Renewal of support is requested for studies on neural mechanisms related to primary afferent input over small diameter (Adelta and C) fibers. The overall purpose is to better insight on how information conveyed by fine afferent fibers is transmitted and modulated at spinal terminations and, thereby, to uncover new strategies to control pain and abnormalities of other somatic sensations. The proposed work has three specific aims. One is to establish the nature of connections between the several types of neurons comprising the superficial dorsal horn (SDH) of the spinal cord, a region in which many thin fibers terminate. Another is to utilize structural and functional features of a set of SDH neurons labeled by green fluorescent protein (GFP) in a transgenic mouse as a tool to test the hypothesis that the SDH is comprised of modules of interconnected neurons.
A third aim i s to compare and contrast the actions of mediators, associated with descending control systems (e.g., serotonin, norepinephrine and hypocretin) over the spectrum of SDH neurons. Tight-seal, whole-cell, electrophysiological studies are to be done in vitro on slices prepared from spinal cord of rat and mouse, bred on purpose for animal experimentation. All three aims involve single, or two simultaneous recordings, from SDH neurons using pipette microelectrodes containing biocytin or lucifer yellow to delineate the morphology of the recorded cell. Infrared or a combination of infrared and fluorescence microscopy will be used to guide selection of neurons to be studied. Electrophysiological characterizations will include responsiveness to: i) stimulation of the segmental dorsal root, ii) passage of current through the recording electrode, iii) activation of a simultaneously recorded neuron and iv) selectively acting pharmaceutical agents. Immunocytochemical studies will be used to complement the structural and pharmacological analyses to aid in establishing mediators involved in linkages between SDH neurons.
| Perl, Edward R (2011) Pain mechanisms: a commentary on concepts and issues. Prog Neurobiol 94:20-38 |
| Light, Alan R; Perl, Edward R (2003) Unmyelinated afferent fibers are not only for pain anymore. J Comp Neurol 461:137-9 |
