Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity. Issue 10 (25th July 2014)

• Record Type: Journal Article
• Authors: Buhner, Sabine; Braak, Breg; Li, Qin; Kugler, Eva Maria; Klooker, Tamira; Wouters, Mira; Donovan, Jemma; Vignali, Sheila; Mazzuoli‐Weber, Gemma; Grundy, David; Boeckxstaens, Guy; Schemann, Michael
• Is Part Of: Experimental physiology. Volume 99:Issue 10(2014:Oct.)
• Page Start: 1299
• Page End: 1311
• Publication Date: 2014-07-25
• Subjects: Physiology, Experimental -- Periodicals; 571.0724
• DOI: 10.1113/expphysiol.2014.080036
• Languages: English
• ISSNs: 0958-0670

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="eph1475-sec-0010" sec-type="section"> <title>New Findings</title> <p> <list id="eph1475-list-0001" list-type="bullet"> <list-item> <p> <bold>What is the central question of this study?</bold> </p> <p>Supernatants from colonic mucosal biopsies from patients with irritable bowel syndrome (IBS) activate enteric and dorsal root ganglion (DRG) neurons. Based on the discomfort/pain threshold during rectal distension, IBS patients may be subtyped as normo‐ or hypersensitive. However, the link between neuronal activation and visceral sensitivity remains unknown.</p> </list-item> <list-item> <p> <bold>What is the main finding and its importance?</bold> </p> <p>We found that supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons than supernatants from normosensitive IBS patients. The level of activation correlated with the individual discomfort/pain threshold pressure values. We therefore conclude that mucosal biopsy supernatants have biomarker potential and may, in the future, help to personalize treatment of IBS patients with different visceral sensitivities.</p> </list-item> </list> </p> </sec> <sec id="eph1475-sec-0020" sec-type="section"> <p>Based on the discomfort/pain threshold during rectal distension, irritable bowel syndrome (IBS) patients may be subtyped as normo‐ or hypersensitive. We previously showed that mucosal biopsy supernatants from IBS patients activated enteric and visceral afferent neurons. We tested the hypothesis that visceral sensitivity is linked to the degree of neuronal activation. Normo‐ and hypersensitive IBS patients were distinguished by their discomfort/pain threshold to rectal balloon distension with a barostat. Using potentiometric and Ca<sup>2+</sup> dye imaging, we recorded the response of guinea‐pig enteric submucous and mouse dorsal root ganglion (DRG) neurons, respectively, to mucosal biopsy supernatants from normosensitive (<italic>n</italic> = 12 tested in enteric neurons, <italic>n</italic> = 9 tested in DRG) and hypersensitive IBS patients (<italic>n</italic> = 9, tested in both types of neurons). In addition, we analysed the association between neuronal activation and individual discomfort/pain pressure thresholds. The IBS supernatants evoked Ca<sup>2+</sup> transients in DRG neurons and spike discharge in submucous neurons. Submucous and DRG neurons showed significantly stronger responses to supernatants from hypersensitive IBS patients as reflected by higher spike frequency or stronger [Ca<sup>2+</sup>]<sub>i</sub> transients in a larger proportion of neurons. The neuroindex as a product of spike frequency or [Ca<sup>2+</sup>]<sub>i</sub> transients and proportion of responding neurons correlated significantly with the individual discomfort/pain thresholds of the IBS patients. Supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons. The level of activation correlated with the individual discomfort/pain threshold pressure values. These findings support our hypothesis that visceral sensitivity is linked to activation of peripheral neurons by biopsy supernatants.</p> </sec> </abstract>