Neuroimaging of the human visceral pain system—A methodological review

Abstract

During the last decades there has been a tremendous development of non-invasive methods for assessment of brain activity following visceral pain. Improved methods for neurophysiological and brain imaging techniques have vastly increased our understanding of the central processing of gastrointestinal sensation and pain in both healthy volunteers as well as in patients suffering from gastrointestinal disorders. The techniques used are functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalography (EEG)/evoked brain potentials (EPs), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), and the multimodal combinations of these techniques. The use of these techniques has brought new insight into the complex brain processes underlying pain perception, including a number of subcortical and cortical regions, and paved new ways in our understanding of acute and chronic pain. The pathways are dynamic with a delicate balance between facilitatory and inhibitory pain mechanisms, and with modulation of the response to internal or external stressors with a high degree of plasticity. Hence, the ultimate goal in imaging of pain is to follow the stimulus response throughout the neuraxis. Brain activity measured by fMRI is based on subtracting regional changes in blood oxygenation during a resting condition from the signal during a stimulus condition, and has high spatial resolution but low temporal resolution. SPECT and PET are nuclear imaging techniques where radiolabeled molecules are injected with visualization of the distribution, density and activity of receptors in the brain allowing not only assessment of brain activity but also study of receptor sites. EEG is based on assessment of electrical activity in the brain, and recordings of the resting EEG and evoked potentials following an external stimulus are used to study normal visceral pain processing, alterations of pain processing in different patient groups and the effect of pharmacological intervention. EEG has high temporal resolution, but relative poor spatial resolution, which however to some extent can be overcome by applying inverse modelling algorithms and signal decomposition procedures. MEG is based on recording the magnetic fields produced by electrical currents in the brain, has high spatial resolution and is especially suitable for the study cortical activation. The treatment of chronic abdominal pain is often ineffective and dissapointing, which leads to search for optimized treatment achieved on the basis of a better understanding of underlying pain mechanisms. Application of the recent improvements in neuroimaging on the visceral pain system may likely in near future contribute substantially to our understanding of the functional and structural pathophysiology underlying chronic visceral pain disorders, and pave the road for optimized individual and mechanism based treatments. The purpose of this review is to give a state-of-the-art overview of these methods, with focus on EEG, and especially the advantages and limitations of the single methods in clinical gastrointestinal pain research including examples from relevant studies.