Effects of continuous theta-burst stimulation of the primary motor and secondary somatosensory areas on the central processing and the perception of trigeminal nociceptive input in healthy volunteers

Pain. 2019 Jan;160(1):172-186. doi: 10.1097/j.pain.0000000000001393.


Noninvasive modulation of the activity of pain-related brain regions by means of transcranial magnetic stimulation promises an innovative approach at analgesic treatments. However, heterogeneous successes in pain modulation by setting reversible "virtual lesions" at different brain areas point at unresolved problems including the optimum stimulation site. The secondary somatosensory cortex (S2) has been previously identified to be involved in the perception of pain-intensity differences. Therefore, impeding its activity should impede the coding of the sensory component of pain intensity, resulting in a flattening of the relationship between pain intensity and physical stimulus strength. This was assessed using inactivating spaced continuous theta-burst stimulation (cTBS) in 18 healthy volunteers. In addition, cTBS was applied on the primary motor cortex (M1) shown previously to yield moderate and variable analgesic effects, whereas sham stimulation at both sites served as placebo condition. Continuous theta-burst stimulation flattened the relationship between brain activation and stimulus strength, mainly at S2, the insular cortex, and the postcentral gyrus (16 subjects analyzed). However, these effects were observed after inactivation of M1 while this effect was not observed after inactivation of S2. Nevertheless, both the M1 and the S2-spaced cTBS treatment were not reflected in the ratings of the nociceptive stimuli of different strengths (17 subjects analyzed), contrasting with the clear coding of stimulus strength by these data. Hence, while modulating the central processing of nociceptive input, cTBS failed to produce subjectively relevant changes in pain perception, indicating that the method in the present implementation is still unsuitable for clinical application.

MeSH terms

  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Evoked Potentials, Motor / physiology*
  • Female
  • Healthy Volunteers
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Motor Cortex / diagnostic imaging
  • Motor Cortex / physiology*
  • Oxygen / blood
  • Pain / diagnostic imaging
  • Pain / etiology
  • Pain / pathology*
  • Pain Perception / physiology*
  • Somatosensory Cortex / diagnostic imaging
  • Somatosensory Cortex / physiology*
  • Theta Rhythm / physiology*
  • Transcranial Magnetic Stimulation
  • Young Adult


  • Oxygen