Thermal Integrative Stimuli for Assessment of Neuropathic Pain after SCI

描述（由申请人提供）： 慢性神经性疼痛是脊髓损伤（SCI）的一种特别麻烦的继发性后果，其影响约40%的SCI患者。尽管SCI相关的神经性疼痛的患病率很高，并且其对康复工作的影响很大，但目前对这种类型疼痛的治疗通常无效。中枢神经性疼痛的更成功的干预措施的发展受到以下事实的限制，即负责这种类型的疼痛的机制尚未明确理解，并且尚未建立明确的诊断和结果工具。定量感觉测试（QST），它允许在人类受试者的躯体感觉处理机制的非侵入性评价，最近被提倡作为一个潜在的关键工具，用于神经性疼痛的调查，包括帮助正在进行的疼痛评级的验证，在治疗效果的评价，并在成功的翻译研究从动物模型到临床治疗范例。拟议的试点项目的目标是检查具体的QST措施，这是为了评估的完整性，热和疼痛的综合感觉处理，在SCI患者的神经病理性疼痛的特点进行评估的效用。因为在这个试点研究中采用的方法已经在非常有限的出版物中报道，进行这个试点项目的基本原理是为下面概述的假设提供初步支持，这将指导设计一个完整的研究方案，以彻底验证这些QST技术在SCI神经性疼痛。 目标1：检查热伤害性刺激的空间整合程度与SCI患者神经病理性疼痛的存在之间的关系。通过要求受试者对使用一个热探头（9 cm 2面积）和使用两个并排热探头（总面积18 cm 2）递送的不同温度的热刺激产生的疼痛强度进行评级，测量刺激-反应关系。将通过比较受试者之间小刺激区域（一个探头）和大刺激区域（两个探头）的疼痛强度评级差异来评估空间总和。我们假设，患有SCI和神经性疼痛的参与者（即，更大的空间总和）相比，与SCI的参与者谁没有疼痛，这表明增强整合有害输入跨空间的人谁有神经性疼痛。 目标二：比较SCI和神经性疼痛患者与没有疼痛的SCI患者对“热格栅”刺激的感知反应。热格栅刺激将用于评估热和疼痛整合过程。热格栅通常由同时呈现的许多交错的温暖（40 ℃）和凉爽（20 ℃）刺激条组成，当呈现给具有完整体感功能的人的皮肤时，产生矛盾的“烧灼痛”感觉。这种由于热格栅引起的疼痛的经历在患有神经性疼痛的人中被认为是异常的。在拟议的初步研究中，将在SCI和神经性疼痛患者以及没有神经性疼痛的SCI患者中获得热格栅产生的疼痛阈值。假设患有神经性疼痛的参与者的热格栅阈值将显著高于没有神经性疼痛的参与者，这表明来自热和冷感觉通路的信息的正常整合在患有神经性疼痛的参与者中被破坏。 从拟议的试点研究的结果将产生洞察力的具体躯体感觉系统的机制，可能与神经性疼痛的经验，并将提供支持，为未来的研究，旨在充分验证使用这些QST技术作为潜在的诊断和结果的措施，神经性疼痛在SCI。

DESCRIPTION (provided by applicant): Chronic neuropathic pain is a particularly troublesome secondary consequence of spinal cord injury (SCI) which affects approximately 40% of persons with SCI. Despite the high prevalence of SCI-related neuropathic pain and its impact on rehabilitation efforts, current treatments for this type of pain are often ineffective. The development of more successful interventions for central neuropathic pain is limited by the fact that the mechanisms responsible for this type of pain are not clearly understood, and definitive diagnostic and outcome tools have yet to be established. Quantitative sensory testing (QST), which allows for noninvasive evaluation of somatosensory processing mechanisms in human subjects, has recently been advocated as a potentially critical tool for the investigation of neuropathic pain, including aiding in the validation of ratings of ongoing pain, in the evaluation of treatment efficacy, and in the successful translation of research from animal models to clinical treatment paradigms. The goal of the proposed pilot project is to examine the utility of specific QST measures, which are aimed at assessing the integrity of thermal and pain integrative sensory processing, for the assessment of neuropathic pain characteristics in persons with SCI. Because the methods to be employed in this pilot study have been reported in a very limited number of publications, the rationale for conducting this pilot project is to provide initial support for the hypotheses outlined below, which will guide the design of a full research protocol to thoroughly validate these QST techniques for neuropathic pain in SCI. Objective 1: Examine the relationship between the degree of spatial integration of thermal noxious stimulation and the presence of neuropathic pain in persons with SCI. Stimulus-response relationships will be measured by asking subjects to rate the intensity of pain produced by thermal stimuli of varying temperatures delivered using one thermal probe (9cm2 area) and those delivered using two thermal probes side-by-side (18cm2 total area). Spatial summation will be assessed by comparing the differences in pain intensity ratings for the small stimulus area (one probe) and the large stimulus area (two probes) across subjects. We hypothesize that greater differences in pain ratings between the two stimulus sizes (one probe vs. two probes) will occur in participants with SCI and neuropathic pain (i.e., greater spatial summation) compared to participants with SCI who do not have pain, suggesting enhanced integration of noxious inputs across space in persons who have neuropathic pain. Objective 2: Compare perceptual responses to the "thermal grill" stimulus between persons with SCI and neuropathic pain and persons with SCI who do not have pain. A thermal grill stimulus will be used to assess thermal and pain integration processes. The thermal grill, which is typically composed of a number of interlaced warm (40oC) and cool (20oC) stimulus bars presented simultaneously, produces a paradoxical "burning pain" sensation when presented to the skin of a person with intact somatosensory function. This experience of pain due to the thermal grill has been suggested to be abnormal in persons with neuropathic pain. In the proposed pilot study thermal grill-produced pain thresholds will be obtained in persons with SCI and neuropathic pain and in persons with SCI who do not have neuropathic pain. It is hypothesized that the thermal grill threshold for participants with neuropathic pain will be significantly higher than for participants without neuropathic pain, suggesting that the normal integration of information from warm and cool sensory pathways is disrupted in those with neuropathic pain. Results from the proposed pilot studies will yield insight regarding the specific somatosensory system mechanisms that may be related to the experience of neuropathic pain, and will provide support for future studies aimed at fully validating the use of these QST techniques as potential diagnostic and outcome measures for neuropathic pain in SCI.