Leah FitzGerald

Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia

Abstract Background: Irritable bowel syndrome (IBS) and fibromyalgia (FM) are considered chronic syndromes of altered visceral and somatic perception, respectively. Because there is a significant overlap of IBS and FM, shared pathophysiological mechanisms have been suggested. Although visceral perception has been well studied in IBS, somatic perception has not. Aims: To compare hypervigilance and altered sensory perception in response to somatic stimuli in patients with IBS, IBS+FM, and healthy controls. Methods: Eleven IBS females (mean age 40), 11 IBS+FM females (mean age 46), and ten healthy female controls (mean age 39) rated pain perception in response to pressure stimuli administered to active somatic tender points, non‐tender control points and the T‐12 dermatome, delivered in a predictable ascending series, and delivered in an unpredictable randomized fashion (fixed stimulus). Results: Although IBS patients had similar pain thresholds during the ascending series compared with controls, they were found to have somatic hypoalgesia with higher pain thresholds and lower pain frequency and severity during fixed stimulus series compared with IBS+FM patients and controls (P<0.05). Patients with IBS+FM were more bothered by the somatic stimuli and had somatic hyperalgesia with lower pain thresholds and higher pain frequency and severity. Conclusions: Both hypervigilance and somatic hypoalgesia contribute to the altered somatic perception in IBS patients. Co‐morbidity with FM results in somatic hyperalgesia in IBS patients.

Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia

OBJECTIVE:Symptoms of irritable bowel syndrome (IBS) and fibromyalgia (FM) commonly coexist. We hypothesized that one of the mechanisms underlying this comorbidity is increased activation of brain regions concerned with the processing and modulation of visceral and somatic afferent information, in particular subregions of the anterior cingulate cortex (ACC).METHODS:Regional cerebral blood flow (rCBF) was assessed in age-matched female IBS (n = 10) and IBS + FM (n = 10) subjects using H215O positron emission tomography during noxious visceral (rectal) and somatic pressure stimuli.RESULTS:GI symptom severity was significantly higher in the IBS patients compared with the IBS + FM patients (p < 0.05). In addition, IBS + FM patients rated somatic pain as more intense than their abdominal pain (p < 0.05). Whereas the somatic stimulus was less unpleasant than the visceral stimulus for IBS patients without FM, the somatic and visceral stimuli were equally unpleasant in the IBS + FM group. Group differences in regional brain activation were entirely within the middle subregion of the ACC. There was a greater rCBF increase in response to noxious visceral stimuli in IBS patients and to somatic stimuli in IBS + FM patients.CONCLUSION:Chronic stimulus-specific enhancement of ACC responses to sensory stimuli in both syndromes may be associated with cognitive enhancement of either visceral (IBS) or somatic (IBS + FM) sensory input and may play a key pathophysiologic role in these chronic pain syndromes.

The effect of life stress on symptoms of heartburn.

Objective: Psychosocial stressors have been associated with exacerbations of symptoms in functional and inflammatory disorders of the gastrointestinal tract. The present longitudinal study tests the general hypothesis that life stressors can exacerbate symptoms in patients with chronic heartburn. Methods: Sixty subjects with current heartburn symptoms were recruited by community advertisement and assessed for presence of stressful life events retrospectively over the preceding 6 months and prospectively for 4 months. Symptom severity by daily diary, quality of life, and psychological symptoms of anxiety, depression, and vital exhaustion were also measured. Results: The presence of a severe, sustained life stress during the previous 6 months significantly predicted increased heartburn symptoms during the following 4 months. In addition, symptoms showed a strong, independent correlation with vital exhaustion. Affective and subjective stress ratings were not strongly related to heartburn severity; however, anxiety showed the strongest relationship to impaired quality of life and depression to heartburn medication use. Conclusions: As with other chronic conditions such as irritable bowel syndrome (IBS), heartburn severity appears to be most responsive to major life events and not an accumulation of more minor stressors or fluctuations in mood. In addition, vital exhaustion, which may in part result from sustained stress, may represent the psychophysiological symptom complex most closely associated with heartburn exacerbation. Potential mechanisms for these results include increased level and frequency of esophageal acid exposure, inhibition of gastric emptying of acid, or stress-induced hypersensitivity.

Enhanced preattentive central nervous system reactivity in irritable bowel syndrome

OBJECTIVE:Irritable bowel syndrome (IBS) is a common functional disorder characterized by enhanced perceptual sensitivity and hypervigilance toward afferent signals from the viscera. We hypothesize that the increased responsiveness of IBS patients is a generalized phenomenon applying to stimuli other than visceral and attempt to demonstrate increased responsiveness to sounds as measured by the P1 scalp potential.METHODS:Event-related potentials were recorded from IBS patients and control subjects in an auditory task requiring detection of rare pitch targets in a designated ear. Visual words served as targets in an additional block.RESULTS:Compared to control subjects, IBS patients displayed a robust increase in the amplitude of the P1 scalp potential elicited by both attended and unattended sounds.RESULTS:Enhanced P1 indicates preattentive central nervous system dishabituation in response to repeated sounds. A generalized preattentive increase in central nervous system reactivity may be a feature that IBS shares with several anxiety disorders that frequently co-occur in these patients.

Audio and visual stimulation reduces patient discomfort during screening flexible sigmoidoscopy

Objective:Despite current recommendations calling for regular screening flexible sigmoidoscopies over the age of 50, only a small percentage of the population have regular examinations. Improving patient tolerance of flexible sigmoidoscopies could therefore increase patient compliance with these recommended guidelines. The aim of this study was to determine whether audio and visual stimulation reduces discomfort during flexible sigmoidoscopy and whether the effects of the stimulation are secondary to distraction.Methods:A total of 37 patients undergoing routine screening flexible sigmoidoscopy were randomized to receive no intervention, audio stimulation alone, or audio and visual stimulation. Patient discomfort ratings and affect states were measured prior to and immediately following flexible sigmoidoscopy using a visual analogue scale and the Stress Symptom Ratings (SSR) ratings.Results:Patients receiving audio and visual intervention had lower abdominal discomfort ratings (7.1 ± 1.4) than patients receiving audio stimulation (9.5 ± 1.3) or no intervention (10.8 ± 1.6) (p < 0.05). Patients receiving audio and visual intervention also had higher arousal (7.3 ± 0.4) and attention (9.2 ± 0.2) ratings than patients receiving no intervention (6.1 ± 0.4 and 6.2 ± 0.7, respectively) (p < 0.05). Anxiety and anger ratings, on the other hand, were significantly lower in patients receiving audio and visual intervention (2.5 ± 0.4, 1.4 ± 0.3, respectively) than patients receiving no intervention (4.4 ± 0.6, 3.6 ± 0.7).Conclusion:Audio and visual stimulation reduces abdominal discomfort associated with flexible sigmoidoscopy. This effect appears to be due to distraction.

Rumination in the laboratory: What happens when you go back to everyday life?

Rumination has been suggested to mediate the physiological consequences of stress on health. We studied the effects of rumination evoked in the laboratory and subsequent changes over 24 h. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were monitored in 27 male and 33 female participants during baseline, reading, an anger recall interview, and recovery. Half of the sample was assigned to a distraction condition. The lab session was followed by a 24-hour ambulatory (A)HR and BP recording and self-reports of moods and rumination. Rumination was associated with higher SBP, DBP, and HR and increased negative mood compared to distraction. Rumination during the day was a strong predictor of AHR, ABP, and mood. BP reactivity in the laboratory and increases in ABP during rumination were related. The effects of negative cognition on health go far beyond the recovery periods usually measured in the laboratory, thus playing a pathogenic role.

Evidence for alterations in central noradrenergic signaling in irritable bowel syndrome

BACKGROUND/AIMS Alterations in noradrenergic (NE) signaling have been implicated in the pathophysiology of irritable bowel syndrome (IBS), and adrenergic receptors are potential treatment targets. METHODS To characterize central NE signaling in IBS, 11 patients and 11 healthy controls (HCs) were studied 3 times during an auditory oddball vigilance task after double-blind ingestion of the α2-adrenoreceptor (α2AR) antagonist yohimbine (YOH), the α2AR agonist clonidine (CLO), or placebo (PLA). Regional cerebral glucose metabolism was measured with [¹⁸F] fluorodeoxyglucose (FDG) positron emission tomography (PET). Measures of anxiety, early-life trauma, plasma NE and blood pressure were acquired. RESULTS Patients had higher plasma NE levels than HCs before and after ingestion of all drugs (all p<0.05). YOH increased plasma NE and more anxiety in patients than in HCs. After YOH, NE levels directly correlated with drug-induced increases in anxiety in IBS patients (r=0.61), but not in HCs. IBS patients showed less YOH-mediated reduction of activity in a central arousal circuit, consistent with fewer functional presynaptic α2AR. In HCs, but not in patients, activation of amygdala and subgenual anterior cingulate cortex (sgACC) was inversely correlated with activation of anterior mid cingulate cortex (aMCC), and state anxiety covaried directly with activity in limbic and right frontotemporal cortices, but indirectly with activity in the left frontotemporal cortex. YOH-mediated reduction of activity in brainstem and amygdala inversely correlated with early life trauma. CONCLUSIONS IBS patients showed evidence for increased noradrenergic activity consistent with downregulation of presynaptic inhibitory α2ARs. Activity within central arousal circuits was biased toward greater excitability and reduced corticolimbic inhibition in IBS. Early life trauma may be one mediator of these abnormalities.

Walnuts Improve Semen Quality in Men Consuming a Western-Style Diet: Randomized Control Dietary Intervention Trial

ABSTRACT We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21–35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, −0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.

Is there a difference between abdominal pain and discomfort in moderate to severe IBS patients

OBJECTIVES:The aims of this study were to: 1) determine the relative prevalence of self-reported pain-predominant and discomfort-predominant symptom patterns in irritable bowel syndrome (IBS) patients; and 2) test the hypotheses that pain-predominant patients report higher GI symptom severity, show higher psychological symptom severity, show worse quality of life, and demonstrate higher health care use.METHODS:A total of 256 consecutive ROME I-positive IBS patients with moderate to severe symptoms were classified according to whether they rated their predominant IBS symptoms as pain (n = 52), or as nonpainful discomfort (n = 128) on the Irritable Bowel Syndrome Quality of Life questionnaire. The validity of this classification scheme was confirmed by interview in a subsample of 45 patients. IBS-specific symptom patterns, psychometric assessment, and health-related quality of life measures were obtained using validated survey instruments.RESULTS:Contrary to the generally accepted notion that pain is the most predominant symptom in IBS, twice as many patients self-classified their symptoms as abdominal discomfort rather than abdominal pain. The classifications based on questionnaire data were shown to be valid in a subsample of subjects (n = 45) who underwent classification based on an independent, blinded, clinical interview (r = 0.77, p < 0.05). Pain and discomfort subgroups were similar in age, gender, predominant bowel habit, and overall GI symptom severity. In addition, the subgroups reported similar degrees of psychological distress, impaired quality of life, and increased patterns of health care use.CONCLUSIONS:Subgroups of moderate to severe IBS patients do report their predominant GI symptoms in terms of pain or nonpainful discomfort, regardless of severity of their overall GI symptoms or psychological symptoms. These findings are most consistent with a cognitive labeling bias of visceral sensations as either pain or discomfort.

A randomized controlled study examining the effect of exercise on inflammatory cytokine levels in post-menopausal women

Background Elevated plasma levels of inflammatory cytokine are associated with body mass index, percent body fat and increased morbidity. Evidence suggests that higher levels of physical activity result in beneficial anti-inflammatory effects compared to a more sedentary lifestyle. Further, reproductive hormones are associated with inflammaotry cytokines. This study examined the effect of a 16-week low-moderate intensity exercise (EX) programme on reproductive hormones and inflammatory cytokines. Methods Twenty-eight healthy, sedentary post-menopausal women were randomly assigned to EX (n = 14) or control (Con, n = 14) groups. The EX group completed low-moderate intensity treadmill training 25–30 min/day, up to 55% of HRmax, 3–4 days/week, for 16-weeks. Con maintained current physical activity level. Baseline and week-16 serum samples evaluated interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, estradiol, luteinizing hormone and follicular stimulating hormone. Results Post-intervention, the EX group showed a significant decrease in interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, estradiol, follicular stimulating hormone and luteinizing hormone levels compared to baseline values. No significant changes were observed in Con. Significant correlations were observed between IL-1β, IL-6, TNF-α, and reproductive hormones, both before and after the exercise intervention. Conclusion Findings suggest that a low-moderate intensity EX programme decreases cytokines in relation to reproductive hormones in post-menopausal women. These findings support the role of EX in reducing inflammatory markers and improved reproductive hormones in post-menopausal women.