Double-Cone Coil TMS Stimulation of the Medial Cortex Inhibits Central Pain Habituation

Abstract

Objective: The aim of this study was to investigate whether Transcranial Magnetic Stimulation (TMS) applied over the medial line of the scalp affects the subjective perception of continuous pain induced by means of electric stimulation. In addition, we wanted to identify the point of stimulation where this effect was maximum.

Methods: Superficial electrical stimulation was used to induce continuous pain on the dominant hand. At the beginning of the experiment we reached a pain rating of 5 on an 11-point numeric rating scale (NRS; 0 = no pain and 10 = maximum tolerable pain) for each subject by setting individually the current intensity. The TMS (five pulses at increasing intensities) was applied on 5 equidistant points (one per session) over the medial line of the scalp in 13 healthy volunteers using a double-cone coil to stimulate underlying parts of the brain cortex. In every experimental session the painful stimulation lasted 45 minutes, during which pain and distress intensities NRS were recorded continuously. We calculated the effect of adaptation and the immediate effect of the TMS stimulation for all locations. Additionally, an ALE (Activation Likelihood Estimation) meta-analysis was performed to compare our results with the neuroimaging literature on subjective pain rating.

Results: TMS stimulation temporarily decreased the pain ratings, and pain adaptation was suppressed when applying the TMS over the FCz site on the scalp. No effect was found for distress ratings.

Conclusions: The present data suggest that the medial cortex in proximity of the cingulated gyrus has a causal role in adaptation mechanisms and in processing ongoing pain and subjective sensation of pain intensity.

Fig 1. Slope of regression lines for pain and distress ratings, for all stimulation sites and baseline.

Asterisks mark significant regressions and error bars represent standard errors.

Fig 2. Time series of pain ratings for different experimental sessions: baseline, FCz and other stimulation sites (AFz, Fz, Cz, Cpz).

Fig 3. Consistent cingulate ALE cluster, p < 0.05, FDR corrected for multiple comparisons.

Ke = cluster extension > 1000 mm³. The location of 10–10 EEG medial points AFz, Fz, FCz, Cz and CPz are shown along with their projections. The ALE cluster was under the FCz point, in the MCC. Clusters were overlaid onto a sagittal slice of an MNI atlas (x = 4 mm) using the software Mango, version 3.2.1 (http://ric.uthscsa.edu/mango).