The transduction of painful stimuli into nerve impulses in pain-sensiti neurones is poorly understood. The proposed project will use cultured neurones from the dorsal root ganglion, which are known to respond to a variety of painful stimuli, and will examine the electrophysiological response of the neurones to bradykinin, capsaicin and noxious thermal stimuli. Techniques to be used will include whole-cell and cell-attached patch clamp, calcium imaging using confocal microscopy, and receptor identification using immunohistochemistry and in situ hybridisation. Stimuli will be applied using a rapid solution change method. The principal projects will include
(i) Biophysical characterisation of ion channels activated by bradykinin, capsaicin and thermal stimuli
(ii) An investigation of signal pathways and internal transmitters underlying activation of ion channels by noxious stimuli
(iii) An investigation of the mechanisms of response adaptation observed on repeated application of noxious stimuli
(iv) An investigation of signal pathways activated by B1 receptors, using neurones from a B2 knockout transgenic mouse.