Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity
Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity
复制标题
DOI：
10.1113/expphysiol.2014.080036
复制
发表时间：
2014-10-01
影响因子：
2.7
通讯作者：
Schemann, Michael
中科院分区：
文献类型：
--
作者：
Buhner, Sabine;Braak, Breg;Schemann, Michael
根据直肠扩张期间的不适/疼痛阈值，肠易激综合征（IBS）患者可分为正常或过敏亚型。我们以前发现，肠易激综合征患者的粘膜活检上清液激活肠和内脏传入神经元。我们检验了内脏敏感性与神经元激活程度相关的假设。正常和过敏性IBS患者通过他们对直肠气囊扩张的不适/疼痛阈值来区分。使用电位和Ca 2+染料成像，我们分别记录了豚鼠肠粘膜下和小鼠背根神经节（DRG）神经元对正常敏感（肠神经元n = 12，DRG n = 9）和过敏性IBS患者（n = 9，两种类型的神经元）的粘膜活检上清液的反应。此外，我们分析了神经元激活和个人不适/疼痛压力阈值之间的关联。IBS上清诱发DRG神经元钙瞬变和粘膜下神经元锋电位放电。粘膜下和DRG神经元对来自过敏性IBS患者的上清液显示出显著更强的反应，如在更大比例的神经元中更高的尖峰频率或更强的[Ca 2 +]（i）瞬变所反映的。神经指标作为尖峰频率或[Ca 2 +]（i）瞬变和响应神经元的比例的乘积，与IBS患者的个体不适/疼痛阈值显著相关。过敏性IBS患者的上清液引起肠和DRG神经元更强的激活。激活水平与个体不适/疼痛阈值压力值相关。这些发现支持我们的假设，内脏敏感性与周围神经元的激活活检上清液。
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 Ca2+ 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 (n = 12 tested in enteric neurons, n = 9 tested in DRG) and hypersensitive IBS patients (n = 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 Ca2+ 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 [Ca2+](i) transients in a larger proportion of neurons. The neuroindex as a product of spike frequency or [Ca2+](i) 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.