title: Differential rostral projections of caudal brainstem neurons receiving trigeminal input after masseter inflammation.
abstract: To understand the functional significance of orofacial injury-induced neuronal activation, this study examined the rostral projection of caudal brainstem neurons that were activated by masseteric inflammation. Rats were injected with a retrograde tracer, Fluorogold, into the nucleus submedius of the thalamus (Sm), parabrachial nucleus (PB), lateral hypothalamus (LH), or medial ventroposterior thalamic nucleus (VPM) 7 days before injection of an inflammatory agent, complete Freund's adjuvant (CFA), into the masseter muscle. Rats were perfused at 2 hours after inflammation, and brainstem tissues were processed for Fos-Fluorogold double immunocytochemistry. Although there was no difference in Fos expression among the four groups (n=4 per site), the rostral projection of Fos-positive neurons showed dramatic differences. In the ventral portion of the trigeminal subnuclei interpolaris/caudalis (Vi/Vc) transition zone, the percentage of Fos-positive neurons projecting to the Sm (39.7%) was significantly higher than that projecting to the LH (5.4%) or VPM (5.6%; P<.001). The anesthesia alone also induced Fos expression in ventral Vi/Vc neurons, but these neurons did not project to Sm. In the caudal laminated Vc and dorsal Vi/Vc, the PB was the major site of rostral projection of Fos-positive neurons. In the caudal ventrolateral medulla and nucleus tractus solitarius, Fos-positive neurons projected to the Sm, PB, and LH. Most VPM-projecting neurons examined did not show Fos-like immunoreactivity after masseter inflammation. These findings emphasize the importance of the trigeminal Vi/Vc transition zone in response to orofacial deep tissue injury. Furthermore, the results differentiate the ventral and dorsal portions of the Vi/Vc transition zone, in that the Sm received projection mainly from activated neurons in the ventral Vi/Vc. The activation of Vi/Vc neurons and associated ascending pathways may facilitate somatoautonomic and somatovisceral integration and descending pain modulation after orofacial deep tissue injury.
authors.affiliation: Department of Oral and Craniofacial Biological Sciences, Dental School, and Program in Neuroscience, University of Maryland, Baltimore, Maryland 21201-1586, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikeda
authors.forename: Ryuji
authors.initials: R
authors.lastname: Terayama
authors.forename: Seong-Suk
authors.initials: SS
authors.lastname: Jue
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sugiyo
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000033:anatomy & histology / Q000378:metabolism; D005620:Freund's Adjuvant / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008406:Masseter Muscle / Q000187:drug effects / Q000294:innervation* / Q000473:pathology*; D009434:Neural Pathways / Q000033:anatomy & histology; D009474:Neurons / Q000166:cytology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000294:innervation; D014276:Trigeminal Nerve / Q000033:anatomy & histology* / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D016760:Proto-Oncogene Proteins c-fos; D005620:Freund's Adjuvant; D008012:Lidocaine