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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\u2010RVM pathway after inflammation. No double\u2010labeled neurons were found in the dorsal Vi\/Vc and laminae I\u2013IV of Vc. Injection of an anterograde tracer, <jats:italic>Phaseolus vulgaris<\/jats:italic> 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\u2010selective neurotoxin, ibotenic acid, significantly reduced inflammation\u2010induced Fos expression as well as the number of FluoroGold\/Fos double\u2010labeled neurons in the ventral Vi\/Vc (<jats:italic>P<\/jats:italic> &lt; 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 (<jats:italic>P<\/jats:italic> &lt; 0.05\u20130.01). The present study demonstrates reciprocal connections between the ventral Vi\/Vc transition zone and RVM. The Vi\/Vc\u2010RVM pathway is activated after orofacial deep tissue injury and plays a critical role in facilitating orofacial hyperalgesia. J. Comp. Neurol. 493:510\u2013523, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.20797","type":"journal-article","created":{"date-parts":[[2005,11,22]],"date-time":"2005-11-22T16:55:31Z","timestamp":1132678531000},"page":"510-523","source":"Crossref","is-referenced-by-count":78,"title":["Trigeminal transition zone\/rostral ventromedial medulla connections and facilitation of orofacial hyperalgesia after masseter inflammation in rats"],"prefix":"10.1002","volume":"493","author":[{"given":"Shinichi","family":"Sugiyo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohide","family":"Takemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Dubner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902500305"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(82)90297-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)91156-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90101-1"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90955-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00095-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00476-6"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-12-05129.2002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902140105"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00297-V"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.71.6.2430"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90183-X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1152\/jn.1983.49.4.948","article-title":"Descending inhibitory influences from periaqueductal gray, nucleus raphe magnus, and adjacent reticular formation. 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