Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DA016825-01
Application #
6691102
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2003-09-22
Project End
2006-09-21
Budget Start
2003-09-22
Budget End
2004-09-21
Support Year
1
Fiscal Year
2003
Total Cost
$45,148
Indirect Cost

  Institution

Name
Brown University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912

  Publications

Tan, Bo; O'Dell, David K; Yu, Y William et al. (2010) Identification of endogenous acyl amino acids based on a targeted lipidomics approach. J Lipid Res 51:112-9
Tan, Bo; Yu, Y William; Monn, M Francesca et al. (2009) Targeted lipidomics approach for endogenous N-acyl amino acids in rat brain tissue. J Chromatogr B Analyt Technol Biomed Life Sci 877:2890-4
Rimmerman, N; Bradshaw, H B; Basnet, A et al. (2009) Microsomal omega-hydroxylated metabolites of N-arachidonoyl dopamine are active at recombinant human TRPV1 receptors. Prostaglandins Other Lipid Mediat 88:10-7
Oh, Da Young; Yoon, Jung Min; Moon, Mi Jin et al. (2008) Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. J Biol Chem 283:21054-64
Rubio, Marina; Fernandez-Ruiz, Javier; de Miguel, Rosario et al. (2008) CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology 54:976-88
Hu, S Shu-Jung; Bradshaw, H B; Chen, J S-C et al. (2008) Prostaglandin E2 glycerol ester, an endogenous COX-2 metabolite of 2-arachidonoylglycerol, induces hyperalgesia and modulates NFkappaB activity. Br J Pharmacol 153:1538-49
Rimmerman, Neta; Bradshaw, Heather B; Hughes, H Velocity et al. (2008) N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neurons. Mol Pharmacol 74:213-24
Rimmerman, N; Hughes, H V; Bradshaw, H B et al. (2008) Compartmentalization of endocannabinoids into lipid rafts in a dorsal root ganglion cell line. Br J Pharmacol 153:380-9
Rubio, Marina; McHugh, Douglas; Fernandez-Ruiz, Javier et al. (2007) Short-term exposure to alcohol in rats affects brain levels of anandamide, other N-acylethanolamines and 2-arachidonoyl-glycerol. Neurosci Lett 421:270-4
Tan, Bo; Bradshaw, Heather B; Rimmerman, Neta et al. (2006) Targeted lipidomics: discovery of new fatty acyl amides. AAPS J 8:E461-5

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