Endocannabinoids and Reproductive Pain

内源性大麻素和生殖疼痛

• 批准号: 6949950
• 负责人: Heather Bryte Bradshaw
• 金额: $ 5.15万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-22 至 2006-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949950
• 关键词: amidohydrolases; anandamide; arachidonate; behavior test; cannabinoid receptor; chronic pain; estrus; glycerides; glycine; hormone regulation /control mechanism; laboratory rat; liquid chromatography mass spectrometry; muscle contraction; postdoctoral investigator; uterus

DESCRIPTION (provided by applicant): The relationship between chronic pelvic pain, uterine contractility, and the chemical messengers that regulate uterine contractions and pain are not well understood. This research proposal is designed to test the hypothesis that the endocannabinoids, arachidonoylethanolamide (anandamide; AEA), 2-arachidonoyl glycerol (2-AG) and the putative lipid mediator N-arachidonoylglycine (NAGly) play a functional role in uterine contractions and pain and that this regulation is controlled by the hormonal milieu. Specific aim 1 is designed to measure endogenous levels of AEA, 2-AG, and NAGly, changes in cannabinoid receptor density and affinity, and FAAH activity in the rat reproductive tract as a function of changes in the hormonal milieu. Specific aim 2 is designed to measure the effect of AEA, 2-AG, and NAGly on uterine contraction rates and amplitudes. Specific aim 3 is designed to measure the effects of AEA, 2-AG, and NAGly on behavioral responses to noxious uterine stimulation. Preliminary data in this proposal demonstrates that uterine levels of AEA, 2-AG, and NAGly are regulated by the hormonal milieu and that this change may facilitate changes in uterine contractions. The experiments in this proposal will provide information that could lead to a novel platform from which to launch new studies in the etiology and treatment of chronic pelvic pain in women.

描述（由申请人提供）： 慢性盆腔疼痛、子宫收缩力和调节子宫收缩和疼痛的化学信使之间的关系还不清楚。这项研究计划旨在验证内源性大麻素、花生四烯酸乙醇酰胺（anandamide; AEA）、2-花生四烯酸甘油（2-AG）和假定的脂质介质N-花生四烯酸甘氨酸（NAGly）在子宫收缩和疼痛中发挥功能作用，并且这种调节受激素环境控制的假设。具体目标1旨在测量AEA、2-AG和NAGly的内源性水平，大麻素受体密度和亲和力的变化，以及大鼠生殖道中FAAH活性作为激素环境变化的函数。具体目标2被设计为测量AEA、2-AG和NAGly对子宫收缩速率和幅度的影响。具体目标3旨在测量AEA、2-AG和NAGly对有害性子宫刺激的行为反应的影响。本提案中的初步数据表明，子宫内AEA、2-AG和NAGly的水平受激素环境的调节，并且这种变化可能促进子宫收缩的变化。该提案中的实验将提供信息，可能导致一个新的平台，从该平台启动女性慢性盆腔疼痛病因学和治疗的新研究。

项目成果

Microsomal omega-hydroxylated metabolites of N-arachidonoyl dopamine are active at recombinant human TRPV1 receptors.

N-花生四烯酰多巴胺的微粒体 omega-羟基化代谢物对重组人 TRPV1 受体具有活性。

• DOI: 10.1016/j.prostaglandins.2008.08.004
• 发表时间: 2009
• 期刊: Prostaglandins & other lipid mediators
• 影响因子: 2.9
• 作者: Rimmerman,N;Bradshaw,HB;Basnet,A;Tan,B;Widlanski,TheodoreS;Walker,JM
• 通讯作者: Walker,JM

CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats.

CB1 受体阻断可减少大鼠的焦虑样反应并改善与酒精戒断相关的神经化学失衡。

• DOI: 10.1016/j.neuropharm.2008.02.005
• 发表时间: 2008
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Rubio,Marina;Fernández-Ruiz,Javier;deMiguel,Rosario;Maestro,Begoña;MichaelWalker,J;Ramos,JoséA
• 通讯作者: Ramos,JoséA

Targeted lipidomics approach for endogenous N-acyl amino acids in rat brain tissue.

• DOI: 10.1016/j.jchromb.2009.01.002
• 发表时间: 2009-09
• 期刊: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
• 作者: B. Tan;Y. W. Yu;M. F. Monn;H. Hughes;David K. O’Dell;J. Walker

Effects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain.

• DOI: 10.1152/jn.00498.2006
• 发表时间: 2006-12
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Cheng Liu;J. Michael Walker