PAIN REGULATORY SYSTEM DYSFUNCTION IN CHRONIC PAIN

静息血压（BP）升高一贯与急性疼痛敏感性降低有关。朱鹮心血管相关抗痛觉作用（部分由内源性阿片类药物介导）是健康个体适应疼痛的重要组成部分。目前尚不清楚这些抗感觉机制是否在慢性疼痛患者中正常运作。先前的研究表明慢性疼痛患者的内源性阿片类药物水平存在缺陷，尽管对这些缺陷的功能影响（如镇痛能力减弱）知之甚少。鉴于内源性阿片类药物在心血管相关抗痛觉和慢性疼痛条件下可能的阿片类药物缺陷中的中介作用，我们假设慢性疼痛患者将表现出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本质。提高对慢性疼痛机制的理解有可能改善慢性疼痛患者的治疗。这些研究的具体目的有三个：1)比较神经性和伤害性慢性疼痛患者与正常人的静息血压和急性疼痛敏感性之间的关系；2)比较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的内源性阿片介导程度的可能差异；3)研究慢性疼痛的内源性阿片功能障碍是否进行性，因此是否与疼痛持续时间有关。60例慢性疼痛患者（研究1 =神经性背痛，研究2=伤害性背痛）和60名健康对照者分别接受一次安慰剂组和一次纳洛酮阿片类药物阻断组的实验室缺血性疼痛刺激（随机、平衡顺序）。在两个疗程中，静息血压将在基线时测定。疼痛患者也会在给药前后评估他们的临床疼痛。预计对照组在静息血压和急性疼痛敏感性之间会显示出显著的负相关，这至少部分被纳洛酮消除。疼痛患者的静息血压与急性疼痛反应性无相关性或正相关性，并且对阿片类药物阻断无反应。在阿片类药物阻断反应中，更长的疼痛持续时间预计与较小的血压/疼痛关系变化相关。

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.