Sensory Mechanisms and Self-Injury

描述（由申请人提供）：对于智力和发育障碍（IDD）患者慢性自伤行为（SIB）的感觉和神经生物学基础知之甚少。在SIB的行为模型中，感觉机制被认为是积极或消极的自动强化因素，但很少有证据表明行为机制和生物机制之间存在直接联系。来自慢性疼痛及其行为后遗症的临床和动物研究的证据支持这样的假设，即某些形式的SIB可能受到改变的疼痛机制的调节。从我们的工作和其他人的工作中，我们知道疼痛可以导致这个人群的SIB，但我们几乎不知道慢性SIB是否会导致疼痛和由此产生的神经免疫级联效应。已建立的临床前和临床文献以及研究者的初步数据初步支持慢性SIB的工作感觉功能障碍和神经性疼痛样假设，并指出疼痛和炎症/免疫活性的外周和中枢机制的重要作用。该项目的目的是开始测试一种新的SIB模型，该模型与炎症和免疫系统激活引起的慢性神经性疼痛有关。我们假设将有一个慢性SIB患者亚组具有显著的(a)外周感觉创新改变，(b)炎症和免疫活性增加，以及(c)免疫介导的“疾病”样行为增加。病例对照设计将用于比较有（n = 40）和没有SIB （n = 40）的IDD患儿的匹配（年龄、性别、智商）组。各组将在以下方面进行比较：(a)外周神经分布（目标1），(b)炎症/免疫细胞因子和相关肽（目标2），(c)“疾病”样行为的功能指标，包括适应/社会行为、睡眠/饮食、感觉反应性和疼痛体征/症状，以及SIB组内功能和结构变量的比较（目标3）。我们的初步结果表明，至少在外周，正在进行的神经免疫相互作用可能在一定程度上与慢性自伤的病理生理学有关。这项研究将首次提供机会系统地调查与IDD儿童SIB相关的神经免疫变量。

DESCRIPTION (provided by applicant): Little is known about the sensory and neurobiological basis of chronic self-injurious behavior (SIB) among individuals with intellectual and developmental disabilities (IDD). In behavioral models of SIB, sensory mechanisms function as putative positive or negative automatic reinforcers but there is little evidence directly linking behavioral and biological mechanisms. Evidence from both clinical and animal studies of chronic pain and its behavioral sequelae supports the hypothesis that some forms of SIB may be regulated by altered pain mechanisms. From our work and that of others, we know that pain can lead to SIB in this population but we know almost nothing about whether chronic SIB leads to pain and the resulting neuro-immune cascade of effects. An established body of preclinical and clinical literature and the investigator's preliminary data provide initial support for a working sensory dysfunction and neuropathic-pain like hypothesis of chronic SIB and point to an important role for the peripheral and central mechanisms of pain and inflammatory/immune activity. The purpose of this project is to begin testing a novel model of SIB in relation to chronic neuropathic-like pain due to inflammatory and immune system activation. We hypothesize that there will be a subgroup of individuals with chronic SIB that have significantly (a) altered peripheral sensory innveration, (b) increased inflammatory and immune activity, and (c) increased immune-mediated 'sickness' like behavior. A case-control design will be used to compare matched (age, gender, IQ) groups of children with IDD with (n = 40) and without SIB (n = 40). The groups will be compared on measures of (a) peripheral innervation (Aim 1), (b) inflammatory/immune cytokines and related peptides (Aim 2), and (c) functional indicators of 'sickness'-like behavior including adaptive/social behavior, sleeping/eating, and sensory reactivity and pain signs/symptoms as well as within SIB group comparisons of functional and structural variables (Aim 3). Our preliminary results suggest that, at least in the periphery, ongoing neuro-immune interactions may, in part, be related to the as of yet poorly understood pathophysiology of chronic self-injury. This study will provide the first opportunity to systematically investigate neuro-immune variables in relation to SIB among children with IDD.