Choline treatment for inflammatory pain

胆碱治疗炎性疼痛

• 批准号: 8327488
• 负责人: PAMELA Dru FLOOD
• 金额: $ 16.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2012-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8327488
• 关键词: Acute inflammatory pain; Affect; Aftercare; American; Analgesics; Animal Model; Animals; Blood specimen; Brain; Breakthrough Pain; Cells; Choline; Clinical Research; Data; Dose; Double-Blind Method; Drug Kinetics; Food; Gelatin; Genotype; Gynecologic Surgical Procedures; Heterogeneity; Hour; Human; Human Volunteers; In Vitro; Individual; Inflammatory; Infusion procedures; Intake; Lecithin; Link; Marketing; Measures; Mediating; Memory; Modeling; Morphine; Nausea and Vomiting; Neurons; Nicotinic Receptors; Nutritional; Operative Surgical Procedures; Opioid; Pain; Pathway interactions; Patient Self-Report; Patient-Controlled Analgesia; Patients; Perioperative; Pharmaceutical Preparations; Pharmacodynamics; Pilot Projects; Placebo Control; Plasma; Postoperative Pain; Postoperative Period; Property; Pruritus; Public Health; Randomized; Regimen; Regression Analysis; Reporting; Sedation procedure; Supplementation; Surgical wound; Variant; allodynia; analog; dietary supplements; experience; inflammatory pain; macrophage; mouse model; nervous system disorder; patient population; primary outcome; public health relevance; receptor; receptor expression; response; satisfaction; secondary outcome; subcutaneous

DESCRIPTION (provided by applicant): Pain is a major public health issue that affects 1 in 5 Americans. After surgery, 70-80% of patients experience moderate to severe pain despite "state of the art" treatment with opioids and other drugs. Lecithin and phosphatidylcholine are nutritional supplements that are widely marketed to increase choline intake in humans. There is considerable evidence from animal models that choline supplementation has pain-relieving properties and can reduce inflammatory and postoperative pain. Choline is thought to have analgesic properties in animals by activating a7 nicotinic acetylcholine receptors in neurons and/or inflammatory cells. We propose a pilot clinical study to determine whether supplementation with lecithin and phosphatidylcholine to increase plasma choline concentrations before gynecological surgery will decrease post-operative pain. We will conduct a linked pharmacokinetic/ pharmacodynamic trial with the primary outcome variable of reported pain score after surgery. In this placebo-controlled double-blind study all patients will receive the optimal postoperative pain regimen with morphine via PCA. We will assess whether choline supplementation affects patients' use of pain medication and satisfaction with pain relief. Furthermore, we will conduct an exploratory analysis of subject macrophages for a7 receptor expression level and activity in subject macrophages. We will determine whether heterogeneity in a7 nicotinic receptors is predictive of intra-individual variation in choline efficacy. PUBLIC HEALTH RELEVANCE: This is a pilot pharmacokinetic/pharmacodynamic study to determine whether nutritional supplementation with lecithin increases plasma choline concentration and decreases pain after surgery. In an exploratory analysis we will determine whether supplementation reduces the activity of subject macrophages through an alpha 7 nicotinic receptor dependent pathway.

描述（由申请人提供）：疼痛是影响五分之一美国人的主要公共卫生问题。手术后，尽管使用阿片类药物和其他药物进行“最先进”的治疗，70-80% 的患者仍会经历中度至重度疼痛。卵磷脂和磷脂酰胆碱是广泛销售的营养补充剂，可增加人类胆碱的摄入量。来自动物模型的大量证据表明，补充胆碱具有缓解疼痛的特性，可以减轻炎症和术后疼痛。胆碱被认为通过激活神经元和/或炎症细胞中的 a7 烟碱乙酰胆碱受体而在动物中具有镇痛作用。我们提出了一项试点临床研究，以确定在妇科手术前补充卵磷脂和磷脂酰胆碱以增加血浆胆碱浓度是否会减少术后疼痛。我们将进行一项关联的药代动力学/药效学试验，主要结果变量是术后报告的疼痛评分。在这项安慰剂对照双盲研究中，所有患者都将通过 PCA 接受吗啡的最佳术后疼痛方案。我们将评估补充胆碱是否影响患者对止痛药的使用以及对疼痛缓解的满意度。此外，我们将对受试者巨噬细胞的α7受体表达水平和活性进行探索性分析。我们将确定 a7 烟碱受体的异质性是否可以预测胆碱功效的个体内差异。 公众健康相关性：这是一项药代动力学/药效学试验研究，旨在确定补充卵磷脂营养是否会增加血浆胆碱浓度并减轻手术后的疼痛。在探索性分析中，我们将确定补充剂是否通过 α7 烟碱受体依赖性途径降低受试者巨噬细胞的活性。

项目成果

Oral choline supplementation for postoperative pain.

口服胆碱补充剂可缓解术后疼痛。

• DOI: 10.1093/bja/aet031
• 发表时间: 2013
• 期刊: British journal of anaesthesia
• 影响因子: 9.8
• 作者: Sidhu,N;Davies,S;Nadarajah,A;Rivera,J;Whittington,R;Mercier,RJ;Virag,L;Wang,S;Flood,P
• 通讯作者: Flood,P

Nicotine nasal spray as an adjuvant analgesic for third molar surgery.

尼古丁鼻喷雾剂作为第三磨牙手术的辅助镇痛剂。

• DOI: 10.1016/j.joms.2010.07.025
• 发表时间: 2011
• 期刊: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons
• 作者: Yagoubian,Benjamin;Akkara,Joseph;Afzali,Payam;Alfi,DavidM;Olson,Luke;Conell-Price,Jessamyn;Yeh,Janet;Eisig,SidneyB;Flood,Pamela
• 通讯作者: Flood,Pamela