title: Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.
abstract: Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (<3%). pERK-NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain.
authors.affiliation: Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: dehi14017@g.nihon-u.ac.jp.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: katagiri.ayano@nihon-u.ac.jp.
authors.forename: Ayano
authors.initials: A
authors.lastname: Katagiri
authors.affiliation: Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: desi15006@g.nihon-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: mikuompm@tmd.ac.jp.
authors.forename: Lou
authors.initials: L
authors.lastname: Mikuzuki
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: kubo.asako@nihon-u.ac.jp.
authors.forename: Asako
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Periodontology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: deta14021@g.nihon-u.ac.jp.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: oohara.kinuyo@nihon-u.ac.jp.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Ohara
authors.affiliation: Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: lee.jun@nihon-u.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: gionhaku.nobuhito@nihon-u.ac.jp.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Gionhaku
authors.affiliation: Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: iinuma.toshimitsu@nihon-u.ac.jp.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Iinuma
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA. Electronic address: bereiter@umn.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Bereiter
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: iwata.kouichi@nihon-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000633:toxicity; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005157:Facial Pain / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism / Q000473:pathology*; D065823:Parabrachial Nucleus / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018689:Sensory System Agents / Q000633:toxicity; D018709:Statistics, Nonparametric; D013266:Stilbamidines / Q000378:metabolism; D014278:Trigeminal Nuclei / Q000473:pathology*; D020651:Ventral Thalamic Nuclei / Q000473:pathology
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018040:Receptors, Neurokinin-1; D018689:Sensory System Agents; D013266:Stilbamidines; D048049:Extracellular Signal-Regulated MAP Kinases; D002211:Capsaicin
keywords: Medulla; Parabrachial nucleus; Thalamic nucleus; Trigeminal nerve; Upper cervical cord; pERK