HYPERTENSION, RISK FOR HYPERTENSION AND HYPOALGESIA

拟议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。该研究将验证痛觉减退和高血压具有共同的病理生理（即中枢阿片类药物低敏感性）的假设，其特征是内源性阿片类药物和脊柱上疼痛调节系统的激活增强。在这种假设是正确的情况下，休息时、阿片类药物阻断期间和棘上激活期间伤害性反应的个体差异可能用于预测血压的纵向变化。这个项目的发现也可能有助于解释临床疼痛（如心绞痛）的减轻，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）作为伤害性的客观测量，NFR定义为引起腿部退缩所需的腓肠神经刺激强度。研究1将确定新诊断高血压的对照组和未用药患者的NFR阈值，并将评估内源性阿片类药物和降痛调节作为高血压痛觉减退的介质。研究2将确定高血压高风险和低风险年轻人的NFR阈值（由父母高血压史和静息血压定义），并将评估内源性阿片类药物和降痛调节作为高血压高风险人群痛觉减少的介质。研究3将评估静息时NFR阈值和NFR阈值在椎管上调节下的变化，作为高血压高风险和低风险年轻人血压纵向变化的预测因子。提出的研究之所以重要，有几个原因。研究1和2将评估痛觉减退的有希望的机制，这可能会导致关于内源性阿片类药物在高血压病理生理中的作用的重要见解。研究3将评估伤害性反应，作为在不同类型的高血压高危人群中识别高血压高危人群的手段。这些信息可以用来确定行为和其他减少风险努力的最佳候选人。

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.