Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome

Cremon, Cesare; Stanghellini, Vincenzo; Barbaro, Maria Raffaella; Cogliandro, Rosanna; Bellacosa, Lara; Santos, Javier; Vicario, María; Pigrau, Marc; Alonso-Cotoner, Carmen; Lobo, Beatriz; Azpiroz, Fernando; Varannes, Stanislas Bruley des; Neunlist, Michel; DeFilippis, David; Iuvone, Teresa; Petrosino, Stefania; Marzo, Vincenzo Di; Barbara, Giovanni

doi:10.1111/apt.13958

Cited by 89 publications

(94 citation statements)

References 41 publications

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“…19,40 In this study, we focused on CB 2 , because it is expressed peripherally, is an established constituent of immune system cells, and is upregulated during inflammation. 41 The fact that the increase in CB 2 expression was not specific to any IBS bowel habit subgroup is in line with a recent study by Cremon et al, 42 showing an increased expression of CB 2 receptors in mucosal biopsies of IBS patients regardless of bowel habit. This could reflect a link to a particular immune reaction activation.…”

Section: Moreover Tnfα Induces Mor Expression In Primary T Cells By Asupporting

confidence: 83%

µ‐opioid receptor, β‐endorphin, and cannabinoid receptor‐2 are increased in the colonic mucosa of irritable bowel syndrome patients

Dothel

Chang

Shih

et al. 2019

Neurogastroenterology Motil

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Background and Aims The gut immune, cannabinoid, and opioid systems constitute an integrated network contributing to visceral sensation and pain modulation. We aimed to assess the expression of the µ‐opioid receptor (MOR), its ligand β‐endorphin (β‐END), and cannabinoid receptor‐2 (CB2) in patients with irritable bowel syndrome (IBS) and asymptomatic controls (AC) and their correlation with sex and symptom perception. Methods Mucosal biopsies were obtained from the left colon of 31 IBS patients (45% women) with predominant constipation (IBS‐C, 9) or diarrhea (IBS‐D, 10) or with mixed bowel habits (IBS‐M, 12) and 32 AC (44% women) and processed for qRT‐PCR, Western blotting, and immunohistochemistry. Key Results µ‐opioid receptor and CB2 mRNA and protein expression and β‐END protein levels were increased in patients with IBS compared to AC (all Ps=0.021). A significant sex by IBS interaction was found in relation to CB2 mRNA expression (P = .003) with women showing a markedly higher expression to men (P = .035). In contrast, in AC, men had higher expression than women (P = .033). β‐END, MOR, and CB2 immunoreactivities (IR) were localized to CD4+T cells including EMR‐1+ eosinophils and CD31+ T cells but not to mast cells. Conclusions The increased expression of MOR, β‐END, and CB2 in the mucosa of IBS patients, where they are localized to immune cells, suggests that opioid and cannabinoid systems play an immune‐related compensatory role in visceral pain in IBS patients. Further work is necessary to support this hypothesis.

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Section: Moreover Tnfα Induces Mor Expression In Primary T Cells By Asupporting

confidence: 83%

µ‐opioid receptor, β‐endorphin, and cannabinoid receptor‐2 are increased in the colonic mucosa of irritable bowel syndrome patients

Dothel

Chang

Shih

et al. 2019

Neurogastroenterology Motil

Self Cite

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“…In some cases, the clinical improvement of symptoms was clearly correlated with the control of mast cell activation [ 148 ]. A recent clinical trial assessed the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in IBS, reporting an improvement of abdominal pain severity (ClinicalTrials.gov number, NCT01370720) [ 149 ]. However, no changes in mast cells numbers or in the mast cell activation profile were observed [ 149 ].…”

Section: Nutraceuticals Affecting Mast Cell Activitymentioning

confidence: 99%

“…A recent clinical trial assessed the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in IBS, reporting an improvement of abdominal pain severity (ClinicalTrials.gov number, NCT01370720) [ 149 ]. However, no changes in mast cells numbers or in the mast cell activation profile were observed [ 149 ]. Therefore, the link between the positive clinical effects and the potential modulation of mast cells is still a question and further studies are required to elucidate the mechanism of action of palmitoylethanolamide/polydatin in IBS.…”

Section: Nutraceuticals Affecting Mast Cell Activitymentioning

confidence: 99%

Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

2020

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Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.

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“…A 12-week trial in 54 IBS patients observed that a food additive containing PEA with polydatin (200 mg/20 mg), which may also stabilize mast cells, improved abdominal pain more than placebo. [48] Whether these effects are mediated via mast cells or PPAR-alpha-receptors on enteric glial cells, which have also been implicated in animal models of postoperative ileus and IBS is unclear. [49,50] Indeed, activation of PPAR-alpha receptors in enteric glia by PEA improves colon inflammation through enteric glia/toll like receptor 4-dependent PPAR-alpha activation.…”

Section: Diarrhea and Diarrhea-predominant Ibs (Ibs-d)mentioning

confidence: 99%

Existing and emerging therapies for managing constipation and diarrhea

Bharucha

Wouters

Tack

2017

Current Opinion in Pharmacology

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Functional bowel disorders (i.e., constipation and diarrhea) are characterized by abdominal pain, bloating, distention, and/or bowel habit abnormalities in the absence of obvious anatomic or physiologic abnormalities on routine diagnostic tests. These symptoms are attributable to gastrointestinal sensorimotor dysfunctions resulting from peripheral and/or central mechanisms. Available drugs target the underlying bowel disturbance (ie, constipation, diarrhea, or both), supplemented when necessary by management of pain. Osmotic and stimulant laxatives, secretagogues, and serotonin 5-HT4 receptor agonists are approved for treating constipation. Loperamide, anticholinergic agents, rifaximin, bile-acid binding agents, eluxadoline, and clonidine are used to treat diarrhea. Several exciting new compounds, some of which have been evaluated in humans, are currently under development.

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Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome

Cited by 89 publications

References 41 publications

µ‐opioid receptor, β‐endorphin, and cannabinoid receptor‐2 are increased in the colonic mucosa of irritable bowel syndrome patients

µ‐opioid receptor, β‐endorphin, and cannabinoid receptor‐2 are increased in the colonic mucosa of irritable bowel syndrome patients

Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

Existing and emerging therapies for managing constipation and diarrhea

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