Pain suppressed wheel running in the rat

摘要 慢性疼痛是一个复杂的问题，影响着全球超过10亿人。Basic的一个重要目标 科学家们将在动物身上开发和测试治疗方法，这种治疗方法可以转化为治疗慢性疼痛 病人。慢性疼痛患者的痛苦既是因为疼痛，也是因为日常生活中断 (例如，锻炼、社交)。恢复正常活动的治疗方法的开发将需要 使用模拟这些影响的疼痛测试。大多数临床前疼痛模型评估动物的反应 一种有害的刺激。这种刺激疼痛的测试有助于揭示刺激是否有害， 但不要模仿疼痛对活动的破坏性影响。我们的目标是用压制家园 大鼠笼轮运动作为人类疼痛抑制活动的模型。车轮转动是一种自然现象 啮齿动物的行为，除了在老鼠的笼子里放一个跑轮外，不需要任何训练。 虽然已经开发了许多抑制疼痛的测试，包括抑制车轮 跑步，家庭笼式车轮跑步可能是一种特别有用的模式，因为车轮跑步是一种 自然啮齿动物行为，评估在老鼠的家庭笼子(低压力环境)中进行，以及 测量可以一天24小时进行。拟议中的研究将揭示车轮行驶是否 通过测试炎症性和偏头痛大鼠的疼痛来准确测量临床疼痛。五个具体 假设将被检验：1)炎症和偏头痛疼痛会抑制车轮运行；2) 通过车轮运行测量的炎症性疼痛的情感维度将在有害的之前恢复 刺激诱发的反应；3)给予疼痛治疗将恢复疼痛抑制的车轮 跑步；4)车轮跑步将区分抗伤害作用(增加车轮跑动)和 药物治疗的副作用(减少车轮运行)；以及5)雌性大鼠将更加敏感 比雄性大鼠以疼痛抑制的轮子跑。这些假设将通过监测车轮来检验- 在完全弗氏给药前后在雌雄大鼠的家笼中奔跑 右后掌注射佐剂(CFA)以引起炎性疼痛或给予TRPA1激动剂 在硬脑膜上引起偏头痛。轮子运行将被评估为每天23小时，至少持续 7天。老鼠将每天被移走一次以评估疼痛诱发的行为(冯·弗雷和哈格里夫斯 以及管理药物(CFA、酮洛芬、吗啡、苯丙胺、舒马曲坦)。这些研究 将揭示抑制疼痛的车轮运行是否是一种可靠的伤害性测量和有效的模型 在人类中抑制疼痛的行为。鉴于需要开发新的止痛药并改进 现有的临床前疼痛分析，拟议的研究可能会在疼痛方面取得重大进展 研究。

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.