oxytocin and Irritable-Bowel-Syndrome

This article explicates a theory that oxytocin, a sexually dimorphic neurotransmitter and paracrine hormone, is a plausible mechanism linking early relational trauma with posttraumatic self disorders (e.g., dissociation, somatization, and interpersonal sensitivity), posttraumatic stress disorder, and pelvic visceral dysregulation disorders (e.g., irritable bowel syndrome, chronic pelvic pain, interstitial cystitis, and hyperemesis gravidarum). This posttraumatic oxytocin dysregulation disorders theory is consistent with the historical and contemporary literature. It integrates attention to psychological and physical comorbidities and could account for the increased incidence of these disorders among females. Specific propositions are explored in data from studies of traumatic stress and women's health.

Topics: Cystitis, Interstitial; Dissociative Disorders; Female; Humans; Hyperemesis Gravidarum; Interpersonal Relations; Irritable Bowel Syndrome; Models, Psychological; Models, Theoretical; Oxytocin; Pelvic Pain; Pregnancy; Pregnancy Complications; Psychophysiologic Disorders; Somatoform Disorders; Stress Disorders, Post-Traumatic

Irritable bowel syndrome (IBS) is characterized by gastrointestinal dysmotility and visceral hyperalgesia, and the impaired brain-gut axis is accepted as a crucial cause for the onset of IBS. The objective of this study is to investigate the effects of the adaptive changes in the central neural system induced by stress on IBS-like syndromes in rats. Long-term water avoidance stress (WAS) was used to prepare IBS animals. The changes in neuronal excitation and GABA expression were shown by immunohistochemistry. The mRNA and protein expressions of neurotransmitters were detected with Quantitative reverse-transcription PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The intestinal transit time, fecal moisture content, and abdominal withdrawal reflex scores of rats were recorded to monitor intestinal motility and visceral hyperalgesia. In the WAS-treated rats with enhanced intestinal motility and visceral hypersensitivity, more GABAergic projections were found in the paraventricular nucleus (PVN) of the hypothalamus, which inhibited the firing rate of neurons and decreased the expression of oxytocin. Exogenous oxytocin improved gut motility and decreased AWR scores. The inhibition of oxytocin by the adaptive GABAergic projection in the PVN might be an important mediator of IBS, which indicates a potential novel therapeutic target.

Topics: Animals; Feces; Hyperalgesia; Irritable Bowel Syndrome; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats

Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic-pituitary-adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown.. We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress.. Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment.. TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress.. It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.

Topics: Animals; Chronic Disease; Colon; Corticotropin-Releasing Hormone; Disease Models, Animal; Feedback, Physiological; Gastrointestinal Motility; Hypothalamo-Hypophyseal System; Irritable Bowel Syndrome; Male; Oxytocin; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley; Stress, Psychological; Transcutaneous Electric Nerve Stimulation; Treatment Outcome

Oxytocin and the oxytocin receptor have been demonstrated in the gastrointestinal (GI) tract and have been shown to exert physiological effects on gut motility. The role for oxytocin in the pathophysiology of GI complaints is unknown. The aim of this study was to examine genetic variations or polymorphism of oxytocin (OXT) and its receptor (OXTR) genes in patients with GI complaints without visible organic abnormalities.. Genetic variants in the OXT promoter region, and in the OXTR gene in DNA samples from 131 rigorously evaluated patients with Irritable Bowel Syndrome (IBS), 408 homozygous subjects referred for lactase (LCT-13910 C>T, rs4988235) genotyping, and 299 asymptomatic blood donors were compared. One polymorphism related to the OXT gene (rs6133010 A>G) and 4 related to the OXTR gene (rs1465386 G>T, rs3806675 G>A, rs968389 A>G, rs1042778 G>T) were selected for genotyping using Applied Biosystems 7900 HT allele discrimination assays.. There were no statistically significant differences in the genotype or allele frequencies in any of the SNPs when IBS patients were compared to healthy controls. Among subjects referred for lactase genotyping, the rs6133010 A>G OXT promoter A/G genotype tended to be more common in the 154 non-persistent (27.3%) subjects than in the 254 lactase persistant (18.1%) subjects and in the healthy controls (19.4%) (p = 0.08). When direct comparing, the A/G genotype was less common in the OXT promoter region in controls (p = 0.09) and in subjects with lactase persistence (p = 0.03) compared to subjects with lactase non-persistence. When healthy controls were viewed according to their own LCT-13910 genotypes, the C/C lactase non-persistent controls had a higher frequency for the OXT promoter A/G genotype than LCT-13910 T/T lactase persistent controls (41.2% vs 13.1%).No significant differences in frequencies of the investigated OXTR SNPs were noted in this study.. The results suggest that polymorphism in the promoter region of the OXT gene is most common in subjects with lactase non-persistence. This polymorphism may not be related to GI symptoms, as it is related to lactase non-persistence also in healthy controls.

Topics: Adult; Aged; Alleles; Breath Tests; DNA; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Irritable Bowel Syndrome; Lactase; Male; Middle Aged; Oxytocin; Polymorphism, Genetic; Young Adult