Robert C. Coghill

Neural correlates of interindividual differences in the subjective experience of pain

Some individuals claim that they are very sensitive to pain, whereas others say that they tolerate pain well. Yet, it is difficult to determine whether such subjective reports reflect true interindividual experiential differences. Using psychophysical ratings to define pain sensitivity and functional magnetic resonance imaging to assess brain activity, we found that highly sensitive individuals exhibited more frequent and more robust pain-induced activation of the primary somatosensory cortex, anterior cingulate cortex, and prefrontal cortex than did insensitive individuals. By identifying objective neural correlates of subjective differences, these findings validate the utility of introspection and subjective reporting as a means of communicating a first-person experience.

Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain

&NA; The oxygen‐15 water bolus positron emission tomography (PET) method was used to image regional brain activity in 4 patients with chronic post‐traumatic neuropathic pain confined to one lower limb and in 1 patient with post‐herpetic neuralgia. In comparison to 13 normal subjects, scans of the patients disclosed a statistically significant decrease in thalamic activity contralateral to the symptomatic side. Examination of the right/left ratio for all the subjects showed that the values for the patients fell at the extremes of the normal range, according to the side of the affected body part. These initial observations suggest that functional alterations in thalamic pain processing circuits may be an important component of chronic neuropathic pain.

Brain Mechanisms Supporting the Modulation of Pain by Mindfulness Meditation

The subjective experience of ones 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.

Multifactorial Preoperative Predictors for Postcesarean Section Pain and Analgesic Requirement

Background: The study aimed to determine predictive factors for postcesarean pain and analgesia using an assessment of pain threshold and suprathreshold thermal stimuli as well as degree of somatization and anxiety. Methods: Thirty-four healthy parturients scheduled for cesarean delivery under subarachnoid anesthesia were enrolled. Preoperative thermal pain threshold, intensity, and unpleasantness to heat stimuli applied to arm and lower back, State Trait Anxiety Inventory, and patient expectation for postoperative pain and need for analgesia were assessed. After surgery, overall, resting, and movement pain and analgesic consumption were recorded. Prediction of pain and analgesic use outcomes was made by principal component factor analysis, followed by stepwise linear regression. Results: Resting pain was predicted by two factors, thermal pain and unpleasantness and patient expectation (r2 = 0.26, P < 0.01), evoked pain by thermal pain threshold in the back (r2 = 0.20, P < 0.009), composite pain by thermal pain and unpleasantness and preoperative blood pressure (r2 = 0.28, P < 0.008), intraoperative analgesic need by preexisting pain (r2 = 0.22, P < 0.006), recovery room analgesia by thermal pain threshold and State Trait Anxiety Inventory (r2 = 0.27, P < 0.01), and total analgesic need by State Trait Anxiety Inventory (r2 = 0.22, P < 0.01). These models predicted the upper twentieth percentile of composite pain scores and analgesic requirement with sensitivity of 0.71 to 0.80 and specificity of 0.76 to 0.80. Conclusions: The authors’ results suggest a meaningful combination of preoperative patient responses from physical and psychological tests yields a valid multifactorial predictive model for postoperative pain and analgesic requirement with significant improvements over individual predictive variables.

Reproducibility of pain measurement and pain perception

&NA; The reproducibility of both the conscious experience of pain and the reproducibility of psychophysical assessments of pain remain critical, yet poorly characterized factors in pain research and treatment. To assess the reproducibility of both the pain experience and two methods of pain assessment, 15 subjects evaluated experimental heat pain during four weekly sessions. In each session, both brief (5 s) and prolonged (90 s) heat stimuli were utilized to determine effects of stimulus duration on reproducibility. Multiple presentations of the brief heat stimuli in each session were used to evaluate effects of response averaging. Both visual analog scales (VAS) and randomized verbal descriptor scales (VDS) were employed to better distinguish variations in the pain experience from variations in pain scale usage. Subjects also rated the intensity of visual stimuli in order to provide an independent assessment of the session‐to‐session variation in the use of both types of scales. Within‐subjects analyses revealed that ratings of visual stimuli exhibited significantly less session‐to‐session variation than ratings of heat pain. Thus, pain perceptions were more variable than perceptions of visual stimuli after controlling for session‐to‐session variations in scale usage. Comparisons between scales indicated that intensity ratings acquired with the VAS had significantly smaller session‐to‐session variation than those acquired with the VDS, although VDS ratings were spread across a larger range of the scale. For both scales, analyses of the effects of stimulus averaging and stimulus duration revealed that averaging multiple assessments of the same stimulus substantially reduces session‐to‐session variation and that multiple assessments of brief stimuli produce responses which are more reproducible than a single presentation of a prolonged stimulus. However, the VAS was significantly more sensitive to small differences in perceived pain intensity and pain unpleasantness, and did not exhibit some of the order effects present with the VDS. Taken together, these results indicate that the reproducibility of psychophysical ratings of pain can be maximized: (1) by averaging responses to multiple, brief stimuli; (2) by providing subjects with a training period distinct from the study period; and (3) by ensuring that interpretation of scale parameters remains constant over time. Thus, although the experiences of both experimental and clinical pain are highly variable, pain assessment procedures can be structured to minimize session‐to‐session variability.

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

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.

Mindfulness meditation-related pain relief: evidence for unique brain mechanisms in the regulation of pain.

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain.

Brain Mechanisms Supporting Spatial Discrimination of Pain

Pain is a uniquely individual experience that is heavily shaped by evaluation and judgments about afferent sensory information. In visual, auditory, and tactile sensory modalities, evaluation of afferent information engages brain regions outside of the primary sensory cortices. In contrast, evaluation of sensory features of noxious information has long been thought to be accomplished by the primary somatosensory cortex and other structures associated with the lateral pain system. Using functional magnetic resonance imaging and a delayed match-to-sample task, we show that the prefrontal cortex, anterior cingulate cortex, posterior parietal cortex, thalamus, and caudate are engaged during evaluation of the spatial locations of noxious stimuli. Thus, brain mechanisms supporting discrimination of sensory features of pain extend far beyond the somatosensory cortices and involve frontal regions traditionally associated with affective processing and the medial pain system. These frontoparietal interactions are similar to those involved in the processing of innocuous information and may be critically involved in placing afferent sensory information into a personal historical context.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis.

Background  Little is known about brain mechanisms supporting the experience of chronic puritus in disease states.

Lesions Limited to the Human Thalamic Principal Somatosensory Nucleus (Ventral Caudal) Are Associated with Loss of Cold Sensations and Central Pain

Central pain is neuropathic pain resulting from a lesion of the CNS, such as a stroke [poststroke central pain (CPSP)]. Lesions involving the posterior thalamus lead to reduction or loss of sensation and to CPSP, although the responsible nuclei have not been identified. We now examine the hypotheses that thalamic lesions must extend posterior to the ventral caudal nucleus (Vc) and include ventral medial posterior nucleus (VMpo), to result in loss of cold sensibility and CPSP. Patients with small thalamic strokes associated with CPSP were evaluated by atlas-based mapping of magnetic resonance imaging scans, and by somatosensory testing. All lesions involved posterior Vc; two lesions also involved nuclei posterior to Vc, but not VMpo. All patients tested had alterations of cold pain sensation and tactile sensation, as measured by von Frey hairs. Three patients had altered cool sensation, and the patient with the least involvement of Vc had normal cool thresholds, suggesting that a critical volume of Vc must be involved before cool sensation is impaired. Perception of warm was impaired only in lesions involving nuclei posterior to Vc. Heat pain perception was never affected. In a subject with cold allodynia, a single-subject protocol PET study measured the responses to immersion of either hand in a 20°C waterbath. The scan during stimulation of the affected hand was characterized by intense activation of contralateral sensorimotor cortex. Therefore, there are modality-specific subnuclear structures in the posterior thalamus, but lesions of Vc not involving VMpo are sufficient to impair cold sensibility and to produce CPSP.