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.
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