MECHANISMS OF CENTRAL AND PERIPHERAL HYPERALGESIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肠易激综合征(IBS)是一种常见的胃肠道疾病，以慢性腹痛和肠道功能改变(腹泻和/或便秘)为特征。据估计，IBS影响了20%的美国人口。虽然IBS的病理生理机制尚不清楚，但内脏高敏感性(即对肠道扩张的反应痛阈值降低)是大多数IBS患者存在的疾病的临床标志。然而，导致慢性内脏高敏感性的机制目前尚不清楚。我们的实验室已经获得证据表明，IBS患者也表现出对实验性热疼痛刺激的躯体过敏反应(1-4)。这些新发现与以前的研究不同，以前的研究表明IBS相关的超敏反应仅限于肠道(5-9)。相反，我们的数据表明，IBS的特征是中枢疼痛处理过程中更广泛的变化(10)。基于我们的初步数据，我们提出了新的机械假说，即IBS患者对躯体伤害性刺激具有普遍但分级的超敏反应。我们预计，这种躯体超敏反应是体表组织的，因此与结肠共享内脏器官会聚的下部皮肤体表现出最强的超敏反应。此外，我们提出，对于深层的紧张性刺激，超敏反应将比对于浅表的短暂刺激更大。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel function (diarrhea and/or constipation). IBS is estimated to affect 20% of the United States population. Although the pathophysiology of IBS is unknown, visceral hypersensitivity (i.e., decreased pain thresholds in response to gut distension) is a clinical marker of the disorder present in the majority of patients with IBS. The mechanisms that lead to chronic visceral hypersensitivity, however, are currently unknown. Our laboratory has acquired evidence that patients with IBS also display somatic hypersensitivity in response to experimental thermal pain stimuli (1-4). These new findings differ from previous investigations that indicated IBS-associated hypersensitivity is limited to the gut (5-9). In contrast, our data suggest that IBS is characterized by more widespread alterations in central pain processing (10). Based on our preliminary data, we propose the novel, mechanistic hypothesis that IBS patients have a generalized but graded hypersensitivity to somatic nociceptive stimuli. We anticipate that this somatic hypersensitivity is somatotopically organized such that the lower dermatomes that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. Moreover, we propose that the hypersensitivity will be greater for deep, tonic stimuli than for superficial, brief stimuli.