Neuropharmacological basis of rTMS-induced analgesia: The role of endogenous opioids

Abstract

We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, double-blind crossover design, in healthy volunteers. Three groups of 12 volunteers were selected at random and given active stimulation (frequency 10Hz, at 80% motor threshold intensity, 1500 pulses per session) of the right M1, active stimulation of the right DLPFC, or sham stimulation, during two experimental sessions 2 weeks apart. Cold pain thresholds and the intensity of pain induced by a series of fixed-temperature cold stimuli (5, 10, and 15°C) were used to evaluate the analgesic effects of rTMS. Measurements were made at the left thenar eminence, before and 1 hour after the intravenous injection of naloxone (bolus of 0.1mg/kg followed by a continuous infusion of 0.1mg/kg/h until the end of rTMS) or placebo (saline). Naloxone injection significantly decreased the analgesic effects of M1 stimulation, but did not change the effects of rTMS of the DLPFC or sham rTMS. This study demonstrates, for the first time, the involvement of endogenous opioid systems in rTMS-induced analgesia. The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms. Endogenous opioids are shown to be involved in the analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex.

Into the Island: A new technique of non-invasive cortical stimulation of the insula

“…This finding has not been described after either real or sham high-frequency stimulation to M1, PFC, or the primary sensory cortex [5]. This may be related to changes in thermal homeostatic changes caused by the rTMS stimulation on the posterior insula [2].…”

“…A specific nucleus of the spinothalamic tract going from lamina I in the spinal cord to the posterior part of the ventral medial nucleus of the thalamus (VMpo) that projects to the posterior insula in a somatotopically organized fashion, has been described [1,2]. The role of the PICO in the integration of somatosensory and pain inputs has been suggested in a huge number of studies [5,9]. A recent study also showed that in this region the threshold to trigger painful stimulations is lower than in the more rostral regions [14].…”

Interhemispheric Dorsolateral Prefrontal Cortex Connectivity is Associated with Individual Differences in Pain Sensitivity in Healthy Controls

“…Much of this research, however, has focused on the modulatory action of the DLPFC in relation to ipsilateral regions. More recently, studies utilizing noninvasive brain stimulation have suggested that interhemispheric DLPFC connectivity may also be uniquely involved in pain processing (de Andrade et al, 2011;Graff-Guerrero et al, 2005). The present study sought to examine transcallosal DLPFC connectivity during the processing of painful stimuli and to determine whether this connectivity is associated with individual differences in suprathreshold pain sensitivity.…”

Effect of Repetitive Transcranial Magnetic Stimulation on Malignant Visceral Pain

“…Upregulation of motor cortex excitability might therefore modulate pain perception through indirect effects on neural networks in pain-modulating areas, such as thalamic nuclei, as suggested by neuroimaging [5]. The effect on pain may also be mediated by changes in beta-endorphin levels, which have been reported to be increased after repetitive transcranial magnetic stimulation (rTMS) as measured directly in serum as in the studies of de Andrade et al [8] and Ahmed et al [9] or indirectly as in the study of Taylor et al [10] who found that naloxone pretreatment could reduce the analgesic effect of rTMS, consistent with involvement of beta-endorphin.…”