IBS and Autonomic Nervous System Responses to Pain

Irritable bowel syndrome (IBS) is one of the most commonly encountered medical problems in the United States with an estimated prevalence of 9% to 22%.1 This disorder is more frequently seen in women than in men, with the peak prevalence occurring in the third and fourth decades of life. IBS accounts for approximately 12% of visits to primary care physicians and 28% to 33% of referrals to gastroenterologists.2–4 IBS significantly impacts patients in a number of ways. For example, IBS significantly reduces patients' quality-of-life.5,6 In addition, IBS imposes a significant economic burden to patients and to our health care system. Patients with IBS have more frequent physician visits, undergo more tests, have increased rates of unnecessary surgery, and use more medications than non-IBS patients.4,7,8 These factors all contribute to the significant expense of diagnosing and treating patients with IBS, currently estimated at 15 to 30 billion dollars per year.9,10 Although the exact etiology of IBS remains unknown, a commonly accepted view is that IBS symptoms develop because of 3 major pathophysiologic processes. First, IBS patients may experience disordered motility in the gastrointestinal (GI) tract. Some patients with IBS have abnormalities in the migratory motor complex, which may lead to either delayed (constipation) or accelerated (diarrhea) intestinal transit.11 Other IBS patients have very high amplitude propagating contractions within the colon, or discrete clustered contractions in the small intestine, both of which may be associated with episodes of abdominal pain.12,13 Second, patients with IBS have altered thresholds to pain within the GI tract and suffer from visceral hypersensitivity.14–16 In general, patients with IBS sense painful stimuli within the gut at much lower levels than non-IBS patients; in addition, patients with IBS may misinterpret normal GI physiology as painful. Third, several studies have shown that central nervous system processing of visceral sensory information is different than in healthy volunteers.17,18 These 3 pathophysiologic mechanisms, however, do not fully explain the myriad of symptoms expressed by IBS patients. As far back as 1928, some clinicians believed that the autonomic nervous system (ANS) played a role in the generation of IBS symptoms.19 More recent studies have shown some degree of autonomic dysfunction in subgroups of patients with functional bowel disorders, especially in IBS patients.20–22 Although both the study patients and the techniques used to measure ANS activity varied considerably from study to study, these results suggest that parasympathetic tone is increased and/or sympathetic tone is decreased in patients with increased motor activity (ie, IBS with diarrhea), whereas parasympathetic outflow is decreased and/or sympathetic outflow is increased in patients with decreased GI motility (ie, IBS with constipation). The role, and the response, of the ANS to pain in IBS patients have not been well studied, however. In the current issue of the Journal of Clinical Gastroenterology (pages 814 to 820) Tousignant-Laflamme and colleagues report on differences in ANS response to somatic pain in IBS patients. In this study, pain perception, galvanic skin response, and heart rate monitoring was performed in 27 women (14 with IBS and 13 age-matched healthy volunteers). Heart rate variability, including measurements of high frequency power (primarily a vagal influence on heart rate), and low frequency power (reflecting both parasympathetic and sympathetic influence), was assessed during a baseline period and during immersion of the left forefoot in cold water (7°C) for 2 minutes. The foot, rather than the upper extremity, was chosen because lumbar dermatomes share some sensory overlap with the colon. No differences were found in pain intensity ratings between patients and volunteers, which confirm earlier studies showing that somatic sensitivity is not different in IBS patients. However, heart rate variability analysis demonstrated differential responses in healthy volunteers compared with IBS patients in response to cold water immersion. Although the perception of pain was similar, the peak rise in heart rate was higher in healthy controls. Analysis of the low frequency/high frequency ratio revealed apparent increased sympathetic activity and decreased parasympathetic activity in healthy controls during the painful stimulus, whereas IBS patients had reduced sympathetic cardiac regulation and increased parasympathetic cardiac activity. These findings are intriguing because they may account for some IBS symptoms that have been difficult to explain with our current theories of pathogenesis. For example, patients with chronic functional abdominal pain often do not experience an increase in heart rate during an acute episode of abdominal pain. It is possible that this occurs because of an abnormal parasympathetic response. As well, vasomotor responses experienced by some IBS patients (warmth, flushing, and sweating), and other extraintestinal symptoms (migraine headaches, and fatigue) may also reflect autonomic dysfunction. Since most clinicians are now comfortable with the concept of the brain-gut axis, it is easy to envision how abnormal responses in the ANS, which links the central nervous system to the enteric nervous system, could produce a wide array of symptoms. These novel findings do not provide any insight into whether ANS dysfunction occurs first, with later development of IBS (more likely), or whether ANS dysfunction occurs due to long-standing IBS (less likely). However, this study reinforces other research data showing that some patients with IBS have ANS dysfunction. Future research studies are needed to determine whether fluctuating IBS symptoms are due to fluctuations in ANS function, whether symptoms of pos-infectious IBS develop as a result of ANS dysfunction, and whether targeted drug therapy can resolve these ANS changes.