Sensory Mechanisms and Self-Injury

描述(由申请人提供)：对智力和发育障碍(IDD)患者慢性自残行为(SIB)的感觉和神经生物学基础知之甚少。在SIB的行为模型中，感觉机制起着积极或消极的自动强化作用，但很少有证据直接将行为机制和生物学机制联系起来。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一假设，即某些形式的SIB可能受到改变的疼痛机制的调节。从我们和其他人的工作中，我们知道疼痛可以导致这一人群的SIB，但我们几乎不知道慢性SIB是否会导致疼痛以及由此产生的神经免疫级联效应。大量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病理性疼痛假说，并指出疼痛和炎症/免疫活动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病理性疼痛有关。我们假设，将会有一组慢性SIB患者显著地(A)改变外周感觉转换，(B)炎症和免疫活性增加，以及(C)免疫介导的类似疾病的行为增加。采用病例对照设计，对40例有SIB和40例无SIB的IDD儿童进行匹配(年龄、性别、智商)比较。两组将在(A)外周神经支配(目标1)、(B)炎症/免疫细胞因子和相关多肽(目标2)和(C)类似疾病行为的功能指标(包括适应/社交行为、睡眠/饮食、感觉反应和疼痛迹象/症状)以及在SIB组内功能和结构变量的比较(目标3)的指标上进行比较。我们的初步结果表明，至少在外围，正在进行的神经免疫相互作用可能在一定程度上与迄今尚不清楚的慢性自我损伤的病理生理学有关。这项研究将提供第一次系统研究IDD儿童中与SIB相关的神经免疫变量的机会。

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.