GABA/OPIOID TREATMENT OF ACUTE POSTSURGICAL PAIN

GABA/阿片类药物治疗术后急性疼痛

• 批准号: 2257941
• 负责人: JON DAVID LEVINE
• 金额: $ 22.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2257941
• 关键词: African American; Asian Americans; GABA receptor; Hispanic Americans; caucasian American; drug adverse effect; gender difference; human subject; human therapy evaluation; menstrual cycle; morphine; opiate alkaloid; pain threshold; postoperative state; prognosis; racial /ethnic difference; tooth extraction

The treatment of acute pain, with effective agents that produce only minimal side-effects, is key to the management of ambulatory surgery patients. Unfortunately, a large number of ambulatory surgeries each year are followed by hospital admission, and admission is often due to either opioid-induced side-effects or inadequate pain control. Recent attempts to avoid these difficulties have focused on combining an opioid with a non- opioid drug, usually a non-opiate analgesic, or a drug promoting action in the endogenous pain control circuits activated by administered opioids. We have been successful in producing enhanced analgesia by combining opioids of different receptor classes, or by administering a tricyclic agent or an alpha2-adrenergic agent, with an opioid. A large amount of experimental evidence from animal studies exists demonstrating that GABAergic mechanisms are involved in opioid analgesia at both spinal and supraspinal sites. Activity of the GABA(A) receptor appears to antagonize opioid analgesia, while activity at the GABA(B) receptor appears to promote opioid analgesia. In this proposal we will employ our standardized model of outpatient surgery, surgical removal of bony impacted mandibular third molars, to evaluate the effect of the combination of baclofen or flumazenil with morphine, on postoperative pain. Flumazenil, a benzodiazepine antagonist would be expected to inhibit activity at the GABA(A) receptor; baclofen is a GABA(B) agonist. We will assess analgesic efficacy of these combinations compared to administration of morphine alone. In addition, to assess the clinical usefulness of these analgesic drug combinations, we will evaluate other outcome measures, including severity of side-effects, amount of postoperative opioid administered, and patient satisfaction with the various regimens. All of these measures will be evaluated through the second postoperative day. Finally, since gender, menstrual cycle phase, and ethnicity may influence pain intensity and drug-induced side-effects, we will also evaluate, for each drug group, the effect of these factors on pain intensity and severity of side-effects. This study has the potential to develop drug combinations that offer a significantly enhanced analgesia and reduced side-effects, and greater patient comfort and satisfaction, compared to regimens currently available. In addition, since it should be possible to discharge patients earlier after ambulatory surgery and avoid post-surgery hospital admissions, clinical use of such drug combinations may result in substantial decreases in health care expenses. The study will also provide important novel information on interactions between GABAergic and opioidergic mechanisms in pain and endogenous analgesic neuronal circuitry in humans.

急性疼痛的治疗，仅产生有效药物 最小的副作用是管理手术的关键 患者。不幸的是，每年进行大量门诊手术 接下来是住院，入院通常是由于 阿片类药物引起的副作用或疼痛控制不足。最近的尝试 避免这些困难的重点是将阿片类药物与非 - 阿片类药物，通常是非生物镇痛药或促进药物的药物 由施用的阿片类药物激活的内源性疼痛控制电路。我们 通过结合阿片类药物成功产生增强的镇痛 不同的受体类别，或通过管理三环剂或 α2-肾上腺素能，含阿片类药物。 存在大量来自动物研究的实验证据 证明GABA能机制参与阿片类镇痛 在脊柱和脊柱上部。 GABA（a）受体的活性 似乎拮抗阿片类镇痛，而GABA的活性（B） 受体似乎促进阿片类镇痛。在这个建议中，我们将 采用我们的标准化门诊手术模型，手术去除 骨影响下颌第三磨牙，以评估 巴氯芬或氟马西尼与吗啡的组合，术后 疼痛。氟马兹尼，苯二氮卓类拮抗剂有望抑制 GABA（a）受体的活性； Baclofen是GABA（B）激动剂。我们将 与给药相比，评估这些组合的镇痛功效 单独使用吗啡。另外，以评估这些的临床实用性 镇痛药组合，我们将评估其他结果指标， 包括副作用的严重程度，术后阿片类药物的量 给药，并对各种方案的患者满意。所有人 这些措施将在第二天的第二天进行评估。 最后，由于性别，月经周期阶段和种族可能会影响 疼痛强度和药物引起的副作用，我们还将评估，因为 每个药物组，这些因素对疼痛强度和 副作用的严重程度。 这项研究有可能开发提供的药物组合 显着增强镇痛和副作用减少，更大 与目前的方案相比，患者的舒适和满意 可用的。另外，由于应该有可能出院 门诊手术后早些时候避免手术后医院 入院，这种药物组合的临床使用可能会导致 医疗保健费用大幅下降。该研究还将提供 有关GABA能和互动的重要新颖信息 疼痛和内源性镇痛神经元电路中的阿片类药物机制 在人类中。