Anticipatory brainstem activity predicts neural processing of pain in humans
ABSTRACT Previous neuroimaging studies have shown brain activity during not only the application of noxious stimuli, but also prior to stimulation. The functional significance of the anticipatory response, however, has yet to be explored. Two theoretical responses involve either a decrease or an increase in sensitivity of the nociceptive system. In a functional magnetic resonance imaging (fMRI) study, brainstem responses during anticipation and processing of thermal noxious stimuli were investigated. Twelve healthy subjects were warned prior to and then received noxious stimulation to their left hand. Behavioral data showed a positive correlation between the intensity of anticipation and pain. FMRI data revealed brainstem activation in the PAG during the anticipation period. When correlated with individual anticipation ratings, activation during anticipation included significant clusters within the entorhinal cortex and ventral tegmental area (VTA). During receipt, activation within the brainstem included the PAG, VTA, rostral ventromedial medulla (RVM), and the parabrachial nucleus (PB), all elements of descending pain pathways. Using a backward model approach, we explored the functional significance of the anticipatory neural response for subsequent pain processing. Results of this regression analysis revealed that insula activity during receipt was predicted by activity in both the entorhinal cortex and VTA during anticipation. We suggest that activation in both regions before and during pain may underlie anticipation and subsequent pain modulatory responses, possibly involving the appraisal and control of attention necessary for pain modulation. Together, the results suggest a possible role of brainstem areas in anticipatory mechanisms involved in the maintenance of chronic pain.
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ABSTRACT: To evaluate the effect of aerobic exercise on perceptual and cerebro-spinal responses to graded electrocutaneous stimuli. The design comprised 2 x 30 min of cycling exercise at 30% and 70% of peak oxygen consumption (VO2 peak) on separate occasions in a counter-balanced order in 10 healthy participants. Assessment of nociceptive withdrawal reflex threshold (NWR-T), pain threshold (PT), and somatosensory evoked potentials (SEPs) to graded electrocutaneous stimuli were performed before and after exercise. Perceptual magnitude ratings and SEPs were compared at 30%PT, 60%PT, 100%PT before (Pre), 5 min after (Post1), and 15 min after (Post2) aerobic exercise. There was no difference in the NWR-T and the PT following exercise at 30% and 70% of VO2 peak. ANOVA for the perceptual response within pooled electrocutaneous stimuli show a significant main effect for time (F2,18=5.41, P=0.01) but no difference for exercise intensity (F1,9=0.02, P=0.88). Within-subject contrasts reveal trend differences between 30%PT and 100%PT for Pre-Post1 (P=0.09) and Pre-Post2 (P=0.02). ANOVA for the SEPs peak-to-peak signal amplitude (N1-P1) show significant main effect for time (F2,18=4.04, P=0.04) but no difference for exercise intensity (F1,9=1.83, P=0.21). Pairwise comparisons for time reveal differences between Pre-Post1 (P=0.06) and Pre-Post2 (P=0.01). There was a significant interaction for SEPs N1-P1 between exercise intensity and stimulus intensity (F2,18=3.56, P=0.05). These results indicate that aerobic exercise did not increase the electrocutaneous threshold for pain and the NWR-T. Aerobic exercise attenuated perceptual responses to innocuous stimuli and SEPs N1-P1 response to noxious stimuli.
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ABSTRACT: The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a "behavioral control" paradigm, which involves the ability to terminate a noxious stimulus, and a "safety signaling" paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.PLoS ONE 12/2014; 9(12):e110654. DOI:10.1371/journal.pone.0110654 · 3.53 Impact Factor
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ABSTRACT: Although somatosensory amplification is theorized to serve a critical role in somatization, it remains poorly understood neurobiologically. In this perspective article, convergent visceral-somatic processing is highlighted, and neuroimaging studies in somatoform disorders are reviewed. Neural correlates of cognitive-affective amplifiers are integrated into a neurocircuit framework for somatosensory amplification. The anterior cingulate cortex, insula, amygdala, hippocampal formation, and striatum are some of the identified regions. Clinical symptomatology in a given patient or group may represent dysfunction in one or more of these neurobehavioral nodes. Somatosensory amplification may, in part, develop through stress-mediated aberrant neuroplastic changes and the neuromodulatory effects of inflammation.The Journal of neuropsychiatry and clinical neurosciences 01/2015; 27(1):e40-50. DOI:10.1176/appi.neuropsych.13070170 · 2.34 Impact Factor