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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS037224-02
Application #
2714661
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Kitt, Cheryl A
Project Start
1997-07-10
Project End
2002-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Pietruck, Christian; Grond, Stefan; Xie, Guo-Xi et al. (2003) Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediated synovial neurogenic plasma extravasation. Anesth Analg 96:1397-402, table of contents
Meuser, Thomas; Pietruck, Christian; Gabriel, Anja et al. (2002) 5-HT7 receptors are involved in mediating 5-HT-induced activation of rat primary afferent neurons. Life Sci 71:2279-89
Pietruck, C; Xie, G X; Sharma, M et al. (1999) Multiple splice patterns of cyclic AMP response element-binding protein mRNA in the central nervous system of the rat. Brain Res Mol Brain Res 69:286-9
Xie, G X; Meuser, T; Pietruck, C et al. (1999) Presence of opioid receptor-like (ORL1) receptor mRNA splice variants in peripheral sensory and sympathetic neuronal ganglia. Life Sci 64:2029-37
Pietruck, C; Xie, G X; Sharma, M et al. (1999) Alternative exon splicing of cyclic AMP response element-binding protein in peripheral sensory and sympathetic ganglia of the rat. Life Sci 65:2205-13