乌鸦传媒

Pain is an important sign of disorder within the internal organs, and there are many dietary and pharmacological approaches to managing gastrointestinal (GI) diseases such as irritable bowel syndrome (IBS). A new review stresses the importance of effective therapies now and in the future, and appraises the medical treatment of abdominal pain in IBS through nutrition and prescribed drugs.¹

Michael Camilleri, MD, lead author of the review published in the May 2017 issue of Gut, reviewed the current evidence base for the management of abdominal pain in IBS.

“This new report sets out to evaluate the mechanisms involved in mediating abdominal pain in IBS, the mode of action of interventions to relieve such pain, and considers the available evidence for efficacy and safety of current medications,” Dr. Camilleri told 乌鸦传媒. “We also look to advances in the neurobiology of abdominal pain, to peer into the future development of approaches to treat abdominal pain in IBS,” he added.

Visceral sensations are often considered to be the same as visceral pain, yet visceral sensations do not always result in pain. For example, a stretched stomach wall can indicate fullness through a pleasant satiated feeling, whereas a severely overstretched stomach wall might lead to intense pain.² Sensory and pain information are conveyed from the gut to the central nervous system (CNS) by visceral afferents some of which reside in the sympathetic nervous system (SNS), part of the nervous system responsible for the body’s ‘flight-or-fight response.¹

According to the authors, evidence suggests that pain associated with IBS develops through different pathways: rectal pain is related to pelvic pathways whereas gut pain occurs via thoracolumbar spinal afferents, in particular, the vascular afferents.¹

“The gastrointestinal tract has a very rich innervation and several types of sensory nerve endings and nerves that send signals that alter the functions of the gut, as well as signals that ultimately reach the brain and conscious perception. Just as all roads lead to Rome (the brain), all sensory signals that are perceived by the brain start in the nerve endings in the gastrointestinal tract,” Dr. Camilleri said.

In IBS, symptoms present as abdominal pain and altered bowel function. However, patients with IBS also experience anxiety, and addressing the cause will assist in the provision of adequate pain relief. Abdominal symptoms are often linked to food or a deficiency of fiber in the diet, and current interventions include fiber supplements, low FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), and probiotics.¹

According to Camilleri, “Interactions between the gut microbiota, stress, and the central nervous system have emerged suggesting that visceral pain-related disorders may be candidates for symptom relief through therapeutic alterations of the microbiome." He added that "this is the rationale for the use of unabsorbable antibiotics or probiotics in the relief of abdominal pain.”

He also explained, “One of the plausible mechanisms of benefit is an alteration of the microbes in the colon which results in a change in the ability of the resident microbes to metabolize some of the unabsorbed foods, such as fiber, or complex carbohydrates like starch. Subsequently, this produces gas in the colon resulting in sensations of bloating, discomfort or pain.”

Pharmacological treatments for IBS

Various drug therapies are available to treat patients with IBS although these appear to have mixed results. With non-absorbed antibiotic therapy, urgency and bloating are significantly improved but there is no real benefit to abdominal pain, and the mechanism of benefit remains unclear. Antispasmodics are well tolerated and used to treat IBS across Europe. The authors of a European systematic review found an improvement in abdominal pain in 7 out of 9 studies, although these studies did not use standardized diagnostic criteria. A significant improvement in bowel symptoms was reported in 2 of the studies, and improvement in global symptom severity in another 4 studies.^1,3

The use of antidepressants has also been studied in the treatment of IBS. However, these reports have inconsistencies in their design and safety, raising significant questions about this class of therapeutic agents. One meta-analysis revealed that 31.3% of patients had adverse effects associated with antidepressant medication compared with 16.5% of the placebo group, and the long-term safety of these drugs for non-psychiatric symptoms is being called into question, although no studies to date have proved causality.¹

“Currently, available approaches have limited efficacy, and for many of them, the number needed to treat may be close to 6 or higher, meaning that 6 or more patients would need to be treated for one of those patients to have significant clinical benefit. The US Food and Drug Administration has issued cautions and recommendations regarding the use of some drugs, and there is an extensive off-label use of antidepressants and benzodiazepines for abdominal pain in patients with IBS,” Dr. Camilleri said.

“Although causation has not been established, there is epidemiological evidence of increased risk of dementia with long term (several years’) use of antidepressants of the SSRI class (but not tricyclic antidepressants) and benzodiazepines,” he said.  

A look to the future

A recent randomized controlled trial was designed to compare a low FODMAP with high FODMAP diet in patients with IBS to provide a mechanistic understanding of the disease. The results revealed that histamine levels and the microbiota of participants were altered, which may, in turn, modify patient symptoms.⁴ Another study evaluated a histamine receptor H1 (HRH1) antagonist after HRH1 was linked to visceral hypersensitivity, and results were positive for abdominal and overall pain relief.⁵ These results may provide a novel means for patient selection in the future. The detection of histamine in urine or other samples could be used to select patients who respond to HRH1 antagonists highlighting the need to identify biomarkers if progress in IBS treatment is to move forward.¹

“Advances in neurobiology of pain sensation and tissue expression provide clues to potential targets for future medical treatments of IBS. Until now, the targets thought to be genetic include SCN5A, which has rarely been reported in association with increased visceral pain or sensitivity, due to changes in the ion channel NAV 1.5,” said Dr. Camilleri. Given the increased exposure of patients to cannabinoids in search of pain relief, it is relevant that preliminary studies also suggest an association between the genes mediating cannabinoid 1 receptor function or cannabinoid metabolism, with colonic transit and pain sensation during acute colonic distensions.

He continued, “At present, it appears more likely that differences in the expression of important mediators of sensation in the intestinal tissues (particularly the receptors on nerve endings) are more promising targets for pain relief.”

Published: June 09, 2017