Pain suppressed wheel running in the rat

摘要 慢性疼痛是一个复杂的问题，影响着全世界超过10亿人。一个重要的目标，基本 科学家们将在动物身上开发和测试治疗方法， 患者慢性疼痛患者遭受痛苦，因为疼痛和日常生活的中断 (e.g.,锻炼，社交）。恢复正常活动的治疗方法的发展将需要 使用模拟这些效应的疼痛测试。大多数临床前疼痛模型评估动物的反应 有害的刺激。这种疼痛刺激测试有助于揭示刺激是否有害， 但不能模拟疼痛对活动的破坏性影响。我们的目标是用镇压家园 大鼠在笼子里跑轮子，作为人类疼痛抑制活动的模型。车轮运行是一种自然的 啮齿动物的行为，不需要训练，除了把一个运行轮在老鼠的家笼。 尽管已经开发了许多疼痛抑制测试，包括抑制轮状神经节， 跑，家庭笼轮运行可能是一个特别有用的模型，因为轮运行是一个 自然啮齿动物行为，在大鼠的饲养笼（低压力环境）中进行评估，以及 可以一天24小时进行测量。拟议中的研究将揭示车轮运行是否是 通过测试患有炎症和偏头痛的大鼠来准确测量临床疼痛。五个具体 假设将被测试：1）炎症和偏头痛将抑制轮运行; 2） 用轮跑测量的炎性疼痛的情感维度将在伤害性疼痛之前恢复。 刺激诱发反应; 3）疼痛治疗的管理将恢复疼痛抑制轮 4）轮跑将区分抗伤害感受（增加轮跑）和 药物治疗的副作用（减少车轮运行）;和5）雌性大鼠将更敏感 比雄性老鼠更容易产生疼痛抑制的车轮运动。这些假设将通过监测轮进行检验- 在完全弗氏给药前后在雄性和雌性大鼠的饲养笼中奔跑 在右后爪中给予佐剂（CFA）以诱导炎性疼痛或给予TRPA 1激动剂 硬脑膜上引起偏头痛车轮运行将每天23小时进行评估， 7天每天将大鼠移出一次以评估疼痛诱发的行为（von Frey和Hargreaves 测试）和给药（CFA，酮洛芬，吗啡，安非他明，舒马曲坦）。这些研究 将揭示是否疼痛抑制轮运行是一个可靠的措施伤害性和有效的模型 疼痛抑制的行为。鉴于需要开发新的镇痛剂和改进 现有的临床前疼痛测定，拟议的研究可以提供一个显着的进步，疼痛 research.

Abstract Chronic pain is a complex problem affecting over a billion people worldwide. An important goal for basic scientists is to develop and test treatments in animals that can be translated for use in chronic pain patients. Chronic pain patients suffer both because of the pain and the disruption of daily life routines (e.g., exercise, socializing). The development of treatments that restore normal activity will require the use of pain tests that mimic these effects. Most preclinical models of pain assess an animal's response to a noxious stimulus. Such pain-stimulated tests are useful in revealing whether a stimulus is noxious, but do not mimic the disruptive effects of pain on activity. Our objective is to use suppression of home cage wheel running in rats as a model of pain-suppressed activity in humans. Wheel running is a natural rodent behavior that requires no training other than placing a running wheel in the rat's home cage. Although a number of pain-suppressed tests have been developed including suppression of wheel running, home cage wheel-running could be a particularly useful model because wheel-running is a natural rodent behavior, assessment takes place in the rat's home cage (a low-stress environment), and measurements can be taken 24 hours a day. The proposed studies will reveal whether wheel-running is an accurate measure of clinical pain by testing rats with inflammatory and migraine pain. Five specific hypotheses will be tested: 1) Inflammatory and migraine pain will suppress wheel-running; 2) The affective dimension of inflammatory pain measured with wheel running will recover prior to noxious stimuli evoked responses; 3) Administration of pain treatments will restore pain-suppressed wheel running; 4) Wheel-running will distinguish between the antinociceptive (increased wheel running) and side effects (decreased wheel running) of drug treatments; and 5) Female rats will be more sensitive than male rats to pain-suppressed wheel running. These hypotheses will be tested by monitoring wheel- running in the home cage of male and female rats before and after administration of Complete Freund's Adjuvant (CFA) in the right hindpaw to induce inflammatory pain or administration of a TRPA1 agonist onto the dura mater to induce migraine pain. Wheel running will be assessed 23 hours a day for at least 7 days. Rats will be removed once a day to assess pain-evoked behavior (von Frey and Hargreaves tests) and to administer drugs (CFA, ketoprofen, morphine, amphetamine, sumatriptan). These studies will reveal whether pain-suppressed wheel running is a reliable measure of nociception and a valid model of pain-suppressed behavior in humans. Given the need to develop novel analgesics and improve upon existing preclinical pain assays, the proposed studies could provide a significant advance in pain research.