• Onur Annak, Tonio Heidegger, Carmen Walter, Ralf Deichmann, Ulrike Nöth, Onno Hansen-Goos, Ulf Ziemann, and Jörn Lötsch.
• Institute of Clinical Pharmacology, Goethe University, Frankfurt, Germany.
• Pain. 2019 Jan 1; 160 (1): 172-186.

AbstractNoninvasive 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.

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