HYPERTENSION, RISK FOR HYPERTENSION AND HYPOALGESIA

这项研究的长期目标是评估痛觉减退作为高血压风险的生物行为标志物。该研究将检验痛觉减退和高血压有共同的病理生理学的假设（即，中枢阿片样物质敏感性降低），其特征在于内源性阿片样物质和脊髓上疼痛调节系统的增强的激活。在一定程度上，这一假设是正确的，个体差异的伤害性反应在休息时，在阿片类药物阻滞，并在脊髓上的激活可以用来预测血压的纵向变化。该项目的发现也可能有助于解释临床疼痛的减弱（例如，心绞痛），这可能使高血压患者心脏病的早期和准确检测复杂化。提出了三项研究，将使用伤害性屈曲反射（NFR），定义为引起腿撤回所需的腓肠神经刺激强度，作为伤害性感受的客观测量。研究1将确定对照组和未用药的新诊断高血压患者的NFR阈值，并将评估内源性阿片类药物和下行疼痛调制作为高血压痛觉减退的介质。研究2将确定高血压和低血压风险（由父母高血压史和静息血压定义）的年轻人的NFR阈值，还将评估内源性阿片类药物和下行疼痛调制作为高血压风险人群中痛觉减退的介质。研究3将评价静息时NFR阈值和响应于椎管上调节的NFR阈值变化，作为高血压和低血压风险年轻人血压纵向变化的预测因子。拟议的研究之所以重要，有几个原因。研究1和2将评估有前途的痛觉减退机制，这可能会导致重要的见解内源性阿片类药物在高血压的病理生理学的作用。研究3将评估伤害性反应，作为在高风险男性和女性的异质组中识别高血压风险最大者的一种手段。这些信息可用于确定行为和其他风险降低工作的最佳候选人。

The long-term objective of the proposed research is to evaluate hypoalgesia as a biobehavioral marker of risk for hypertension. The research will test the hypothesis that hypoalgesia and hypertension share a common pathophysiology (i.e., central opioid hyposensitivity) that is characterized by enhanced activation of endogenous opiates and supraspinal pain modulation systems. To the extent that this hypothesis is true, individual differences in nociceptive responses at rest, during opiate blockade, and during supraspinal activation may be used to predict longitudinal changes in blood pressure. The findings from this project may also help to explain the attenuation of clinical pain (e.g., angina) that can complicate early arid accurate detection of heart disease in individuals with hypertension. Three studies are proposed that will use the nociceptive flexion reflex (NFR), defined as the intensity of sural nerve stimulation required to elicit leg withdrawal, as an objective measure of nociception. Study l will determine NFR thresholds in controls and unmedicated patients with newly-diagnosed hypertension, and will assess endogenous opiates and descending pain modulation as mediators of hypertensive hypoalgesia. Study 2 will determine NFR thresholds in young adults at high and low risk for hypertension (defined by parental history of hypertension and resting blood pressure), and will also assess endogenous opiates and descending pain modulation as mediators of hypoalgesia in those at high risk for hypertension. Study 3 will evaluate NFR thresholds at rest and changes in NFR threshold in response to Supraspinal modulation as predictors of longitudinal changes in blood pressure in young adults at high and low risk for hypertension. The proposed studies are important for several reasons. Studies l and 2 will assess promising mechanisms of hypoalgesia which may lead to important insights concerning the role of endogenous opiates in the pathophysiology of hypertension. Study 3 will evaluate nociceptive responses as a means of identifying those at greatest risk for hypertension among heterogeneous groups of high risk men and women. This information could be used to identify the best candidates for behavioral and other risk reduction efforts.