Little is known about the mechanisms underlying 5 HT induced pain and inflammation. Thirteen 5HT receptor subtypes have been cloned from rat tissue, and the investigator has found at least 6 of these subtypes in peripheral sensory and sympathetic neurons. Their role in inflammation and nociception remains unclear, nor is it clear how these receptors interact with general anesthetics.
In specific aim 1, the investigator will determine the role of 5-HT receptor subtypes in modulating nociceptive and proinflammatory functions of primary afferent nociceptors using extracellular single unit recording and c-fos expression in dorsal horn neurons. Efferent pathways will be evaluated using a capsaicin-stimulated plasma extravasation technique in synovial space.
Specific aim 2 will evaluate the role of 5-HT receptors in sympathetically mediated inflammatory responses in the same model, and specific aim 3 will evaluate the interaction of these responses with both injectable and inhaled general anesthetics. This is an approach to reducing the degree of post-operative inflammation and pain, thereby decreasing post-operative morbidity.
