PAIN REGULATORY SYSTEM DYSFUNCTION IN CHRONIC PAIN

静息血压（BP）升高始终与急性疼痛敏感性降低相关。朱鹭心血管相关的抗伤害感受（部分由内源性阿片类物质介导）是健康个体适应疼痛的重要组成部分。尚不清楚这些抗伤害感受机制是否在慢性疼痛患者中正常发挥作用。先前的研究表明慢性疼痛患者的内源性阿片样物质水平不足，尽管对功能影响知之甚少（例如，减少镇痛）的这些缺陷。考虑到内源性阿片类物质在心血管相关抗伤害感受中的介导作用以及慢性疼痛条件下可能的阿片类物质缺陷，假设慢性疼痛患者将显示这些正常适应性心血管疼痛调节关系的改变。这些研究的长期目标是探索慢性疼痛患者内源性疼痛调节系统功能障碍的性质。对慢性疼痛机制的进一步了解有可能改善对慢性疼痛患者的治疗。这些研究的具体目标有三个：1）检查与正常人相比，神经性和伤害性慢性疼痛患者中静息血压和急性疼痛敏感性之间的关系，2）检查疼痛患者和正常对照亚组中静息血压和急性疼痛敏感性之间关系的内源性阿片样物质介导程度的可能差异，和3）检查慢性疼痛中的内源性阿片样物质功能障碍是否是进行性的并因此与疼痛持续时间相关。60名慢性疼痛患者（研究1 =神经性背痛，研究2=伤害性背痛）和60名健康对照将经历实验室缺血性疼痛刺激，一次在安慰剂下，一次在用纳洛酮的阿片样物质阻断下（随机化，平衡顺序）。在这两个阶段中，将在基线时测定静息血压。疼痛患者还将在给药前后评定其临床疼痛。预期对照将显示静息BP和急性疼痛敏感性之间的显著负相关，其至少部分被纳洛酮消除。疼痛患者预期静息血压与急性疼痛反应性之间无相关性或呈正相关性，并且对阿片类药物阻滞无反应。疼痛持续时间越长，阿片类药物阻滞后BP/疼痛关系的变化越小。

Elevated resting blood pressure (BP) is consistently related to diminished acute pain sensitivity. Ibis cardIovascular-related antinociception (mediated in part by endogenous opioids) is an important component of adaptation to pain in healthy individuals. it is unknown whether these antinociceptive mechanisms operate normally in chronic pain patients. Previous research indicates deficits in endogenous opioid levels in chronic pain patients, although little is known about the functional impact (e.g., diminished analgesia) of these deficits. Given the mediating role of endogenous opioids in cardiovascular-related antinociception and likely opioid deficits in chronic pain conditions, it is hypothesized that chronic pain patients will display alterations in these normally adaptive cardiovascular-pain regulatory relationships. The long-term objective of these studies is to explore the nature of dysfunction in the endogenous pain regulatory systems of chronic pain patients. improved understanding of the mechanisms contributing to chronic pain has the potential to lead to improved treatment for chronic pain patients. The specific aims of these studies are threefold: 1) examine the relationship between resting blood pressure and acute pain sensitivity in both neuropathic and nociceptive chronic pain patients as contrasted to normals, 2) examine possible differences in degree of endogenous opioid mediation of the relationship between resting blood pressure and acute pain sensitivity across the pain patient and normal control subgroups, and 3) examine whether endogenous opioid dysfunction in chronic pain is progressive and therefore related to pain duration. Sixty chronic pain patients (study l=neuropathic back pain, study 2=nociceptive back pain) and 60 healthy controls will undergo a laboratory ischemic pain stimulus once under placebo and once under opioid blockade with naloxone (randomized, counterbalanced order). in both sessions, resting BP will be determined at baseline. Pain patients will also rate their clinical pain before and after drug administration. it is expected that controls will display significant negative correlations between resting BP and acute pain sensitivity, which is at least partially eliminated by naloxone. Pain patients are expected to demonstrate no correlation or a positive correlation between resting BP and acute pain responsiveness, and will be unresponsive to opioid blockade. Greater pain duration is expected to be associated with smaller changes in the BP/pain relationship in response to opioid blockade.