The Effects of Ketogenic Diets on Inflammation and Chronic Pain

生酮饮食对炎症和慢性疼痛的影响

• 批准号: 7981181
• 负责人: David Nathaniel Ruskin
• 金额: $ 22.36万
• 依托单位: TRINITY COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981181
• 关键词: Absence of pain sensation; Acute; Address; Adenosine; Adverse effects; Analgesics; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Anticonvulsants; Arthritis; Atkins Diet; Basic Science; Biochemical; Blood; Caloric Restriction; Carbohydrates; Childhood; Chronic; Chronic Brain Injury; Clinical; Development; Diabetes Mellitus; Diet; Disease; Epilepsy; Extravasation; Fatty acid glycerol esters; Freund' s Adjuvant; Goals; Healthcare Industry; Heating; Human; Hydroxybutyrates; Hyperalgesia; Inflammation; Inflammatory; Injection of therapeutic agent; Intractable Epilepsy; Intractable Pain; Ketones; Ketoses; Ketosis; Lead; Measures; Metabolism; Nature; Neuromodulator; Neurons; Neuropathy; Nociception; Opiates; Opioid; Pain; Pain Threshold; Pain management; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Physiological; Plasma; Proteins; Reactive Oxygen Species; Refractory; Regimen; Rheumatoid Arthritis; Swelling; Tactile; Tactile Hyperalgesias; Testing; Therapeutic; Tissues; Work; allodynia; base; behavior measurement; chronic pain; clinical efficacy; cost; effective therapy; glucose metabolism; inflammatory neuropathic pain; inflammatory pain; ketogenesis; ketogenic diet; ketogentic; nerve injury; neuroprotection; novel; novel therapeutics; painful neuropathy; palliative; prevent; public health relevance; relating to nervous system; research study; sciatic nerve; subcutaneous; success; tool

DESCRIPTION (provided by applicant): A great unmet need exists for pain therapies that are non-addictive and/or address pain that remains intractable to treatments available currently. Opiates, the most powerful drugs to treat pain, pose serious side effects and addictive potential and are sometimes ineffective. Two major non-opioid strategies to address pain are focused on either reducing inflammation and inflammatory pain (particularly relevant to arthritis) or reducing neural activity and neuropathic pain (particularly relevant to diabetes and nerve injury). There is emerging evidence to suggest that a ketogenic diet may alleviate pain. A ketogenic diet is a regimen that it is high in fat and low in carbohydrates, similar to the Atkins diet. The carbohydrate restriction decreases the metabolism of glucose and increases the metabolism of ketones. To date, the ketogenic diet has shown proven clinical efficacy in epilepsy and demonstrated basic research potential for neuroprotection in several types of acute and chronic brain injuries. A number of biochemical consequences of a ketogenic diet - decreased reactive oxygen species, decreased neural activity, increased adenosine and activation of peroxisome proliferator-activated receptors - all suggest that a ketogenic diet will be effective in increasing baseline pain thresholds and reducing both inflammatory and neuropathic pain. Our central hypothesis is that a ketogenic diet will alleviate pain, including intractable pain, based on its anti-inflammatory potential and akin to its success in treating intractable epilepsy. Despite multiple lines of evidence supporting our central hypothesis, the efficacy of a ketogenic diet in treating pain has not been tested either clinically or in animal models. The present objective is to test the effects of a ketogenic diet on baseline pain thresholds, inflammatory pain (Specific Aim 1) and neuropathic pain (Specific Aim 2). Testing our hypothesis in well-established animal models is feasible and may yield new therapeutic opportunities for pain relief and a new avenue for developing pain treatments that are both effective and non-addictive. PUBLIC HEALTH RELEVANCE: Chronic pain is a common and debilitating condition, strikingly reducing the costing the health care industry tens of billions of dollars annually. Evidence suggests that a ketogenic (very low carbohydrate/high fat) diet should provide relief in two types of chronic pain, inflammatory and neuropathic pain, found most commonly in rheumatoid arthritis and diabetes, respectively. This proposal will quantify the preventative and palliative effects of two ketogenic diets in well-characterized animal models of inflammatory and neuropathic pain.

描述（由申请人提供）：对疼痛疗法的巨大需求是无依化的和/或解决疼痛的疼痛，这对于目前可用的治疗仍然很棘手。阿片类药物是治疗疼痛，造成严重副作用和上瘾潜力的最强大药物，有时是无效的。解决疼痛的两种主要非阿片类药物策略集中在减轻炎症和炎症性疼痛（尤其与关节炎有关）或减少神经活动和神经性疼痛（尤其与糖尿病和神经损伤有关）。 有新兴的证据表明，生酮饮食可以减轻疼痛。生酮饮食是一种与阿特金斯饮食相似的脂肪含量高且碳水化合物低的方案。碳水化合物限制会降低葡萄糖的代谢，并增加酮的代谢。迄今为止，生酮饮食已经在癫痫病中证明了临床疗效，并在几种类型的急性和慢性脑损伤中证明了基础研究潜力。生酮饮食的许多生化后果 - 减少活性氧，神经活性降低，腺苷增加和过氧化物酶体增殖物激活受体的激活 - 所有的酮饮食都表明，生酮饮食将有效地增加基线止痛阈值，并减少炎症性和神经性疼痛。 我们的中心假设是，生酮饮食会根据其抗炎潜力缓解疼痛，包括棘手的疼痛，并且类似于其在治疗顽固性癫痫中的成功。尽管有多种证据支持我们的中心假设，但生酮饮食在治疗疼痛方面的功效尚未在临床上或动物模型中进行测试。目前的目标是测试生酮饮食对基线疼痛阈值，炎症性疼痛（特定目标1）和神经性疼痛（特定目标2）的影响。检验我们在建立良好的动物模型中的假设是可行的，可能会为缓解疼痛而产生新的治疗机会，并为开发既有效且不依赖的疼痛治疗的新途径。 公共卫生相关性：慢性疼痛是一种常见且令人衰弱的状况，大大降低了每年数千亿美元的卫生保健行业的成本。有证据表明，生酮（非常低的碳水化合物/高脂肪）饮食应分别以两种类型的慢性疼痛，炎性和神经性疼痛来缓解，分别在类风湿关节炎和糖尿病中发现。该提案将量化两种生酮饮食在炎症和神经性疼痛的良好特征动物模型中的预防和姑息性作用。