The somatic sensations-touch, temperature, muscle position, pain- are transduced by sensory neurons, each of which mediates a particular sensation at a particular site on the body. Because they are clustered in groups of about 10,000, the cell bodies of sensory neurons can be readily dissected, dissociated, and placed in tissue culture where cellular and molecular studies are possible. However, dissection from the animal destroy the ability to identify the sensory modality of a neuron, and thereby eliminates the changes to search for distinguishing features between the different sensations. We have partially solved this problem by developing two novel methods to label a) stretch receptors innervating jaw muscle and b) nociceptors innervating tooth pulp. The cells are labeled in the animal and later identified by fluorescence microscopy in primary tissue culture. In general, this project is basic in nature, aiming to describe molecular differences between these neurons that transduce different somatic sensations. Clinical relevance might arise because such differences may suggest novel methods to suppress pain without affecting other sensations. The proposed experiments will compare the electrical and pharmacological properties of the stretch receptors and nociceptors as well as exploring the plasticity of gene transcription in the nociceptors. Specifically, the first aim will determine if compounds that inhibit neurotransmission by sensory neurons differentially affect the two types of cells. This will be tested both by inhibition of Ca/2+ channels, measured with standard patch clamp methods, and a novel method for recording neurotransmitter release from sensory neurons.
The second aim will compare the responses of the two cell types to several compounds that open ligand-gated channels on sensory neurons. Although the mechanisms are uncertain, these channels are thought to be involved in sensory transduction; this theory would predict differences in channel activity on neurons transducing different sensations.
The third aim will be tested through observation of phosphorylated CREB, a phosphorylation- stimulated transcription factor, and through PCR for two neuropeptides in individual cells using an improved method described in this proposal.
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| Yagi, Junichi; Wenk, Heather N; Naves, Ligia A et al. (2006) Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. Circ Res 99:501-9 |
| Molliver, Derek C; Cook, Sean P; Carlsten, Julie A et al. (2002) ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2. Eur J Neurosci 16:1850-60 |
