Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study

Abstract

For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala.

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

“…A study by Moont et al (2011) demonstrated increased activity in the orbitofrontal cortex and amygdala as well as reduced activity in, among others, the anterior cingulate cortex (Moont et al, 2011). The anterior cingulate cortex in particular is frequently involved in modulation of pain and analgesia (Willoch et al, 2003;Sprenger et al, 2011), and a coupling between this brain structure and the descending pain control system has been demonstrated to be modulated by the opioid antagonist naloxone in humans (Sprenger et al, 2011).…”

Significance of Non-phase Locked Oscillatory Brain Activity in Response to Noxious Stimuli

“…5 Human electroencephalographic (EEG) recording studies together with source localization analysis of generators have: i) confirmed the presence and sub-second activation pattern of brain structures tied to pain intensity processing, 6 ii) shown that individual differences in pain sensitivity partly depend on individual differences in the early activation response of the precuneus, 7 iii) demonstrated that the primary somatosensory cortex, when activated soon after a painful stimulus, does indeed participate in the processing of painful experiences, 8 and, iv) shown that regulatory areas of the orbitofrontal cortex and amygdala participate in the initial activation and control of descending bulbo-spinal pain inhibition circuits. 9 Although these studies are useful in their ability to highlight how the human brain responds to painful experiences, they have only considered neuronal networks which oscillate in phase to painful afferent volleys. This type of activity known as evokedor phase locked -can be instructive regarding the role of synchronization in post-stimulus EEG amplitude changes (i.e., post-stimulus reorganization of oscillatory neuronal networks).…”

Emotion Regulation of Neuroticism: Emotional Information Processing Related to Psychosomatic State Evaluated by Electroencephalography and Exact Low-Resolution Brain Electromagnetic Tomography

“…Third, LORETA has low spatial resolution. Although this might make it difficult to visualize the activity of really small and deep structures, such as the amygdala, Moont et al [47] reported activation of the amygdala in their EEG study about the conditioned pain modulation effect using LORETA analysis. We suggest that LORETA also could depict CSD in the amygdala in our study.…”