Molecular signatures of endocannabinoid induced pain relief in humans: lifestyle interventions, systemic and localised changes.

内源性大麻素是我们身体产生的分子，类似于大麻中的一些物质。它们调节食欲、情绪、睡眠、肌肉力量、炎症，还与我们对疼痛的感觉和反应有关。人们一直在努力生产类似于“内源性大麻素”的新药来治疗各种疾病，但由于它们涉及的功能太多，这些化合物最终会产生无法预料的副作用。我们肠道中的微生物与人们所经历的疼痛和炎症程度有关。众所周知，体育锻炼可以减轻患有关节炎等慢性疾病的人的疼痛程度。我们希望了解（识别）所有这些与疼痛相关的过程中所涉及的分子，方法是让人们在六周内服用纤维或做运动，这两种运动都会增加内源性大麻素的水平。我们将测量疼痛水平和疼痛敏感性，人们的情绪，并采血测量内源性大麻素，肠道微生物，微生物产生的物质，改变炎症的物质，本研究的结果将在以下方面帮助慢性疼痛患者：1。了解饮食和运动等生活方式干预的机制，以及它们是否可以相互补充以改善疼痛。测量内源性大麻素的变化对减轻疼痛的影响与情绪的变化、炎症的变化或与疼痛传递直接相关的物质的不同水平有多大的关系，以及我们体内的哪些基因参与其中。了解是否有分子因素可以改善或减少内源性大麻素的变化及其对疼痛的影响。通过了解针对内源性大麻素系统的各种药物受体调节的机制，帮助开发治疗疼痛的新药

Endocannabinoids are molecules made by our bodies which are similar to some of the substances in marijuana. They regulate appetite, mood, sleep, muscle strength, inflammation and they also are involved in how strongly we feel and respond to pain. There have been efforts to generate new drugs that are similar to "endocannabinoids" to treat various diseases but because they are involved in so many functions these compounds end up having unforeseen side effects. The microbes in our guts have been implicated in the levels of pain and inflammation that people experience. And physical exercises are well known to reduce the levels of pain experienced by people with chronic conditions such as arthritis. We propose to understand (identify) the molecules that are involved in all of these related processes linked to pain by asking people to take fibre and or do exercise for six weeks, both of which increase endocannabinoid levels We will measure levels of pain and pain sensitivity, peoples' mood, and take bloods to measure endocannabinoids, gut microbes, substances produced by microbes that alter inflammation, inflammatory substances, other pain related substances The results of this study will help people with chronic pain in the following ways:1. Understand the mechanisms by which lifestyle interventions like diet and exercise work and whether they can be added to each other to improve pain.2. To measure how much of the effects of changes in endocannabinoids on pain reduction is linked to changes in mood or to changes in inflammation or to different levels of substances directly related to pain transmission and which genes in our bodies are involved3. Understand if there are molecular factors that result in improved or reduced endocannabinoid changes and their effects on pain4. Help develop new drugs to treat pain by understanding which mechanisms are modulated by the various receptors of drugs that target the endocannabinoid system