Biopsychosocial Aspects of Functional Gastrointestinal Disorders: How Central and Environmental Processes Contribute to the Development and Expression of Functional Gastrointestinal Disorders
2016; Elsevier BV; Volume: 150; Issue: 6 Linguagem: Inglês
10.1053/j.gastro.2016.02.027
ISSN1528-0012
AutoresLukas Van Oudenhove, Rona L. Levy, Michael D. Crowell, Douglas A. Drossman, Albena Halpert, Laurie Keefer, Jeffrey M. Lackner, Tasha Murphy, Bruce D. Naliboff,
Tópico(s)Infant Health and Development
ResumoWe provide a general framework for understanding functional gastrointestinal disorders (FGIDs) from a biopsychosocial perspective. More specifically, we provide an overview of the recent research on how the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of FGIDs. We emphasize that considering and addressing all these factors is a conditio sine qua non for appropriate treatment of these conditions. First, we provide an overview of what is currently known about how each of these factors—the environment, including the influence of those in an individual's family, the individual's own psychological states and traits, and the individual's (neuro)physiological make-up—interact to ultimately result in the generation of FGID symptoms. Second, we provide an overview of commonly used assessment tools that can assist clinicians in obtaining a more comprehensive assessment of these factors in their patients. Finally, the broader perspective outlined earlier is applied to provide an overview of centrally acting treatment strategies, both psychological and pharmacological, which have been shown to be efficacious to treat FGIDs. We provide a general framework for understanding functional gastrointestinal disorders (FGIDs) from a biopsychosocial perspective. More specifically, we provide an overview of the recent research on how the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of FGIDs. We emphasize that considering and addressing all these factors is a conditio sine qua non for appropriate treatment of these conditions. First, we provide an overview of what is currently known about how each of these factors—the environment, including the influence of those in an individual's family, the individual's own psychological states and traits, and the individual's (neuro)physiological make-up—interact to ultimately result in the generation of FGID symptoms. Second, we provide an overview of commonly used assessment tools that can assist clinicians in obtaining a more comprehensive assessment of these factors in their patients. Finally, the broader perspective outlined earlier is applied to provide an overview of centrally acting treatment strategies, both psychological and pharmacological, which have been shown to be efficacious to treat FGIDs. It is generally accepted that functional gastrointestinal disorders (FGIDs) result from complex and reciprocal interactions between biological, psychological, and social factors, rather than from linear monocausal etiopathogenetic processes. This consensus report, based on an extensive critical literature review by a multidisciplinary expert committee, aims to provide a framework for understanding FGID from a biopsychosocial perspective. Further, we emphasize why and how knowledge of this biopsychosocial framework is critical for assessment and treatment of these difficult-to-treat disorders that often induce uncertainty and frustration in caregivers and patients alike. The many processes that are part of these complex interactions of the individual's physiology, psychology, and environment are illustrated in an overview of the biopsychosocial model of FGID (Figure 1) and described further. There is familial aggregation of childhood FGID.1Bode G. Brenner H. Adler G. Rothenbacher D. Recurrent abdominal pain in children: evidence from a population-based study that social and familial factors play a major role but not Helicobacter pylori infection.J Psychosom Res. 2003; 54: 417-421Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar Children of adult irritable bowel syndrome (IBS) patients make more health care visits than the children of non-IBS parents. This pattern is not confined to gastrointestinal (GI) symptoms2Levy R.L. Whitehead W.E. Von Korff M.R. et al.Intergenerational transmission of gastrointestinal illness behavior.Am J Gastroenterol. 2000; 95: 451-456Crossref PubMed Google Scholar and holds for maternal and paternal symptoms.3Walker L.S. Garber J. Greene J.W. Somatization symptoms in pediatric abdominal pain patients: Relation to chronicity of abdominal pain and parent somatization.J Abnorm Child Psychol. 1991; 19: 379-394Crossref PubMed Scopus (158) Google Scholar, 4Walker L.S. Garber J. Greene J.W. Somatic complaints in pediatric patients: a prospective study of the role of negative life events, child social and academic competence, and parental somatic symptoms.J Consult Clin Psychol. 1994; 62: 1213-1221Crossref PubMed Google Scholar Although there is ongoing research into a genetic explanation for these familial patterns, what children learn from parents can make an even greater contribution to the risk for developing an FGID than genetics.5Levy R.L. Jones K.R. Whitehead W.E. et al.Irritable bowel syndrome in twins: Heredity and social learning both contribute to etiology.Gastroenterology. 2001; 121: 799-804Abstract Full Text Full Text PDF PubMed Google Scholar The basic learning principle of positive reinforcement or reward, defined as an event following some behavior that increases the likelihood of that behavior occurring in the future, is a likely contributor to how this can occur. Children whose mothers reinforce illness behavior experience more severe stomachaches and more school absences than other children6Levy R.L. Whitehead W.E. Walker L.S. et al.Increased somatic complaints and health-care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms.Am J Gastroenterol. 2004; 99: 2442-2451Crossref PubMed Scopus (105) Google Scholar (Figure 2). In addition, when parents were asked to show positive or sympathetic responses to their children's pain in a laboratory, the frequency of pain complaints was higher than when parents are instructed to ignore them.7Walker L.S. Williams S.E. Smith C.A. et al.Parent attention versus distraction: impact on symptom complaints by children with and without chronic functional abdominal pain.Pain. 2006; 122: 43-52Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar Finally, a large randomized clinical trial of children with functional abdominal pain found that cognitive-behavioral treatment (CBT) targeting coping strategies, as well as parents' and children's beliefs about, and responses to, children's pain complaints, induced greater baseline to follow-up decreases in pain and GI symptoms compared with an educational intervention controlling for time and attention,8Levy R.L. Langer S. Walker L. et al.Twelve month follow-up of cognitive behavioral therapy for children with functional abdominal pain.JAMA Pediatr. 2013; 167: 178-184Crossref PubMed Scopus (16) Google Scholar and that this effect was mediated by changes in parents' cognitions about their child's pain.9Levy R.L. Langer S.L. Romano J.M. et al.Cognitive mediators of treatment outcomes in pediatric functional abdominal pain.Clin J Pain. 2014; 30: 1033-1043Crossref PubMed Scopus (8) Google Scholar There is also a strong association between parental psychological status, particularly anxiety, depression, and somatization, and children's abdominal symptoms.4Walker L.S. Garber J. Greene J.W. Somatic complaints in pediatric patients: a prospective study of the role of negative life events, child social and academic competence, and parental somatic symptoms.J Consult Clin Psychol. 1994; 62: 1213-1221Crossref PubMed Google Scholar, 10Seino S. Watanabe S. Ito N. et al.Enhanced auditory brainstem response and parental bonding style in children with gastrointestinal symptoms.PLoS One. 2012; 7: e32913Crossref PubMed Scopus (3) Google Scholar, 11Campo J.V. Bridge J. Lucas A. et al.Physical and emotional health of mothers of youth with functional abdominal pain.Arch Pediatr Adolesc Med. 2007; 161: 131-137Crossref PubMed Scopus (74) Google Scholar This association could be occurring through modeling—children observing and learning to display the behaviors they observe, in this case, possibly heightened attention to, or catastrophizing about, somatic sensations. However, the effect of parental traits on children's symptoms could also occur through reinforcement. Parents with certain traits or beliefs, such as excessive worry about pain, might pay more attention to, and thereby reward, somatic complaints. Parents' catastrophizing cognitions about their own pain predicted responses to their children's abdominal pain that encouraged illness behavior, which in turn predicted child functional disability.12Langer S.L. Romano J.M. Levy R.L. et al.Catastrophizing and parental response to child symptom complaints.Child Health Care. 2009; 38: 169-184Crossref PubMed Scopus (27) Google Scholar Compared with controls, IBS patients report a higher prevalence of adverse life events in general, and physical punishment, emotional abuse, and sexual abuse in particular13Bradford K. Shih W. Videlock E.J. et al.Association between early adverse life events and irritable bowel syndrome.Clin Gastroenterol Hepatol. 2012; 10: 385-390Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar; such history is related to FGID severity and clinical outcomes, such as psychological distress, and daily functioning.14Drossman D.A. Abuse, trauma, and GI illness: is there a link?.Am J Gastroenterol. 2011; 106: 14-25Crossref PubMed Scopus (53) Google Scholar This in turn leads to increased health care seeking, which could explain the higher association of abuse histories with GI illness in referral centers compared with primary care.14Drossman D.A. Abuse, trauma, and GI illness: is there a link?.Am J Gastroenterol. 2011; 106: 14-25Crossref PubMed Scopus (53) Google Scholar Population-based studies have led to more conflicting results with regard to the association between self-reported FGIDs and abuse history.15Galli N. The influence of cultural heritage on the health status of Puerto Ricans.J Sch Health. 1975; 45: 10-16Crossref PubMed Google Scholar, 16Quigley E.M. Sperber A.D. Drossman D.A. WGO—Rome foundation joint symposium summary: IBS—the global perspective.J Clin Gastroenterol. 2011; 45: i-iiCrossref PubMed Google Scholar Further, it should be noted that high frequencies of childhood abuse (approaching 50%) are not unique to patients with FGID, as similar figures are found in patients with non-GI functional somatic syndromes (FSS, eg, pelvic pain, headaches, and fibromyalgia).17Murray C.D. Flynn J. Ratcliffe L. et al.Effect of acute physical and psychological stress on gut autonomic innervation in iritable bowel syndrome.Gastroenterology. 2004; 127: 1695-1703Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar The onset of FGIDs has been associated with the experience of severely threatening events, such as the breakup of an intimate relationship. In one study, two-thirds of patients had experienced such an event compared with one-quarter of healthy controls.18Bitton A. Dobkin P.L. Edwardes M.D. et al.Predicting relapse in Crohn's disease: a biopsychosocial model.Gut. 2008; 57: 1386-1392Crossref PubMed Scopus (103) Google Scholar Prospective studies have demonstrated that the experience of stressful life events is associated with symptom exacerbation and frequent health care seeking among adults with IBS.19Lackner J.M. Gurtman M.B. Pain catastrophizing and interpersonal problems: a circumplex analysis of the communal coping model.Pain. 2004; 110: 597-604Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 20Sperber A.D. Drossman D.A. Quigley E. The global perspective on irritable bowel syndrome: a Rome Foundation-World Gastroenterology Organization symposium.Am J Gastroenterol. 2012; 107: 1602-1609Crossref PubMed Scopus (6) Google Scholar Chronic life stress is the main predictor of IBS symptom intensity over 16 months, even after controlling for relevant confounders.21Drossman D.A. Li Z. Leserman J. et al.Effects of coping on health outcome among female patients with gastrointestinal disorders.Psychosom Med. 2000; 62: 309-317Crossref PubMed Google Scholar Finally, stress can affect FGID treatment outcomes—one study demonstrated that the presence of a single stressor within 6 months before participation in an IBS treatment program was directly associated with poor outcomes and higher symptom intensity at 16-month follow-up when compared with patients without exposure to such a stressor.22Bennett E.J. Tennant C.C. Piesse C. et al.Level of chronic life stress predicts clinical outcome in irritable bowel syndrome.Gut. 1998; 43: 256-261Crossref PubMed Google Scholar Quality or lack of social support is related to many aspects of IBS.23Lackner J.M. Gudleski G.D. Firth R. et al.Negative aspects of close relationships are more strongly associated than supportive personal relationships with illness burden of irritable bowel syndrome.J Psychosom Res. 2013; 74: 493-500Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Patients report finding social support as a way to help overcome IBS.24Jakobsson Ung E. Ringstrom G. Sjovall H. et al.How patients with long-term experience of living with irritable bowel syndrome manage illness in daily life: a qualitative study.Eur J Gastroenterol Hepatol. 2013; 25: 1478-1483Crossref PubMed Scopus (1) Google Scholar Relatedly, perceived adequacy of social support is associated with IBS symptom severity, putatively through a reduction in stress levels.25Lackner J.M. Brasel A.M. Quigley B.M. et al.The ties that bind: perceived social support, stress, and IBS in severely affected patients.Neurogastroenterol Motil. 2010; 22: 893-900Crossref PubMed Scopus (21) Google Scholar However, negative social relationships marked by conflict and adverse interactions are more consistently and strongly related to IBS outcomes than social support.23Lackner J.M. Gudleski G.D. Firth R. et al.Negative aspects of close relationships are more strongly associated than supportive personal relationships with illness burden of irritable bowel syndrome.J Psychosom Res. 2013; 74: 493-500Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Illustrative of the role of social support and clinically important, a supportive patient−practitioner relationship significantly improved symptomatology and quality of life in patients with IBS.26Conboy L.A. Macklin E. Kelley J. et al.Which patients improve: characteristics increasing sensitivity to a supportive patient-practitioner relationship.Soc Sci Med. 2010; 70: 479-484Crossref PubMed Scopus (21) Google Scholar Cultural beliefs, norms, and behaviors affect all aspects of what has been discussed in this section: interactions within the family, with other support systems, and the world at large. For more extensive discussion, see the article in this issue regarding multicultural aspects of FGIDs. Psychological distress is an important risk factor for the development of FGIDs and, when present, can perpetuate or exacerbate symptoms. Further, it affects the doctor−patient relationship and negatively impacts treatment outcomes. However, psychological distress can also be a consequence rather than a cause of disease burden. Comorbid anxiety and depression are independent predictors of post-infectious IBS and functional dyspepsia (FD) but, at the same time, also occur as a consequence of bodily symptoms and related quality of life impairment. The absence of formal psychiatric comorbidity does not exclude a role of dysfunctional cognitive and affective processes not captured by the current psychiatric classification system(s) (in the sense of not reaching the threshold for a psychiatric disorder or not being included in the classification system, eg, in the case of symptom-specific anxiety, which is relevant in the context of FGID but does not constitute a psychiatric disorder). Overlap between depression and FGID is about 30% in primary care settings and slightly higher in tertiary care.27Addolorato G. Mirijello A. D'Angelo C. et al.State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting.Int J Clin Pract. 2008; 62: 1063-1069Crossref PubMed Scopus (41) Google Scholar Depression can impact the number of functional GI symptoms experienced or the number of FGID diagnoses.28Bouchoucha M. Hejnar M. Devroede G. et al.Anxiety and depression as markers of multiplicity of sites of functional gastrointestinal disorders: a gender issue?.Clin Res Hepatol Gastroenterol. 2013; 37: 422-430Crossref PubMed Scopus (10) Google Scholar, 29Van Oudenhove L. Vandenberghe J. Vos R. et al.Factors associated with co-morbid irritable bowel syndrome and chronic fatigue-like symptoms in functional dypepsia.Neurogastroenterol Motil. 2011; 23 (524–e202)Google Scholar Suicidal ideation is present in between 15% and 38% of patients with IBS, and has been linked to hopelessness associated with symptom severity, interference with life, and inadequacy of treatment.30Miller V. Hopkins L. Whorwell P.J. Suicidal ideation in patients with irritable bowel syndrome.Clin Gastroenterol Hepatol. 2004; 2: 1064-1068Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Comorbid depression has been linked to poor outcomes, including high health care utilization and cost, functional impairment, poor quality of life, and poor treatment engagement and outcomes.25Lackner J.M. Brasel A.M. Quigley B.M. et al.The ties that bind: perceived social support, stress, and IBS in severely affected patients.Neurogastroenterol Motil. 2010; 22: 893-900Crossref PubMed Scopus (21) Google Scholar, 31Lackner J.M. Gurtman M.B. Patterns of interpersonal problems in irritable bowel syndrome patients: a circumplex analysis.J Psychosom Res. 2005; 58: 523-532Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Anxiety disorders are the most common psychiatric comorbidity, occurring in 30%−50% of FGID patients. They may initiate or perpetuate FGID symptoms through their associated heightened autonomic arousal (in response to stress) or at the level of the brain, which can interfere with GI sensitivity and motor function. Vulnerability to anxiety disorders might share similar pathways as vulnerability to FGIDs, particularly with respect to anxiety sensitivity, body vigilance, and ability to tolerate discomfort. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition discarded the concept of somatization, originally defined as "a tendency to experience and communicate somatic symptoms unaccounted for by pathological findings in response to psychosocial stress and seek medical help for it,"32Lipowski Z.J. Somatization: the concept and its clinical application.Am J Psychiatry. 1988; 145: 1358-1368Crossref PubMed Google Scholar but often operationalized in a descriptive way, measuring somatization by simply quantifying the number of (medically unexplained) symptoms, in favor of somatic symptom disorder.33American Psychiatric AssociationDiagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC2013Crossref Google Scholar In the new diagnostic category, somatic symptoms may or may not be medically unexplained, but are distressing and disabling and associated with excessive and disproportionate thoughts, feelings, and behaviors for more than 6 months.34Dimsdale J.E. Creed F. Escobar J. et al.Somatic symptom disorder: an important change in DSM.J Psychosom Res. 2013; 75: 223-228Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar This approach shifts the experience of medically unexplained symptoms from (unconscious) manifestations of psychological distress toward abnormal cognitive−affective processes (eg, excessive illness worry, body preoccupation, and hypochondriasis), both as contributors to, and consequences of, symptoms.35Duddu V. Isaac M.K. Chaturvedi S.K. Somatization, somatosensory amplification, attribution styles and illness behaviour: a review.Int Rev Psychiatry. 2006; 18: 25-33Crossref PubMed Scopus (82) Google Scholar Somatization is associated with GI sensorimotor processes, including gastric sensitivity and gastric emptying, symptom severity,36Van Oudenhove L. Vandenberghe J. Geeraerts B. et al.Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors, or somatization?.Gut. 2008; 57: 1666-1673Crossref PubMed Scopus (84) Google Scholar and impaired quality of life in FD.37Van Oudenhove L. Vandenberghe J. Vos R. et al.Abuse history, depression, and somatization are associated with gastric sensitivity and gastric emptying in functional dyspepsia.Psychosom Med. 2011; 73: 648-655Crossref PubMed Scopus (14) Google Scholar Further, somatization is associated with health care use and predicts a poor response to treatment, including increasing one's likelihood of discontinuing medication due to perceived adverse effects.38Agosti V. Quitkin F.M. Stewart J.W. et al.Somatization as a predictor of medication discontinuation due to adverse events.Int Clin Psychopharmacol. 2002; 17: 311-314Crossref PubMed Google Scholar Therefore, assessing somatization by checking severity of multiple somatic symptoms remains clinically useful. Somatization has been thought to explain the frequent extraintestinal symptoms of IBS, and the high co-occurrence between FGID and other FSS,39Whitehead W.E. Palsson O.S. Levy R.R. et al.Comorbidity in irritable bowel syndrome.Am J Gastroenterol. 2007; 102: 2767-2776Crossref PubMed Scopus (84) Google Scholar and is a term that is commonly used in the medical literature to refer to medically unexplained syndromes (in parallel with the psychiatric terminology outlined here). There is extensive overlap among FSS—two-thirds of FGID patients experience symptoms of other FSS, including interstitial cystitis, chronic pelvic pain, headaches, and fibromyalgia,40Lackner J.M. Ma C.X. Keefer L. et al.Type, rather than number, of mental and physical comorbidities increases the severity of symptoms in patients with irritable bowel syndrome.Clin Gastroenterol Hepatol. 2013; 11: 1147-1157Abstract Full Text Full Text PDF PubMed Google Scholar independent of psychiatric comorbidity, but the question whether the different FSS represent truly distinct disorders ("splitter" view) or different manifestations of a common underlying pathophysiological process ("lumper" view) remains unresolved at present and falls outside the scope of this article. Overlapping psychological constructs, including health anxiety (gastrointestinal) symptom-specific anxiety, attentional bias, symptom hypervigilance, and catastrophizing, have been linked to FGID independent of psychiatric comorbidity, and are important treatment targets for CBT (see Psychological Treatments section)41Chilcot J. Moss-Morris R. Changes in illness-related cognitions rather than distress mediate improvements in irritable bowel syndrome (IBS) symptoms and disability following a brief cognitive behavioural therapy intervention.Behav Res Ther. 2013; 51: 690-695Crossref PubMed Scopus (12) Google Scholar (Figure 3). An overview of these processes and their roles in FGID is provided in Table 1.Table 1Cognitive−Affective Processes Influencing the Symptom Experience in Functional Gastrointestinal DisordersTermDefinitionAssociation with FGIDOutcomesManagementIllness anxietyGlobal tendency to worry about current and future bodily symptoms, formerly referred to as hypochondriasisLow insightExtensive research into what is wrongNot easily reassured,Lack of acceptanceRisk factor for development of FGIDChronicitySocial dysfunction, occupational difficulties,High health costs,Negative doctor−patient relationship,Poor treatment responseResponsive to CBTSymptom-specific anxietyWorry/hypervigilance around the likelihood/presence of specific symptoms and the contexts in which they occurBelief that normal gut sensations are harmful or will lead to negative consequencesPromotes GI symptomsDrives health care useNegatively impacts treatment responseAerophagia improved with distractionMay be differentially responsive to interoceptive exposure-based behavior therapyHypervigilance/ attentional biasAltered attention toward, and increased engagement with, symptoms and reminder of symptomsIBS patients showed higher recall of pain words and GI words compared with healthy controlsNCCP patients hypervigilant toward cardiopulmonary sensationsDismiss signs of improvementIgnore information suggesting that their FGID is not seriousResponsive to CBTCatastrophizing2-pronged cognitive process in which an individual magnifies the seriousness of symptoms and consequences while simultaneously viewing themselves as helplessResults in symptom amplificationIncreased painInhibits pain inhibitionNegatively affects interpersonal relationshipsLeads to increased worry, suffering, disabilityHigh symptom reportingReduced quality of lifeCan impact patient self-reportBurdens providerImproves with CBTMediates outcomeNCCP, noncardiac chest pain. Open table in a new tab NCCP, noncardiac chest pain. Here we give an overview of the neurophysiological mechanisms that explain the link between psychological processes, psychiatric comorbidity, and FGID symptoms described in the previous sections. Specifically, the critical role of bidirectional signaling mechanisms between the GI tract and the central nervous system are discussed, including the central processes involved in modulation of visceral afferent signals and the influence of efferent output of central stress and emotional−arousal circuits on motor, barrier, and immune functions of the GI tract. Finally, the emerging evidence on bidirectional communication between the gut microbiota and the (emotional) brain is outlined briefly. The "brain−gut axis" is the bidirectional neurohumoral communication system between the brain and the gut that is continuously signaling homeostatic information about the physiological condition of the body to the brain through afferent neural (spinal and vagal) and humoral "gut−brain" pathways.42Mayer E.A. Tillisch K. The brain-gut axis in abdominal pain syndromes.Annu Rev Med. 2011; 62: 381-396Crossref PubMed Scopus (120) Google Scholar Under normal physiological conditions, most of these interoceptive gut−brain signals are not consciously perceived. However, the subjective experience of visceral pain results from the conscious perception of salient gut−brain signals induced by noxious stimuli, which indicate a potential threat to homeostasis, thereby requiring a behavioral response. In the brain, [visceral afferent] interoceptive signals are processed in a homeostatic−afferent network (brainstem sensory nuclei, thalamus, posterior insula) and integrated with and modulated by emotional−arousal (locus coeruleus, amygdala, subgenual anterior cingulate cortex) and cortical−modulatory (prefrontal cortex and anterior insula, perigenual anterior cingulate cortex) neurocircuits. Key regions in these emotional−arousal and cortical−modulatory circuits project in a "top-down" fashion to brainstem areas, such as the periaqueductal gray and the rostral ventrolateral medulla, which, in turn, send descending projections to the dorsal horn of the spinal cord, where pain transmission is modulated (descending modulatory system) (Figure 4). Thus, [visceral] pain perception does not display a linear relationship with the intensity of peripheral afferent input, but rather emerges from a complex psychobiological process whereby visceral afferent input is processed and continuously modulated by cognitive and affective circuits at the level of the brain and through descending modulatory pathways. These mechanisms help understand the influence of the cognitive and affective processes outlined in the previous section on GI symptom perception in FGID patients, as well as the therapeutic effect of interventions targeting these processes, and constitute the basis for a model of FGID as disorders of gut−brain signaling. More specifically, dysfunction of these modulatory systems might allow physiological (non-noxious) stimuli to be perceived as painful or unpleasant (visceral hypersensitivity), which can lead to chronic visceral pain and/or discomfort, hallmark symptoms of FGID. The results of functional brain imaging studies in FGID will be outlined and should be interpreted within this framework. The exact nature of the visceral hyperalgesia or hypersensitivity found in a substantial subset of IBS and FD patients remains unclear. The concept of "visceral hypersensitivity" is operationalized as lower pain thresholds during visceral sensory testing, that is, reporting pain at lower pressures or volumes during repeated ascending inflations of a GI balloon catheter. However, as we have outlined, it is becoming increasingly clear that psychological processes and psychosocial factors can influence visceral perceptual sensitivity. Several studies suggest that an increased psychological tendency to report pain, which can be driven by hypervigilance, underlies the decreased pain thresholds in IBS patients, rather than increased neurosensory sensitivity.43Dorn S.D. Palsson O.S. Thiwan S.I.M. et al.Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity.Gut. 2007; 56: 1202-1209Crossref PubMed Scopus (99) Google Scholar Studies on the effects of stressors on perception of colorectal distention in healthy subjects and IBS patients have produced somewhat inconsistent findings, due to variations among the stressors used or potential confounders, such as distraction. However, a study that controlled for distraction demonstrated that IBS patients, but not healthy subjects, rated rectal distension more intense and unpleasa
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