anxiety or survival instinct?

Hi Angry So true Just the though of not having a bathroom room when you have IBS-Dis enough to cause everyone even if they dont have IBS-D anxiety..Last night I was at the store and the cashier had allready rang the items upand I look in my purse and my wallet was gone...Total Panic..because we had justgot paid..so I ran to the car scared to death and it had fell out of my pocket book on the floor and I had left the doors unlocked ...It was there and I was happy....Anxiety is a part of everyones life no matter who ...and I dont believe it is a defect...like you said human nature and part of our body make-up...Just curious did you deletethe post you had on here the other day about anxiety ? It was there and then it was gone.IBS-D has ruled to many years of my life worrying about finding a bathroom and comingobsessed with it....I had every pit stop lined up here on the East Coast....Have a nice weekend

Hi Angry So true Just the though of not having a bathroom room when you have IBS-Dis enough to cause everyone even if they dont have IBS-D anxiety..Last night I was at the store and the cashier had allready rang the items upand I look in my purse and my wallet was gone...Total Panic..because we had justgot paid..so I ran to the car scared to death and it had fell out of my pocket book on the floor and I had left the doors unlocked ...It was there and I was happy....Anxiety is a part of everyones life no matter who ...and I dont believe it is a defect...like you said human nature and part of our body make-up...Just curious did you deletethe post you had on here the other day about anxiety ? It was there and then it was gone.IBS-D has ruled to many years of my life worrying about finding a bathroom and comingobsessed with it....I had every pit stop lined up here on the East Coast....Have a nice weekend

angry, I agree. I never could figure out why people & drs( ) think it is unusual or some sort of weakness for a person to have anxiety about not being able to control their bowels. From the time we are out of diapers it is drilled into our heads that we must use the toilet not our pants to relieve ourselves and that it is a major no-no to have an 'accident'. We call it an accident but at the same time add shame and disgrace to the 'accident'. Now I knew a few toddlers who would occasionaly go in their pants just to get attention but I find it hard to believe that most adults have accidents for that reason.Sooo.... wouldn't it make sense that if someone can not always control when they have to go and may indeed have an accident in a public place that this may cause anxiety? People may call this bowel obsessed but what if a person were to vomit every time they ate ? Would they be stomach obsessed. Aren't people who have seizures anxious about having the next one? It is human nature to be anxious about the things we can't control ,especially when it comes to our bodies. Now I think if the anxiety is really affecting ones life to the point where they can't function at all they do need some kind of help .But I think it is ridiculous for those who have IBS D or D for any other reason to be told it is unreasonable that we feel anxiety about it. Obviously those who deal that line of **** to others haven't been standing in line at the bathrooms at Disney World praying that someone will let you cut in line or you will fill your pants right there in front of everyone,including your own children,or on an airplane or in someone elses car,or their childs graduation.You name it. Call me crazy but having D ( or just the feeling that it is inevitable) in public will cause me to have anxiety every time.

angry, I agree. I never could figure out why people & drs( ) think it is unusual or some sort of weakness for a person to have anxiety about not being able to control their bowels. From the time we are out of diapers it is drilled into our heads that we must use the toilet not our pants to relieve ourselves and that it is a major no-no to have an 'accident'. We call it an accident but at the same time add shame and disgrace to the 'accident'. Now I knew a few toddlers who would occasionaly go in their pants just to get attention but I find it hard to believe that most adults have accidents for that reason.Sooo.... wouldn't it make sense that if someone can not always control when they have to go and may indeed have an accident in a public place that this may cause anxiety? People may call this bowel obsessed but what if a person were to vomit every time they ate ? Would they be stomach obsessed. Aren't people who have seizures anxious about having the next one? It is human nature to be anxious about the things we can't control ,especially when it comes to our bodies. Now I think if the anxiety is really affecting ones life to the point where they can't function at all they do need some kind of help .But I think it is ridiculous for those who have IBS D or D for any other reason to be told it is unreasonable that we feel anxiety about it. Obviously those who deal that line of **** to others haven't been standing in line at the bathrooms at Disney World praying that someone will let you cut in line or you will fill your pants right there in front of everyone,including your own children,or on an airplane or in someone elses car,or their childs graduation.You name it. Call me crazy but having D ( or just the feeling that it is inevitable) in public will cause me to have anxiety every time.

Angry, this is kind of related as it's about survival & anxiety. I don't know if this is scientifically/medically true.. but anyway, I believe it's what my problem is. After several years of being in 'flight or fight' mode from life events, the adrenalin/anxiety 'flight or fight' response switch has been switched on so many times in order to survive, that eventually it just stays on. We know what happens in a flight or fight response - our bodies get prepared for action. This includes emptying the bowels to make us lighter for greater speed in flight. Evolutionary throwback!

Angry, this is kind of related as it's about survival & anxiety. I don't know if this is scientifically/medically true.. but anyway, I believe it's what my problem is. After several years of being in 'flight or fight' mode from life events, the adrenalin/anxiety 'flight or fight' response switch has been switched on so many times in order to survive, that eventually it just stays on. We know what happens in a flight or fight response - our bodies get prepared for action. This includes emptying the bowels to make us lighter for greater speed in flight. Evolutionary throwback!

The anxiety is not always concious and the brain remembers every attack you have ever had.Brain-Gut Interaction in Irritable Bowel Syndrome: New Findingsof a Multicomponent Disease ModelMax J. Schmulson MDFunctional Bowel Disorders Clinic and Gastrointestinal Laboratory, Department of Gastroenterology, National Institute ofMedical Sciences and Nutrition Salvador Zubira� n, Panamerican University of Mexico, and Sistema Nacional deInvestigadores de Me� xico, Mexico City, MexicoKey words: irritable bowel syndrome, functional bowel disorders, pathophysiology, disease model, sensory perceptionabnormalitiesAbstractKnowledge on the pathophysiology of irritable bowel syndromehas evolved, beginning with disturbances in motility to visceralhypersensitivity, and ultimately to alterations in brain-gut bi-directional communication, where neurotransmitters such asserotonin play a key role. Recently, a multicomponent diseasemodel that integrates all these alterations was proposed. Thismodel is divided into physiological, cognitive, emotional andbehavioral components that explain the gastrointestinal as wellas the constitutional symptoms. In recent years there has beenan explosion of research together with new developments inpharmacological treatments for IBS that support each compo-nent of this model. This review presents recent data in favor ofthese alterations in IBS.IMAJ 2001;3:104-110Irritable bowel syndrome together with functional dyspepsiaand non-cardiac chest pain encompass the three most commonfunctional bowel disorders. Functional as opposed to organicsyndromes are defined as those presenting pain and/ordiscomfort unexplained by structural abnormalities detectablewith currently available diagnostic modalities [1]. In the absenceof a reliable biological marker, the diagnosis of IBS, as withother functional bowel disorders, is based on recently revisedsymptom criteria known as the Rome II criteria [2]. Theseemphazise a ``positive diagnosis,'' meaning the presence of thesymptoms rather than exhaustive tests to exclude other diseases.Although the accuracy and pathophysiologic significance haveyet to be reported, the Rome criteria constitute probably themost reasonable approach for clinical diagnosis and researchpurposes.Since the 1950s our knowledge has evolved in the attempt toexplain IBS � from alterations in bowel motility to visceralhyperalgesia, and from alterations in brain-gut interactions toneuroendocrine abnormalities where 5-hydroxytryptamine hasbeen the focus of recent attention as a mediator of gut motilityIBS = irritable bowel syndromeand visceral sensitivity. An emerging approach proposed byMayer [1] integrates all these concepts in a more comprehensivedisease model that includes physiological alterations within thecentral nervous system. These may manifest as alterations in thecentral processing or modulation of visceral information,altered autonomic input to the gut, and altered neuroendocrineresponse to stress. Additionally, cognitive factors such asinappropriate coping styles, illness behavior and inappropriateconcepts about disease may influence healthcare utilization andmay play a role in turning a subject with IBS symptoms frombeing a non-patient to a healthcare-seeking patient. Emotionalfactors such as anxiety and depression, and behavioral factorssuch as stressful or traumatic life events contribute to symptomgeneration and exacerbation. This model is able to explainsymptoms of pain or discomfort caused by enhanced visceralsensitivity, alterations in bowel habit by autonomic disregula-tion, and other constitutional symptoms such as alterations inappetite, libido, sleep and energy [1,3]. This review presentsrecent data supporting these alterations in IBS.Physiological factorsVisceral hypersensitivityIn 1973 Ritchie [4] was the first to provide evidence for theconcept of visceral hypersensitivity in IBS. Patients and controlswere evaluated for their pain thresholds in response toprogressive distension of a balloon placed in the sigmoid colon.At the same volume of distension, the patients reported higherpain scores compared to the controls. This finding has beenreproduced by further studies. With the introduction of thebarostat, a computerized distension device, the distensionprocedures have been standarized. Physiological studies indicatethe presence of visceral hypersensitivity as the most consistentabnormality in chronic abdominal pain syndromes such as IBS.Two concepts of visceral hypersensitivity have been intro-duced � hyperalgesia and allodynia. Normal visceral sensationsare experienced at lower intraluminal volumes suggestinghyperalgesia, and pain or discomfort is experienced at volumesusually producing normal internal sensations, a finding referredto as allodynia [5]. At least four mechanisms have been proposedto explain visceral hypersensitivity: a) increased end-organsensitivity, spinal hyperexcitability with activation of nitricMexico�Israel Symposium104 M.J. Schmulson IMA J. Vol 3 . February 2001

The anxiety is not always concious and the brain remembers every attack you have ever had.Brain-Gut Interaction in Irritable Bowel Syndrome: New Findingsof a Multicomponent Disease ModelMax J. Schmulson MDFunctional Bowel Disorders Clinic and Gastrointestinal Laboratory, Department of Gastroenterology, National Institute ofMedical Sciences and Nutrition Salvador Zubira� n, Panamerican University of Mexico, and Sistema Nacional deInvestigadores de Me� xico, Mexico City, MexicoKey words: irritable bowel syndrome, functional bowel disorders, pathophysiology, disease model, sensory perceptionabnormalitiesAbstractKnowledge on the pathophysiology of irritable bowel syndromehas evolved, beginning with disturbances in motility to visceralhypersensitivity, and ultimately to alterations in brain-gut bi-directional communication, where neurotransmitters such asserotonin play a key role. Recently, a multicomponent diseasemodel that integrates all these alterations was proposed. Thismodel is divided into physiological, cognitive, emotional andbehavioral components that explain the gastrointestinal as wellas the constitutional symptoms. In recent years there has beenan explosion of research together with new developments inpharmacological treatments for IBS that support each compo-nent of this model. This review presents recent data in favor ofthese alterations in IBS.IMAJ 2001;3:104-110Irritable bowel syndrome together with functional dyspepsiaand non-cardiac chest pain encompass the three most commonfunctional bowel disorders. Functional as opposed to organicsyndromes are defined as those presenting pain and/ordiscomfort unexplained by structural abnormalities detectablewith currently available diagnostic modalities [1]. In the absenceof a reliable biological marker, the diagnosis of IBS, as withother functional bowel disorders, is based on recently revisedsymptom criteria known as the Rome II criteria [2]. Theseemphazise a ``positive diagnosis,'' meaning the presence of thesymptoms rather than exhaustive tests to exclude other diseases.Although the accuracy and pathophysiologic significance haveyet to be reported, the Rome criteria constitute probably themost reasonable approach for clinical diagnosis and researchpurposes.Since the 1950s our knowledge has evolved in the attempt toexplain IBS � from alterations in bowel motility to visceralhyperalgesia, and from alterations in brain-gut interactions toneuroendocrine abnormalities where 5-hydroxytryptamine hasbeen the focus of recent attention as a mediator of gut motilityIBS = irritable bowel syndromeand visceral sensitivity. An emerging approach proposed byMayer [1] integrates all these concepts in a more comprehensivedisease model that includes physiological alterations within thecentral nervous system. These may manifest as alterations in thecentral processing or modulation of visceral information,altered autonomic input to the gut, and altered neuroendocrineresponse to stress. Additionally, cognitive factors such asinappropriate coping styles, illness behavior and inappropriateconcepts about disease may influence healthcare utilization andmay play a role in turning a subject with IBS symptoms frombeing a non-patient to a healthcare-seeking patient. Emotionalfactors such as anxiety and depression, and behavioral factorssuch as stressful or traumatic life events contribute to symptomgeneration and exacerbation. This model is able to explainsymptoms of pain or discomfort caused by enhanced visceralsensitivity, alterations in bowel habit by autonomic disregula-tion, and other constitutional symptoms such as alterations inappetite, libido, sleep and energy [1,3]. This review presentsrecent data supporting these alterations in IBS.Physiological factorsVisceral hypersensitivityIn 1973 Ritchie [4] was the first to provide evidence for theconcept of visceral hypersensitivity in IBS. Patients and controlswere evaluated for their pain thresholds in response toprogressive distension of a balloon placed in the sigmoid colon.At the same volume of distension, the patients reported higherpain scores compared to the controls. This finding has beenreproduced by further studies. With the introduction of thebarostat, a computerized distension device, the distensionprocedures have been standarized. Physiological studies indicatethe presence of visceral hypersensitivity as the most consistentabnormality in chronic abdominal pain syndromes such as IBS.Two concepts of visceral hypersensitivity have been intro-duced � hyperalgesia and allodynia. Normal visceral sensationsare experienced at lower intraluminal volumes suggestinghyperalgesia, and pain or discomfort is experienced at volumesusually producing normal internal sensations, a finding referredto as allodynia [5]. At least four mechanisms have been proposedto explain visceral hypersensitivity: a) increased end-organsensitivity, spinal hyperexcitability with activation of nitricMexico�Israel Symposium104 M.J. Schmulson IMA J. Vol 3 . February 2001

oxide and other neurotransmitters, c) long-term hyperalgesiadue to the development of neuroplasticity in response to chronicvisceral stimulation, and d) alterations in endogenous modula-tion at cortical and brainsteam levels of the nociception [5].Aside from hypersensitivity, at least a second perceptualalteration can be distinguished � hypervigilance. It refers to agreater propensity to label negatively expected aversive sensa-tions [6]. Hypervigilance may explain other extraintestinalsymptoms in IBS and the co-occurrence of other syndromessuch as fibromyalgia, and may determine whether predominantsymptom expression involves the muskuloskeletal system,gastrointestinal system or both. Fibromyalgia occurs in up to65% of patients with IBS, and functional bowel symptomsoccur in 65�70% of patients with fibromyalgia [7].. Pain pathways. To understand these perceptual alterations weshould state that there is a continual bi-directional communica-tion between brain and gut. Bowel pain inputs are transmittedthrough three orders of neurons. The first carries informationfrom the viscera through the thoracolumbar sympatheticnervous system and synapses in the dorsal horn of the spinalcord. Neuropeptides or excitatory amino acids released fromprimary afferents interact with receptors such as substance Pand calcitonin gene-related peptides, and Ca enters through N-Methyl-D-Aspartate receptors resulting in nitric oxide synthe-tase. Nitric oxide is then released and diffuses to the presynapticterminal, producing a positive feedback and hypersensitivity byfacilitating neurotransmitter release [8]. The second order thencrosses the midline of the spinal cord and ascends via thespinothalamic tract to synapse with the thalamus, and via thespinoreticular tract to synapse with the reticular formation. Thethird ascends from the spinothalamic system to the somatosen-sory cortex and from the spinoreticular tract to the limbicsystem (including the anterior cingulate) and prefrontal cortices.The first order provides the sensory-discriminative component,whereas the second provides the motivational-affective andevaluative component [8].One of several endogenous neural systems that modulateperipheral sensory input is the descending endorphin-mediatedanalgesia. It descends from the cortex and hypothalamus to theperi-aqueductal gray area in the midbrain, then traverses andsynapses in the nucleus raphe magnus in the medulla, ending atthe dorsal horn of the spinal cord where it increases or decreasesthe afferent information arising from the first order neurons.This system may be facilitated by mediators such as serotonin(5-HT1) and norepinephrine [8].Viscerosomatic perception abnormalities. Altered rectal-sigmoid perception. Altered rectal perception hasbeen proposed as a biological marker of IBS. It is found in theform of lowered thresholds for aversive sensations, increasedintensity of sensations, or altered viscerosomatic referral [9].Using the barostat, hypersensitivity was found only for aversive5-HT = 5-hydroxytryptaminesensations in response to rapid phasic distension but not to slowramp distension [9]. Two subgroups of patients with predomi-nant IBS constipation have been identified on the basis ofresponses to different types of rectal distension: those who havelost the natural call to stool (no urge), and those who experiencea constant sensation of incomplete evacuation (urge) [10]. Bothgroups were hypersensitive to an ascending series of phasicrectal distensions distinguishing patients from controls.Furthermore, the no-urge group was hyposensitive to a slowgradual distension of the rectum. The first finding is consistentwith hypervigilance towards aversive visceral stimulationelicited by predictable increasing phasic distensions of therectum [6]. The second finding may result from an increase incentral pain-inhibitory mechanisms, or alternatively from afailure to activate central attentional systems in response tophysiological rectal filling [10]. Using a double-balloon catheterand barostat-driven distensions in the rectum and sigmoidcolon, Munakata and co-workers [11] reported that afterrepetitive rapid phasic distensions (30 seconds, 60 mmHg) inthe sigmoid colon, there was a significant reduction in rectalperception thresholds in IBS patients but not in controlsubjects. A failure in central pain-modulating systems wassuggested as the pathophysiological basis.Finally, the perceptual responses to visceral aversive stimuliin IBS are altered with the co-existence of fibromyalgia. Rectalperception thresholds are significantly lower in patients withIBS than in nomals subjects and those with both IBS+fibro-myalgia, whereas after sigmoid conditioning patients withIBS+fibromyalgia developed rectal hypersensitivity similar toIBS alone [12].. Somatic hypoalgesia. Hypersensitivity is specific to the bowel,since IBS patients have somatic hypoalgesia [7]. This hypoalge-sia seems to be specific to mechanical but not thermal pain,while hypervigilance to thermal but not somatic pain has beenreported in IBS, suggesting that the processing of thermal andmechanical pain is differentially modulated in IBS [13].Conversely, patients with both IBS+fibromyalgia have somatichyperalgesia [7]. Modality-specific alterations in descendingpain-modulation systems may explain the distinct somatic andvisceral perceptual responses in IBS patients.Viscerosensory symptomsAbdominal pain is thought to be the hallmark of IBS, althoughin the currently revised Rome II diagnostic criteria [2]``discomfort'' was added to ``pain'' to broaden symptomdescription. In a recent study in a tertiary referral populationof IBS patients, only a third of the patients reported that theirmost bothersome viscerosensory symptom was abdominal pain,from the four group cluster of abdominal pain, bloating-typediscomfort, sensation of incomplete evacuation, and extra-abdominal (chest pain or pressure and nausea). Yet, althoughpain predominance did not correlate with the severity ofgastrointestinal or psychological symptoms, there was asignificant correlation with the development of rectal hyper-Mexico�Israel Symposium105 IMA J. Vol 3 . February 2001 Brain-Gut Interaction in Irritable Bowel Syndrome

oxide and other neurotransmitters, c) long-term hyperalgesiadue to the development of neuroplasticity in response to chronicvisceral stimulation, and d) alterations in endogenous modula-tion at cortical and brainsteam levels of the nociception [5].Aside from hypersensitivity, at least a second perceptualalteration can be distinguished � hypervigilance. It refers to agreater propensity to label negatively expected aversive sensa-tions [6]. Hypervigilance may explain other extraintestinalsymptoms in IBS and the co-occurrence of other syndromessuch as fibromyalgia, and may determine whether predominantsymptom expression involves the muskuloskeletal system,gastrointestinal system or both. Fibromyalgia occurs in up to65% of patients with IBS, and functional bowel symptomsoccur in 65�70% of patients with fibromyalgia [7].. Pain pathways. To understand these perceptual alterations weshould state that there is a continual bi-directional communica-tion between brain and gut. Bowel pain inputs are transmittedthrough three orders of neurons. The first carries informationfrom the viscera through the thoracolumbar sympatheticnervous system and synapses in the dorsal horn of the spinalcord. Neuropeptides or excitatory amino acids released fromprimary afferents interact with receptors such as substance Pand calcitonin gene-related peptides, and Ca enters through N-Methyl-D-Aspartate receptors resulting in nitric oxide synthe-tase. Nitric oxide is then released and diffuses to the presynapticterminal, producing a positive feedback and hypersensitivity byfacilitating neurotransmitter release [8]. The second order thencrosses the midline of the spinal cord and ascends via thespinothalamic tract to synapse with the thalamus, and via thespinoreticular tract to synapse with the reticular formation. Thethird ascends from the spinothalamic system to the somatosen-sory cortex and from the spinoreticular tract to the limbicsystem (including the anterior cingulate) and prefrontal cortices.The first order provides the sensory-discriminative component,whereas the second provides the motivational-affective andevaluative component [8].One of several endogenous neural systems that modulateperipheral sensory input is the descending endorphin-mediatedanalgesia. It descends from the cortex and hypothalamus to theperi-aqueductal gray area in the midbrain, then traverses andsynapses in the nucleus raphe magnus in the medulla, ending atthe dorsal horn of the spinal cord where it increases or decreasesthe afferent information arising from the first order neurons.This system may be facilitated by mediators such as serotonin(5-HT1) and norepinephrine [8].Viscerosomatic perception abnormalities. Altered rectal-sigmoid perception. Altered rectal perception hasbeen proposed as a biological marker of IBS. It is found in theform of lowered thresholds for aversive sensations, increasedintensity of sensations, or altered viscerosomatic referral [9].Using the barostat, hypersensitivity was found only for aversive5-HT = 5-hydroxytryptaminesensations in response to rapid phasic distension but not to slowramp distension [9]. Two subgroups of patients with predomi-nant IBS constipation have been identified on the basis ofresponses to different types of rectal distension: those who havelost the natural call to stool (no urge), and those who experiencea constant sensation of incomplete evacuation (urge) [10]. Bothgroups were hypersensitive to an ascending series of phasicrectal distensions distinguishing patients from controls.Furthermore, the no-urge group was hyposensitive to a slowgradual distension of the rectum. The first finding is consistentwith hypervigilance towards aversive visceral stimulationelicited by predictable increasing phasic distensions of therectum [6]. The second finding may result from an increase incentral pain-inhibitory mechanisms, or alternatively from afailure to activate central attentional systems in response tophysiological rectal filling [10]. Using a double-balloon catheterand barostat-driven distensions in the rectum and sigmoidcolon, Munakata and co-workers [11] reported that afterrepetitive rapid phasic distensions (30 seconds, 60 mmHg) inthe sigmoid colon, there was a significant reduction in rectalperception thresholds in IBS patients but not in controlsubjects. A failure in central pain-modulating systems wassuggested as the pathophysiological basis.Finally, the perceptual responses to visceral aversive stimuliin IBS are altered with the co-existence of fibromyalgia. Rectalperception thresholds are significantly lower in patients withIBS than in nomals subjects and those with both IBS+fibro-myalgia, whereas after sigmoid conditioning patients withIBS+fibromyalgia developed rectal hypersensitivity similar toIBS alone [12].. Somatic hypoalgesia. Hypersensitivity is specific to the bowel,since IBS patients have somatic hypoalgesia [7]. This hypoalge-sia seems to be specific to mechanical but not thermal pain,while hypervigilance to thermal but not somatic pain has beenreported in IBS, suggesting that the processing of thermal andmechanical pain is differentially modulated in IBS [13].Conversely, patients with both IBS+fibromyalgia have somatichyperalgesia [7]. Modality-specific alterations in descendingpain-modulation systems may explain the distinct somatic andvisceral perceptual responses in IBS patients.Viscerosensory symptomsAbdominal pain is thought to be the hallmark of IBS, althoughin the currently revised Rome II diagnostic criteria [2]``discomfort'' was added to ``pain'' to broaden symptomdescription. In a recent study in a tertiary referral populationof IBS patients, only a third of the patients reported that theirmost bothersome viscerosensory symptom was abdominal pain,from the four group cluster of abdominal pain, bloating-typediscomfort, sensation of incomplete evacuation, and extra-abdominal (chest pain or pressure and nausea). Yet, althoughpain predominance did not correlate with the severity ofgastrointestinal or psychological symptoms, there was asignificant correlation with the development of rectal hyper-Mexico�Israel Symposium105 IMA J. Vol 3 . February 2001 Brain-Gut Interaction in Irritable Bowel Syndrome

ingly, altered autonomic outflow presents as alterations inbowel habits, altered perceptual responses manifest as viscero-and somatosensory symptoms, and constitutional functions.We recently reported that patients with ``hard/lumpy'' stools,a criterion for constipation, had lower rectal thresholds tomechanical distension than those with normal stools; likewise,patients with the diarrhea-supporting criterion ``loose/watery''stools had higher thresholds than those with normal stools [15].We also found that in IBS patients without fibromyalgia, thosein the IBS-C group, as compared to the IBS-D group, showed agreater prevalence of a wide range of symptoms related to theupper and lower abdomen and to musculoskeletal andconstitutional functions such as early satiety, fullness, upperabdominal bloating, higher severity ratings for lower gastro-intestinal bloating, neck/shoulders and back/hip pain, sleepimpairment, loss of appetite and decreased sexual function [27].Effect of foodMost patients with IBS report that food excacerbates theirsymptoms. Food intake could result in symptoms via excessiveactivation of mechanoreceptors due to increased intraluminalvolumes or increased motor activity, such as a prolongedgastrocolonic response, increased gas production resulting inintestinal distension, interaction of food components withchemoreceptors in the mucosa, and triggering of true allergicresponses [5]. We have shown that gastrocolonic response inIBS patients induced an increase in rectal tone and a reductionin rectal compliance in IBS-D patients as well as a decrease inrectal perception threshold in this subgroup [28]. These findingscould explain the postprandial urgency reported by IBS-Dpatients. Furthermore, a variety of food components, includingglucose, amino acids and fatty acids, interact via the release ofchemical substances such as cholecystokinin. Cholecystokinin-mediated activation of vagal chemoreceptors plays a role in theregulation of gastric and intestinal motility, and activation ofmechanoreceptive vagal afferents may play a role in modulationof visceral perception [5].Capsaicin, the pungent ingredient of peppers, has been wellcharacterized as a selective stimulant of unmyelinated C-fibersensory afferent neurons, such as the peripheral terminals ofspinal and vagal afferents. Approximately 80% of C-fiberafferent neurons are polymodal ``silent'' nociceptors activatedby noxious thermal, mechanical or chemical stimuli. Capsaicinstimulation results in many physiological effects such as bloodflow alteration, smooth muscle contractility, and the release ofmany neuropeptides including substance P, known to mediatepain [5]. We have shown that 1 g of guajillo chili pepper(0.112% of capsaicin) with each meal for 7 days in patients withIBS significantly decreased the rectal pain threshold to anascending series of mechanical distensions (tolerance threshold)[29]. It appears that the development of mechanosensitivity of apopulation of ``silent'' C fibers in response to chemical irritantsis related to changes in the signal transduction mechanism ofperipheral nerve terminals [5].Gender differencesWomen are more likely than men to report IBS symptoms. Inthe U.S. Householder Survey [30], IBS was present in 14.5% ofwomen but in only 7.7% of men. Similarly, in Mexico, in asmall study on subjects aged 17�22 years, IBS was present in29.7% of women and 6.6% of men [31]. Within clinicalpopulations the proportion of women seen ranges from 75 to80%; however, these differences are reversed in India [30,32],which is probably due to differences in access to medical care.Female patients report higher levels of a variety of intestinal andnon-intestinal sensory symptoms despite similar levels of IBSseverity, abdominal pain, psychological symptoms and illnessimpact [33]. In up to 40%, worsening of symptoms is seenduring the menstrual cycle [33], although no differences inplasma estradiol and progesterone levels between women withand without IBS symptoms have been demonstrated. Whilevariations related to menstrual cycle have been shown, thereseems to be no differences in relation to postmenopausal stage.Lower pain thresholds have been reported in female patients, aswell as in animals. Also, gender differences in the centralresponse to visceral pain and anticipation of pain evaluated withbrain PET have been reported in IBS. In contrast to females,male patients during rectal stimulation showed activation of theinsula, a brain region involved in autonomic control andantinociception. Moreover, compared with female patients,male IBS patients appear to have increased sympathetic outflowto heart and skin, differences that were not observed in controlsubjects. Finally, gender differences in therapeutic responses to5-HT3 receptor antagonists are consistent with differences inthe modulation of pain-processing networks by serotoninergicmechanisms [34].Cognitive factorsInappropriate coping styles, illness behavior and inappropriateconcepts about disease, nutrition and medications are commonin IBS patients. These factors may determine the response andability to cope with stressors and may influence healthcareutilization and clinical outcomes.It is generally assumed that patients seen in primary caresettings have less severe symptoms and less psychologicalcompromise than those seen in tertiary referral centers [30].Recruitment by advertisement is extensively used in clinicaltrials. Similarily, the characteristics of IBS patients respondingto such advertisements may differ from those attending aspecialty clinic. In a prospective study surveying 657 IBSpatients � 52% recruited from a functional bowel disordersclinic and 48% from advertisement for clinic trials � the clinicpopulation reported more prevalent and severe abdominal pain,higher psychological symptom scores, higher number of medicalvisits, and lower quality of life [35]. However, when visceralperception studies were conducted, both groups demonstratedevidence of hypersensitivity to rectal distension before and aftersigmoid stimulation, and there were no differences based onrecruitment source [35]. From these results it can be concluded107 IMA J. Vol 3 . February 2001 Brain-Gut Interaction in Irritable Bowel SyndromeMexico�Israel Symposium