MECHANISMS OF CENTRAL AND PERIPHERAL HYPERALGESIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。肠易激综合征（IBS）是一种常见的胃肠道疾病，其特征是慢性腹痛和肠功能改变（腹泻和/或便秘）。据估计，IBS影响了20%的美国人口。虽然肠易激综合征的病理生理机制尚不清楚，但内脏超敏反应（即肠道膨胀引起的疼痛阈值降低）是大多数肠易激综合征患者的临床标志。然而，导致慢性内脏超敏反应的机制目前尚不清楚。我们的实验室已经获得证据表明，IBS患者对实验性热痛刺激也表现出躯体超敏反应（1-4）。这些新发现不同于先前的研究，先前的研究表明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的特点是中枢性疼痛处理发生了更广泛的改变（10）。基于我们的初步数据，我们提出了一种新的机制假设，即肠易激综合征患者对躯体伤害性刺激具有普遍但逐渐的超敏反应。我们预计这种躯体超敏反应是体位性组织的，与结肠共享脏器躯体会聚的下皮节表现出最大的超敏反应。此外，我们认为，深度、紧张性刺激比浅层、短暂刺激的超敏性更强。

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.