Impact of advanced age on opiate analgesia

摘要 这些研究的目的是了解老年对阿片类药物调节的影响。 持续的疼痛。2013年，65岁及以上人口占美国总人口的14.1%。这些 预计这一数字将大幅上升，65岁或以上的人占20- 到2030年占总人口的30%。不幸的是，寿命延长的后果之一 是疼痛，65岁或以上的人口中有45%-85%的人每天都会经历疼痛。 不幸的是，大多数老年人的慢性疼痛没有得到充分的治疗。一个主要因素 疼痛管理不足的原因之一是缺乏对年龄影响的了解 对疼痛和鸦片类药物敏感。事实上，一个多学科组织最近发表的一份共识声明 疼痛专家小组指出：“老年人阿片类药物使用指南的缺乏反映了这一点。 这些药物在老年人身上的研究。清楚地了解与年龄相关的变化 男性和女性的阿片能环路对于循证疼痛管理至关重要。 人口。我们的行为学数据表明，吗啡的止痛作用显著。 老年(18-24个月)大鼠与成年(2-3个月)大鼠相比减弱。事实上，ED50为老年人提供了剂量 动物摄入量为7.0毫克/公斤，成人为3.5毫克/公斤。我们最重要的假设是年龄- Mu阿片受体在中脑内表达和信号的诱导变化 中脑导水管周围灰质(PAG)是阿片类药物敏感性降低的生物学基础 在老年人中观察到。提出了三个具体目标来确定先进的 年龄对MU阿片受体表达及受体药效学(SA1)和G蛋白的影响 受体偶联与调节(SA2)。目标3将使用分子和药理学技术 以增强中枢MOR信号，从而减少吗啡剂量需求。加在一起，这些 研究将提供关于年龄对阿片剂有效性影响的新的和关键的数据，并将 鼓励以证据为基础的治疗方法来管理老年人的疼痛。

ABSTRACT The goal of these studies is to understand the impact of advanced age on opiate modulation of persistent pain. In 2013, people aged 65 and older represented 14.1% of the US population. These numbers are expected to rise dramatically, with person’s aged 65 years or older accounting for 20- 30% of the total population by 2030. Unfortunately, one of the consequences of increased longevity is pain, with 45-85% of the population aged 65 or older experiencing pain on a daily basis. Unfortunately, chronic pain is under-treated for the majority of elderly persons. A primary factor contributing to the under management of pain is the dearth of knowledge on the impact of age on pain and opiate sensitivity. Indeed, a recent consensus statement issued by a multidisciplinary group of pain experts states: “The paucity of guidelines for opioid use in the elderly reflects the lack of studies of these drugs on the old.” A clear understanding of age-associated changes in opioidergic circuits of males and females is critical for evidence-based pain management in this population. Our behavioral data indicate that the antihyperalgesic effect of morphine is significantly attenuated in aged (18-24 mos) versus adult (2-3 mos) rats. Indeed, the ED50 dose for aged animals is 7.0 mg/kg in comparison to 3.5 mg/kg for adults. Our overarching hypothesis is that age- induced changes in mu opioid receptor expression and signaling within the midbrain periaqueductal gray (PAG) provide the biological bases for the decreased sensitivity to opiates observed in the elderly. Three specific aims are proposed to determine the influence of advanced age on mu opioid receptor expression and receptor pharmacodynamics (SA1) and G protein receptor coupling and regulation (SA2). Aim 3 will use molecular and pharmacological techniques to boost central MOR signaling, thereby reducing morphine dosing requirements. Together, these studies will provide novel and critical data on the impact of age on opiate effectiveness, and will stimulate evidence-based therapies for the management of pain in the elderly.