Safety and Efficacy Study of PEA and Polydatin on Intestinal Inflammation and Visceral Hyperalgesia in IBS Patients

Irritable Bowel Syndrome

IBS, mast cell activation, low grade inflammation, visceral hyperalgesia

Despite the pathophysiology of IBS remains largely unsettled, several mechanisms have been proposed to explain symptom generation. These include psychosocial factors, altered gastrointestinal motor function and altered perception of visceral stimuli because of chronic low-grade inflammation and increased nociceptive mediator release by inflammatory cells, particularly mast cells. The aim of this pilot study is to provide evidence of: 1. intestinal mast cell (MC) infiltration and activation in IBS patients; 2. down-modulation of MC activation by the oral administration of the association of palmitoylethanolamide (PEA) and polydatin in IBS patients.

The number of inflammatory cells in the gut wall of IBS patients is increased in comparison to asymptomatic controls. A significant increase in the number of both mast cells and T-lymphocytes in the mucosa of IBS patients have been reported. Electron microscopic studies demonstrated that mast cells were more frequently degranulated in IBS, suggesting their increased state of activation. Accordingly, an increased mucosal release of preformed mediators, such as histamine and tryptase, as well as de novo synthesis and secretion of arachidonic acid end products (e.g. prostaglandin E2) have been demonstrated. These mediators are known to target sensory nerve pathways, including those innervating the gastrointestinal tract, leading to visceral hyperalgesia. Electron microscopic studies showed that the mean distance between inflammatory cells and enteric nerves is significantly reduced in IBS patients, thus providing a conceptual basis for a putative pathogenetic role of low-grade inflammation on sensory-motor dysfunction in IBS. Activated mast cells in close proximity to mucosal colonic innervation correlated with the frequency and severity of abdominal pain. Evidence that mast cell mediators of IBS patients, but not controls, evoked activation of nociceptive sensory afferent neurons are available, thus providing a possible mechanism through which mast cells can evoke pain in IBS patients. Similar results has been recently reported following the administration into the rat colon of supernatants collected from human IBS colonic biopsy samples in culture. This nociceptive effect on murine sensory neurons was inhibited by serine protease inhibitors and a Protease Activating Receptor-2 antagonist.

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