Many compounds that are produced in inflamed tissue have been identified, and certain of them are known to excite pain sensory endings. The long-term objective of this project is to determine the mechanisms by which these inflammatory mediators excite sensory endings, and thereby to identify mechanisms that might be targeted by drugs to control pain. The compound of most immediate interest in this project is bradykinin, an inflammatory peptide that can excite sensory endings at concentrations as low as 100 pM. Excitation by bradykinin will be investigated in a cell culture preparation of sensory neurons that respond in the same way as pain sensory endings in vivo. Ionic currents that produce the excitation will be identified in voltage clamp experiments, using the whole-cell patch lamp technique. Second messenger compounds that are known to be released during the response to bradykinin will also be screened for their effects on these excitatory ionic currents. To clarify how bradykinin participates in inflammatory pain, further electro-physiological experiments will examine sensory adaptation to bradykinin, and the ability of bradykinin to increase neuronal responses to other excitatory stimuli.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS025078-02
Application #
3476977
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Nardone, J; Hogan, P G (1994) Delineation of a region in the B2 bradykinin receptor that is essential for high-affinity agonist binding. Proc Natl Acad Sci U S A 91:4417-21
Nardone, J; Gerald, C; Rimawi, L et al. (1994) Identification of a B2 bradykinin receptor expressed by PC12 pheochromocytoma cells. Proc Natl Acad Sci U S A 91:4412-6
McCaffrey, P G; Luo, C; Kerppola, T K et al. (1993) Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 262:750-4