title: Trigeminal transition zone/rostral ventromedial medulla connections and facilitation of orofacial hyperalgesia after masseter inflammation in rats.
abstract: Recent studies have implicated a role for the trigeminal interpolaris/caudalis (Vi/Vc) transition zone in response to orofacial injury. Using combined neuronal tracing and Fos protein immunocytochemistry, we investigated functional connections between the Vi/Vc transition zone and rostral ventromedial medulla (RVM), a key structure in descending pain modulation. Rats were injected with a retrograde tracer, FluoroGold, into the RVM 7 days before injection of an inflammatory agent, complete Freund's adjuvant, into the masseter muscle and perfused at 2 hours postinflammation. A population of neurons in the ventral Vi/Vc overlapping with caudal ventrolateral medulla, and lamina V of the trigeminal subnucleus caudalis (Vc), exhibited FluoroGold/Fos double staining, suggesting the activation of the trigeminal-RVM pathway after inflammation. No double-labeled neurons were found in the dorsal Vi/Vc and laminae I-IV of Vc. Injection of an anterograde tracer, Phaseolus vulgaris leucoagglutinin, into the RVM resulted in labeling profiles overlapped with the region that showed FluoroGold/Fos double labeling, suggesting reciprocal connections between RVM and Vi/Vc. Lesions of Vc with a soma-selective neurotoxin, ibotenic acid, significantly reduced inflammation-induced Fos expression as well as the number of FluoroGold/Fos double-labeled neurons in the ventral Vi/Vc (P<0.05). Compared with control rats, lesions of the RVM (n=6) or Vi/Vc (n=6) with ibotenic acid led to the elimination or attenuation of masseter hyperalgesia/allodynia developed after masseter inflammation (P<0.05-0.01). The present study demonstrates reciprocal connections between the ventral Vi/Vc transition zone and RVM. The Vi/Vc-RVM pathway is activated after orofacial deep tissue injury and plays a critical role in facilitating orofacial hyperalgesia.
authors.affiliation: Department of Biomedical Sciences, Dental School, and Program in Neuroscience, University of Maryland, Baltimore, Maryland 21201-1586, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sugiyo
authors.forename: Motohide
authors.initials: M
authors.lastname: Takemura
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
mesh_terms: D000818:Animals; D005157:Facial Pain / Q000503:physiopathology*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008406:Masseter Muscle / Q000294:innervation / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014276:Trigeminal Nerve / Q000166:cytology / Q000503:physiopathology*; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos