Introduction: Spinal Cord Stimulation (SCS) is a successful last-resort treatment for chronic pain patients, although its exact mechanisms of action (MOAs) still need to be unraveled. The MOAs of SCS partly rely on spinal mechanisms (gate control theory) and supraspinal mechanisms likely play a role as well. Pain processing involves a complex network of cortical structures and can be modulated. Conditioned pain modulation (CPM) is a measure to describe the modulation of pain perception. CPM relies on the 'pain inhibits pain' theory, where a nociceptive test stimulus (TS) is modulated by applying a nociceptive conditioning stimulus (CS). CPM is often less efficient in chronic pain patients, but this might be improved by effective SCS.
Objective: The aim of this thesis is to assess how effective SCS affects the supraspinal mechanisms of pain modulation in chronic pain patients. The supraspinal mechanisms are evaluated using magnetoencephalography (MEG) to assess the cortical response to TS before, during and after CPM in chronic pain patients treated with SCS.

Methods: Chronic pain patients treated with SCS underwent MEG sessions after receiving tonic and burst SCS for one week. Each session consisted of three CPM blocks: before, during and after CPM. During each CPM block 22 TS were administered accompanied by CS during CPM, after each block the subject reported a subjective pain rating of TS (and CS). The cortical response to TS, measured using MEG, was analyzed in the time and time-frequency (TF) domain using Brainstorm and Matlab software. TF decomposition was computed in several pain related regions of interest using complex Morlet wavelets. We examined how CPM affected event related spectral perturbations, induced by TS, in the alpha (8-12 Hz) and beta (13-30 Hz) frequency ranges. The average cortical response during tonic and burst SCS was evaluated in all subjects, and separately in the five clearest SCS responders (effective) and the five clearest SCS non-responders (non-effective).
Results: 17 subjects were included. On average a decrease in subjective pain ratings of TS was observed during CPM. In the time domain, TS evoked activity in areas related to the sensory-discriminative aspect of pain. In the TF domain, TS induced event related desynchronization (ERD) followed by event related synchronization (ERS) in the alpha and beta frequency ranges in the bilateral sensorimotor cortices. During CPM the power of beta ERS was significantly decreased during burst SCS. A trend was observed towards a decrease in power of beta ERS for the effective burst SCS group, whereas no decrease was observed for the non-effective burst, effective tonic and non-effective tonic SCS groups.
Conclusion: The results suggest that on average, effective burst SCS decreases the power of beta ERS during CPM, this decrease indicates successful modulation of pain. Therefore, I suggest that effective burst SCS is capable of improving the supraspinal mechanisms of pain modulation, whereas effective tonic SCS is not capable of doing so. This suggestion indicates a partially different MOA for tonic and burst SCS. Future studies containing larger group sizes should validate these findings.