Clinical effects and brain metabolic correlates in non-invasive cortical neuromodulation for visceral pain

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Abstract
Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain. Here we report findings of a phase II, sham-controlled clinical trial assessing the clinical effects and brain metabolic correlates of a 10-day course of daily sessions of slow-frequency, repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary somatosensory cortex (SII) in patients with chronic pancreatitis and severe visceral pain. Our results show a significant reduction in pain after real rTMS that lasted for at least 3 weeks following treatment. These clinical changes were correlated with increases in glutamate and N-acetyl aspartate (NAA) levels--neurometabolites associated with cortical activity and brain damage--as measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS). Adverse effects in the real rTMS group were mild and short-lasting. Our results support preliminary findings showing that modulation of right SII with rTMS is associated with a significant analgesic effect and that this effect is correlated with an increase in excitatory neurotransmitter levels such as glutamate and NAA.

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