Effects of Light at Night and Disrupted Circadian Rhythms on Pain

夜间光线和昼夜节律紊乱对疼痛的影响

• 批准号: 10301363
• 负责人: Randy J. Nelson
• 金额: $ 19万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-15 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10301363
• 关键词: Adoption; Affect; Animal Experimentation; Animals; Antibodies; Behavior; Behavioral; Circadian Dysregulation; Circadian Rhythms; Clinical; Data; Disease; Dose; Exposure to; Female; Genes; Goals; Goggles; Home; Hour; Human; IL6 gene; Individual; Industrialization; Inflammation; Inflammatory; Knowledge; Lead; Life; Light; Lighting; Mediating; Medical Care Costs; Modernization; Mus; Nociception; Opiate Addiction; Opioid; Pain; Pain management; Pathway interactions; Peptides; Peripheral; Persons; Physiology; Pollution; Predictive Factor; Prevalence; Process; Productivity; Retinal Ganglion Cells; Role; Schedule; Sex Differences; Stimulus; System; Testing; Therapeutic Uses; Translating; Treatment outcome; Variant; central pain; chronic pain management; circadian; circadian pacemaker; dosage; endogenous opioids; epidemiologic data; experience; improved; individual variation; light effects; male; melanopsin; opioid abuse; opioid use; optimal treatments; peripheral pain; prevent; response

Abstract Widespread adoption of electric lighting has led to significant exposure to artificial light at night (LAN). Although initially assumed innocuous, exposure to LAN disrupts circadian rhythms and is correlated with increased prevalence of several clinical disorders. This so-called light pollution began prior to a deep appreciation of the importance of circadian rhythms to typical, adaptive functioning. Our preliminary data indicate that exposure to LAN disrupts circadian rhythms, dramatically increases peripheral and central inflammation, and elevates pain responsiveness in mice. Pain is a significant cause of high medical costs, lost productivity, and a common pathway to opiate addiction. Currently, there are few optimal treatments for chronic pain and the underlying causes, and predictive factors that lead individuals from therapeutic use to opiate abuse remain unspecified. Pain responsiveness shows daily variation with elevated responses at night. We hypothesize that disrupted circadian rhythms, caused by exposure to LAN, drive inflammatory processes and influence pain responsiveness. We will test this hypothesis and predict that mice exposed to dim light at night (dLAN) will display elevated pain responsiveness. We further hypothesize that circadian responses to opiate management of pain are deranged by light at night. Thus, we predict that higher doses of opiates are required to obtain similar suppression of pain responses in animals exposed to dim light at night. These hypotheses will be tested in two specific aims. In the first specific aim, we will characterize the effects of dLAN exposure on pain responsiveness in mice. Because of the well-known sex differences in pain responsiveness, we will test both male and female mice in pain responsiveness after exposure to dLAN. Circadian clocks are entrained by light interacting with melanopsin-expressing retinal ganglion cells which are primarily responsive to short-wavelength (blue) light, and relatively unresponsive to long wavelength (red) light. Thus, we will examine pain responsiveness after exposure to dark, dim white, dim blue, or dim red light at night to test the hypothesis that exposure to dLAN comprised of wavelengths that affect circadian clock entrainment (white and blue) will elevate pain responsiveness, whereas exposure to dark nights or dim red light at night prevents elevated pain responsiveness. Specific Aim 2 will test the hypothesis that disruption of circadian organization by exposure to dLAN changes sensitivity/ responsiveness to opiates. We predict that dose responses to opiates will shift so that increased opiate dosages will be required to suppress pain responses. Taken together, the results of this project will fill an important gap in knowledge about the role of circadian rhythms in pain responses and pain treatment. If our hypotheses are not disproved, then these results could easily and inexpensively be translated to individuals suffering from pain—e.g., blue-light blocking goggles or other environmental lighting adjustments—to align circadian rhythms, to improve pain treatment outcomes, and avoid opiate abuse.

抽象的 电灯的广泛采用导致夜间（LAN）大量暴露于人造照明。 尽管最初是无害的，但暴露于LAN会破坏昼夜节律，并与 增加了几种临床疾病的患病率。这种所谓的光污染开始于深处 欣赏昼夜节律对典型的自适应功能的重要性。我们的初步数据 表明暴露于LAN会破坏昼夜节律，大大增加外围和中央 炎症，并提高小鼠的疼痛反应能力。疼痛是造成高医疗费用的重要原因， 失去生产力，也是优化成瘾的常见途径。目前，很少有最佳治疗方法 慢性疼痛和根本原因，以及导致个人治疗使用的预测因素 滥用行动仍然未指定。疼痛反应能力显示每日变化，反应升高 夜晚。我们假设由暴露于LAN引起的昼夜节律破坏了，驱动炎症 过程并影响疼痛的反应能力。我们将检验这一假设，并预测暴露于 晚上（DLAN）昏暗的光将显示出较高的疼痛反应能力。我们进一步假设昼夜节律 晚上光线会使对疼痛的治疗进行优化的响应。这，我们预测较高的剂量 需要优化器的抑制作用类似，以抑制暴露于昏暗光的动物中的疼痛反应 夜晚。这些假设将以两个具体的目的进行检验。在第一个特定目标中，我们将表征 DLAN暴露对小鼠疼痛反应性的影响。由于众所周知的性别差异 疼痛反应能力，我们将在暴露后测试男性和雌性小鼠的疼痛反应能力 Dlan。昼夜节律时钟与表达黑素神经节细胞的光相互作用。 对短波长（蓝色）光的主要响应，并且对长期不反应 波长（红色）光。那就是，我们将检查暴露于黑暗，昏暗，昏暗的疼痛反应能力 夜间蓝色或昏暗的红灯，以测试暴露于DLAN完成波长的假设 影响昼夜节律的入围（白色和蓝色）将提高疼痛反应能力，而暴露于 黑夜或夜间昏暗的红灯可防止疼痛升高的反应能力。具体目标2将测试 假设通过暴露于DLAN会改变敏感性/ 优化的响应能力。我们预测剂量反应以优化会发生变化，从而增加优化 需要剂量来抑制疼痛反应。综上所述，该项目的结果将填补 了解昼夜节律在疼痛反应和疼痛治疗中的作用的重要差距。如果我们 假设没有被驳回，那么这些结果很容易廉价地转化为个体 遭受痛苦 - 例如，蓝光挡块护目镜或其他环境照明调整 - 以对齐 昼夜节律，以改善疼痛治疗结果，避免滥用手术。