Chapter

Feeling sick: a combination of bottom-up and top-down events

Fabrizio Benedetti

in The Patient's Brain

Published on behalf of Oxford University Press

Published in print October 2010 | ISBN: 9780199579518
Published online February 2013 | e-ISBN: 9780191754661 | DOI: http://dx.doi.org/10.1093/med/9780199579518.003.0003
Feeling sick: a combination of bottom-up and top-down events

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1) Feeling sick is a complex combination of events that may arise from damaged peripheral tissues as well as from their modulation by psychosocial factors. Therefore, the clinician must consider a symptom not so much as a single and isolated entity, but rather within the psychological and social context of the patient. The mere assessment of peripheral tissue damage considers bottom-up processes only, without taking the top-down modulation into consideration. 2) Interoceptive sensibility is at the very heart of the process of feeling sick. Whereas usually internal organs are not perceived in normal conditions, they may get access to consciousness in particular circumstances. This is due to the activation of receptors that project to a variety of subcortical and cortical regions. For example, several areas of the cerebral cortex are activated by interoceptive stimuli arising from the gastrointestinal and cardiovascular systems. 3) The insular cortex and the anterior cingulate cortex are key regions in interoceptive processing and in awareness. A peculiar feature of these areas in hominoid primates is the presence of clusters of large spindle-shaped neurons among the pyramidal neurons in layer 5, the so-called von Economo neurons. There is a phylogenetic progression of the von Economo neurons. In fact, they are present in adult humans, but progressively decrease in children, gorillas, and chimpanzees, and are completely lacking in macaque monkeys. Some studies have related the insula to agnosognosia, that is, the lack of awareness about a functional impairment, such that agnosognosic patients do not recognize their own illness. 4) Different emotional states, such as anxiety and depression, or different cognitive tasks, like attention and distraction, may have profound effects on interoceptive awareness, such that perceptions can be reported in different ways from time to time, and interoceptive-evoked brain activity may vary in different circumstances. For example, activation within right insular and bilateral dorsal anterior cingulate gyrus during oesophageal stimulation is significantly greater with visual presentation of fearful than neutral faces. 5) Pain is a representative symptom and is better understood compared with other symptoms, like nausea and fatigue. Thus, its study helps us better understand bottom-up processes and top-down modulation. Pain is perceived differently in different individuals and in different circumstances, and these differences are attributable to both psychosocial and genetic factors. In order to understand the pain intensity of his patient, the clinician should assess not only the tissue damage, but also his psychological state. This may uncover possible emotion-induced amplification of pain. 6) The descending pain modulatory network is a complex series of cortical and subcortical regions which are interconnected by different neurochemical pathways, e.g. opioidergic, dopaminergic, serotoninergic. These neurotransmitters may inhibit and/or facilitate pain transmission. 7) Feeling sick does not necessarily mean physical suffering. For example, negative emotions, such as anxiety, may be induced by negative diagnoses of asymptomatic diseases or, otherwise, the subject may realize that the colour of his body is changing, as occurs in jaundice. Negative emotions are important in the process of feeling sick because they modulate the magnitude of a symptom, e.g. pain. 8) Negative emotions are processed in the limbic system and can be studied with both imaging techniques and intraoperative electrical stimulation. The latter is particularly interesting because it shows that the ongoing context is crucial in evoking emotional experiences. For example, the emotional responses in the ventral pole of the subthalamic nucleus can be better described as context-dependent rather that site-dependent. 9) The effect of anxiety on pain is one of the most studied. Anxiety-induced hyperalgesia is mediated, at least in part, by cholecystokinin (CCK). In fact, CCK antagonists can prevent it. In addition, expecting pain may induce both hyperalgesic and allodynic effects, and these are related to the enhancement of several subcortical and cortical areas. In the rostroventromedial medulla there are neurons that contain both CCK and opioid receptors and that might take part in the emotional modulation of pain. 10) Other negative emotions, such as anger and depression, impact on pain perception but the mechanisms are less understood compared with anxiety. The amplifying effect of depressive symptoms on pain is likely to be mediated by a functional deficit of the prefrontal cortex and the descending pain modulatory network. According to this perspective, negative emotions-induced hypo-responsivity of the prefrontal cortex might provide the basis for the aggravation of pain. 11) Overall, the process of feeling sick is an intricate combination of bottom-up and top-down events that eventually initiates the seeking behaviour aimed at suppressing both physical discomfort and negative emotions, as described in the next chapter.

Chapter.  19318 words.  Illustrated.

Subjects: Psychiatry

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