Although neuropeptides are known to exert a wide range of pro-inflammatory effects after administration into normal tissue, relatively little is known about the physiologic mechanisms regulating neuropeptide release during tissue inflammation. Our research group has developed a technique for collecting inflammatory mediators including neuropeptides, by implanting microdialysis probes into surgical wounds of awake post-oral surgery patients, or in anesthetized rats following tissue injury. Although substantial levels of immunoreactive substance P (i.e., about 4-5 nM) are released into the surgical wounds of dental pain patients, our preliminary studies do not identify the inflammatory mediators which mediate release of immunoreactive substance P (iSP). Accordingly, the present multidisciplinary studies are designed to determine which inflammatory mediators regulate the initiation of neurogenic inflammation. The studies will collect and measure tissue levels of iSP as a marker for the initiation of neurogenic inflammation. Specific studies will: Clinical studies: 1. Determine the tissue origin of iSP collected from microdialysis probes implanted into the surgical wounds of awake patients following extraction of impacted mandibular third molars. 2. Determine the peripheral effects of drugs which modulate neurogenic inflammation (mepivacaine vs capsaicin), and prototype analgesic drugs (codeine, ibuprofen), acetaminophen, methylprednisolone) for reducing tissue levels of iSP, and tissue levels of immunoreactive prostaglandin E2 (iPGE2), leukotriene B4 (iLTB4) and bradykinin (iBK). Animal studies; 1. Evaluate the effects of prototype analgesic drugs for reducing tissue levels of iSP, and tissue levels of iPGE2, iLTB4 and iBK collected from microdialysis probes implanted into the surgical wounds of anesthetized rats following surgical extraction of mandibular incisor teeth. 2. Determine the role of prostanoids and their respective receptor sub- types, using selective agonists and antagonists, on altering tissue levels of iSP). 3. Determine the role of kinins and the B1 and B2 receptors, using selective agonists and antagonists, on altering tissue levels of iSP. 4 Determine the role of leukotrienes and their respective receptor sub- types, using selective agonists and antagonists, on altering tissue levels of iSP. Collectively, these studies will identify the inflammatory mediators which initiate neurogenic inflammation.
| Ulrich-Lai, Y M; Flores, C M; Harding-Rose, C A et al. (2001) Capsaicin-evoked release of immunoreactive calcitonin gene-related peptide from rat trigeminal ganglion: evidence for intraganglionic neurotransmission. Pain 91:219-26 |
| Roszkowski, M T; Swift, J Q; Hargreaves, K M (1997) Effect of NSAID administration on tissue levels of immunoreactive prostaglandin E2, leukotriene B4, and (S)-flurbiprofen following extraction of impacted third molars. Pain 73:339-45 |
