Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

We review recent advances in brain imaging in humans, concentrating on advances in our understanding of the human brain in clinical chronic pain. Understanding regarding anatomical and functional reorganization of the brain in chronic pain is emphasized. We conclude by proposing a brain model for the transition of the human from acute to chronic pain.

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Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain

The subjective experience of one's environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events. To better understand how meditation influences the sensory experience, we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After 4 d of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57% and pain intensity ratings by 40% when compared to rest. A two-factor repeated-measures ANOVA was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contralateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas. Together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information.

https://www.jneurosci.org/content/jneuro/31/14/5540.full.pdf

Brain Mechanisms Supporting the Modulation of Pain by Mindfulness Meditation

Pain is a conscious experience, crucial for survival. To investigate the neural basis of pain perception in humans, a large number of investigators apply noxious stimuli to the body of volunteers while sampling brain activity using different functional neuroimaging techniques. These responses have been shown to originate from an extensive network of brain regions, which has been christened the Pain Matrix and is often considered to represent a unique cerebral signature for pain perception. As a consequence, the Pain Matrix is often used to understand the neural mechanisms of pain in health and disease. Because the interpretation of a great number of experimental studies relies on the assumption that the brain responses elicited by nociceptive stimuli reflect the activity of a cortical network that is at least partially specific for pain, it appears crucial to ascertain whether this notion is supported by unequivocal experimental evidence. Here, we will review the original concept of the "Neuromatrix" as it was initially proposed by Melzack and its subsequent transformation into a pain-specific matrix. Through a critical discussion of the evidence in favor and against this concept of pain specificity, we show that the fraction of the neuronal activity measured using currently available macroscopic functional neuroimaging techniques (e.g., EEG, MEG, fMRI, PET) in response to transient nociceptive stimulation is likely to be largely unspecific for nociception.

From the neuromatrix to the pain matrix (and back).

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(14)00217-3.pdf

The dynamic pain connectome

Subjective sensory experiences are constructed by the integration of afferent sensory information with information about the uniquely personal internal cognitive state The insular cortex is anatomically positioned to serve as one potential interface between afferent processing mechanisms and more cognitively oriented modulatory systems However, the role of the insular cortex in such modulatory processes remains poorly understood Two individuals with extensive lesions to the insula were examined to better understand the contribution of this brain region to the generation of subjective sensory experiences Despite substantial differences in the extent of the damage to the insular cortex, three findings were common to both individuals First, both subjects had substantially higher pain intensity ratings of acute experimental noxious stimuli than age-matched control subjects Second, when pain-related activation of the primary somatosensory cortex was examined during left- and right-sided stimulation, both individuals exhibited dramatically elevated activity of the primary somatosensory cortex ipsilateral to the lesioned insula in relation to healthy control subjects Finally, both individuals retained the ability to evaluate pain despite substantial insular damage and no evidence of detectible insular activity Together, these results indicate that the insula may be importantly involved in tuning cortical regions to appropriately use previous cognitive information during afferent processing Finally, these data suggest that a subjectively available experience of pain can be instantiated by brain mechanisms that do not require the insular cortex

https://www.jneurosci.org/content/jneuro/29/9/2684.full.pdf

Roles of the Insular Cortex in the Modulation of Pain: Insights from Brain Lesions

Cerebral cortical activity is heavily influenced by interactions with the basal ganglia. These interactions occur via cortico-basal ganglia-thalamo-cortical loops. The putamen is one of the major sites of cortical input into basal ganglia loops and is frequently activated during pain. This activity has been typically associated with the processing of pain-related motor responses. However, the potential contribution of putamen to the processing of sensory aspects of pain remains poorly characterized. In order to more directly determine if the putamen can contribute to sensory aspects of pain, nine individuals with lesions involving the putamen underwent both psychophysical and functional imaging assessment of perceived pain and pain-related brain activation. These individuals exhibited intact tactile thresholds, but reduced heat pain sensitivity and widespread reductions in pain-related cortical activity in comparison with 14 age-matched healthy subjects. Using magnetic resonance imaging to assess structural connectivity in healthy subjects, we show that portions of the putamen activated during pain are connected not only with cortical regions involved in sensory-motor processing, but also regions involved in attention, memory and affect. Such a framework may allow cognitive information to flow from these brain areas to the putamen where it may be used to influence how nociceptive information is processed. Taken together, these findings indicate that the putamen and the basal ganglia may contribute importantly to the shaping of an individual subjective sensory experience by utilizing internal cognitive information to influence activity of large areas of the cerebral cortex.

The contribution of the putamen to sensory aspects of pain: insights from structural connectivity and brain lesions

Pain is a highly personal experience that varies substantially among individuals In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men) Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49 °C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship No regions showed a positive relationship to pain sensitivity These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure

Christopher J. Starr

Papers

Roles of the Insular Cortex in the Modulation of Pain: Insights from Brain Lesions

The contribution of the putamen to sensory aspects of pain: insights from structural connectivity and brain lesions

Pain sensitivity is inversely related to regional grey matter density in the brain

Psychological and Sensory Predictors of Experimental Thermal Pain: A Multifactorial Model