Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, Clinical Neurology, Neurosciences, Neurosciences & Neurology, (low-grade) inflammation, food antigens, pain, TRP channels, MUCOSAL BIOPSY SUPERNATANTS, PLACEBO-CONTROLLED TRIAL, GUANYLATE-CYCLASE-C, VISCERAL SENSITIVITY, IMMUNE ACTIVATION, ABDOMINAL-PAIN, RAT MODEL, COLONIC HYPERSENSITIVITY, MAST-CELLS, INTESTINAL-MUCOSA, Abdominal Pain, Animals, Gastrointestinal Diseases, Humans, Irritable Bowel Syndrome, Mast Cells, Neuroimmunomodulation, Neurons, Pain Perception, 1103 Clinical Sciences, 1109 Neurosciences, 1116 Medical Physiology, 3202 Clinical sciences, 3208 Medical physiology, 3209 Neurosciences

Abstract:

Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders (FGIDs). Visceral pain stimuli are perceived and transmitted by afferent neurons residing in the dorsal root ganglia that have sensory nerve endings in the gut wall and mesentery. Accumulating evidence indicates that peripheral activation and sensitization of these sensory nerve endings by bioactive mediators released by activated immune cells, in particular mast cells, can lead to aberrant neuroimmune interactions and the development and maintenance of visceral hypersensitivity. Besides direct neuronal activation, low concentrations of proteases, histamine, and serotonin can chronically sensitize nociceptors, such as TRP channels, leading to persistent aberrant pain perception.