shown in chronic pain patients.

In Study III, the experimental prolonged pain model facilitated TSP but did not perturb the cuff-pressure pain sensitivity or CPM. The active HD-tDCS inhibited the pain-related facilitation of TSP compared to Sham-tDCS, suggesting that the efficacy of HD-tDCS might be linked with the presence of sensitized central pain mechanisms.

Overall, HD-tDCS did not modulate the somatosensory pain and detection thresholds but was able to delay the establishment of hyperalgesia and modulate endogenous pain facilitatory mechanisms in healthy subjects with pain-perturbed nervous systems. This indicates that the modulation of the somatosensory system effects may be driven by changes in the pro-nociceptive pain processing mechanisms. When taken together, the findings from the three studies suggest that the effects of HD-tDCS are highly dependent on the state of the central nervous system.