Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach

Hiroto Saito, Ayano Katagiri, Shinji Okada, Lou Mikuzuki, Asako Kubo, Tatsuro Suzuki, Kinuyo Ohara, Jun Lee, Nobuhito Gionhaku, Toshimitsu Iinuma, David A. Bereiter, Koichi Iwata

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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.

Original languageEnglish (US)
Pages (from-to)124-136
Number of pages13
JournalExperimental Neurology
StatePublished - Jul 1 2017

Bibliographical note

Funding Information:
This work was supported by the Japanese Association for Oral Biology (Grant-in-Aid for Young Scientists to AK); JSPS KAKENHI Grant Number 15K21410 to AK; in part by a grant from the National Institutes of Health (USA, EY021447 to DB); Research Grants from Sato and Uemura Funds from Nihon University School of Dentistry; and a Grant from Dental Research Center of Nihon University School of Dentistry.

Publisher Copyright:
© 2017 Elsevier Inc.


  • Medulla
  • Parabrachial nucleus
  • Thalamic nucleus
  • Trigeminal nerve
  • Upper cervical cord
  • pERK


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