ENDOGENOUS OPIOIDS, PAIN AND BLOOD PRESSURE CONTROL

这项建议是为了继续我们正在进行的关于阿片类药物异常和高血压高危人群血压反应性的研究。我们逐渐意识到，在高血压前期人群中，血压和疼痛敏感性的调节都发生了变化。例如，有高血压风险的人减少了阿片类药物对血压压力反应的抑制。矛盾的是，它们还显示出与夸大的阿片类药物功能一致的抗伤害效应。疼痛敏感性改变和血压失调之间的联系的科学意义，无论是基础还是临床，仍有待阐明。最近，我们和其他人的研究强调了阿片类药物在调节神经内分泌和血压方面的重要性：1)高血压发展中对应激的反应，2)对疼痛的行为反应，以及3)疼痛敏感性和血压之间的关系。这一继续建议的目的是通过研究高血压风险增加者的循环和行为反应，进一步研究内源性阿片类药物在血压失调中的作用。这将通过比较阿片类药物阻断和纳曲酮对临时血压轻度升高的年轻男性和女性的疼痛敏感性和血压反应性的影响来实现。我们假设在高血压发展的早期阶段血压控制和疼痛敏感性的异常与阿片肽功能的改变有关。有高血压风险的人在面对阿片类药物对血压反应性的抑制减弱时，会表现出夸大的阿片类药物对疼痛敏感性的抑制。提高对疼痛敏感性改变和血压控制的阿片基础的理解将澄清高血压的病因特征，并可能提供新的预防、诊断和治疗策略。

This proposal is for continuation of our ongoing research on opioid abnormalities and blood pressure reactivity in persons at risk for hypertension. We are gradually becoming aware that regulation of both blood pressure and pain sensitivity is altered in pre-hypertensive populations. For example, persons at risk for hypertension have decreased opioid inhibition of blood pressure responses to stress. Paradoxically, they also show antinociceptive effects consistent with exaggerated opioid function. The scientific meaningfulness, both basic and clinical, of the links between pain sensitivity alterations and blood pressure dysregulation remains to be clarified. Recent studies by ourselves and others have emphasized the importance of opioids in regulation of 1) neuroendocrine and blood pressure responses to stress in hypertension development, 2) behavioral responses to pain, and 3) the relationship between pain sensitivity and blood pressure. The purpose of this continuation proposal is to further examine the role of endogenous opioids in blood pressure dysregulation by studies of circulatory and behavioral responses to aversive stimuli in persons at enhanced risk for hypertension. This will be accomplished by comparison of the effects of opioid blockade with naltrexone on pain sensitivity and blood pressure reactivity in young men and women with mildly elevated casual blood pressure. We hypothesize that abnormalities of both blood pressure control and pain sensitivity in the early stages of hypertension development are linked to altered opioid peptide function. Persons at risk for hypertension will show exaggerated opioid inhibition of pain sensitivity in the face of diminished opioid inhibition of blood pressure reactivity. Improved understanding of the opioidergic basis of altered pain sensitivity and blood pressure control will clarify the poorly characterized etiology of essential hypertension and possibly offer new preventive, diagnostic and therapeutic strategies.