Abstract

The humoral mediators of acute inflammation can be divided into those that activate nociceptive afferents and produce pain (e.g., bradykinin), and those that sensitize, but do not activate nociceptors and produce hyperalgesia (e.g., E-type prostaglandins). However, the poor correlation between the concentration of inflammatory mediators and intensity of symptoms in certain pathological conditions (e.g., rheumatoid arthritis) and the failure of the aspirin-like drugs to consistently produce analgesia for the pain and hyperalgesia associated with inflammation suggest that other mediators are involved in producing these symptoms. We propose to study the contribution of leukotrienes, a newly discovered class of arachidonic acid metabolites, whose synthesis is not inhibited by aspirin-like drugs, to the pain and hyperalgesia associated with inflammation with a view toward improving symptom management in humans. In preliminary experiments we have already found evidence for a receptor-mediated hyperalgesic effect of leukotriene-B4.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021647-02
Application #
3402984
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Chen, Xiaojie; Alessandri-Haber, Nicole; Levine, Jon D (2007) Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice. Mol Pain 3:31
Chen, Xiaojie; Levine, Jon D (2007) Mechanically-evoked C-fiber activity in painful alcohol and AIDS therapy neuropathy in the rat. Mol Pain 3:5
Chen, Xiaojie; Levine, Jon D (2005) Epinephrine-induced excitation and sensitization of rat C-fiber nociceptors. J Pain 6:439-46
Tanner, K D; Reichling, D B; Gear, R W et al. (2003) Altered temporal pattern of evoked afferent activity in a rat model of vincristine-induced painful peripheral neuropathy. Neuroscience 118:809-17
Joseph, E K; Levine, J D (2003) Sexual dimorphism in the contribution of protein kinase C isoforms to nociception in the streptozotocin diabetic rat. Neuroscience 120:907-13
Parada, C A; Yeh, J J; Reichling, D B et al. (2003) Transient attenuation of protein kinase Cepsilon can terminate a chronic hyperalgesic state in the rat. Neuroscience 120:219-26
Chen, X; Levine, J D (2003) Altered temporal pattern of mechanically evoked C-fiber activity in a model of diabetic neuropathy in the rat. Neuroscience 121:1007-15
Shin, Jieun; Cho, Hawon; Hwang, Sun Wook et al. (2002) Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia. Proc Natl Acad Sci U S A 99:10150-5
Dina, O A; Aley, K O; Isenberg, W et al. (2001) Sex hormones regulate the contribution of PKCepsilon and PKA signalling in inflammatory pain in the rat. Eur J Neurosci 13:2227-33
Aley, K O; Martin, A; McMahon, T et al. (2001) Nociceptor sensitization by extracellular signal-regulated kinases. J Neurosci 21:6933-9

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