The goal of this proposed study is to provide the Principal Investigator (P.I.), John K. Neubert, D.D.S., with the opportunity to develop as an independent researcher to complement his clinical training in Orofacial Pain Management. The P.I.'s training will be conducted within the laboratories of the two sponsors of this project, Drs. Kruger and Spigelman, at the UCLA Schools of Medicine and Dentistry. Dr. Neubert's immediate career goals include completion of his Ph.D. in Oral Biology and remaining as an instructor at the UCLA Orofacial Pain Clinic. Long term goals include running a pain research laboratory and establishing an orofacial pain curriculum and clinic at a dental school. The research career development will include further training and experience in the areas of electrophysiology and histology to prepare the P.I. as an independent researcher. Chronic orofacial neuropathic pain (CONP) is a problem of considerable clinical relevance. Understanding the mechanisms underlying orofacial neuropathic pain maintenance becomes an important feature in striving to treat CONP. Experimental evidence from animal studies points to the involvement of inflammatory mediators and tachykinin neuropeptides in the mechanism underlying neuropathic pain. The goals of this study are to characterize the involvement and interactions of inflammatory cytokines and the tachykinin neuropeptide, substance P (SP), in the maintenance of orofacial neuropathic pain. Orofacial neuropathic pain will be induced in an established guinea pig model of trigeminal nerve injury. In vitro intracellular recordings and pharmacological studies and in vivo microdialysis will be utilized as methods for studying SP involvement in CONP. The peripheral involvement of inflammatory cytokines in CONP will be explored with immunohistochemical and light and electron microscopy techniques following trigeminal nerve entrapment. Determination of altered levels of neuropeptides and their interactions with inflammatory mediators, along with changes within the TRIG following neuropathic induction provides a novel, yet important area of investigation for characterizing pain transmission in the trigeminal system.
| Neubert, John K; Matsuka, Yoshizo; Maidment, Nigel T et al. (2002) Microdialysis in trigeminal ganglia. Brain Res Brain Res Protoc 10:102-8 |
| Matsuka, Y; Neubert, J K; Maidment, N T et al. (2001) Concurrent release of ATP and substance P within guinea pig trigeminal ganglia in vivo. Brain Res 915:248-55 |
| Neubert, J K; Maidment, N T; Matsuka, Y et al. (2000) Inflammation-induced changes in primary afferent-evoked release of substance P within trigeminal ganglia in vivo. Brain Res 871:181-91 |
