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Trigeminal transition zone/rostral ventromedial medulla connections and facilitation of orofacial hyperalgesia after masseter inflammation in rats
Author(s) -
Sugiyo Shinichi,
Takemura Motohide,
Dubner Ronald,
Ren Ke
Publication year - 2005
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20797
Subject(s) - rostral ventromedial medulla , orofacial pain , anterograde tracing , retrograde tracing , anatomy , nociception , chemistry , hyperalgesia , neuroscience , biology , medicine , central nervous system , receptor , radiology
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. J. Comp. Neurol. 493:510–523, 2005. © 2005 Wiley‐Liss, Inc.