Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
    • Special Collections
  • EDITORIAL BOARD
    • Editorial Board
    • ECR Advisory Board
    • Journal Staff
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
    • Accessibility
  • SUBSCRIBE

User menu

  • Log out
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log out
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
    • Special Collections
  • EDITORIAL BOARD
    • Editorial Board
    • ECR Advisory Board
    • Journal Staff
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
    • Accessibility
  • SUBSCRIBE
PreviousNext
Research Articles, Neurobiology of Disease

Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache

Rodrigo Noseda, Agustin Melo-Carrillo, Rony-Reuven Nir, Andrew M. Strassman and Rami Burstein
Journal of Neuroscience 6 March 2019, 39 (10) 1867-1880; https://doi.org/10.1523/JNEUROSCI.2153-18.2018
Rodrigo Noseda
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rodrigo Noseda
Agustin Melo-Carrillo
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rony-Reuven Nir
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew M. Strassman
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rami Burstein
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rami Burstein
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    Anterograde tracing of C2 DRG peripheral axons to the posterior dura (extracranial component). A, Illustration of the rat's skull view from behind showing intra-ganglionar injection of rAAV-GFP viral vector into C2 DRG. B, Transversal view of a C2 DRG section showing GFP expression in successfully transduced cells (green, left), some of which were also immunoreactive to CGRP (red, middle). Superimposition of these images and DAPI (blue) is displayed at the right with white arrowheads indicating double-labeled cells (yellow). C, Cross-section of the whole neck at the level of C1 vertebra showing the distribution and trajectories of GFP-labeled nerves and fibers traveling along blood vessels (BV), fascia, and muscle from C2 DRG to the cranium. The image shows the left dorsolateral quadrant of the neck and was created by stitching 268 high-resolution images into a single composite. Numbers and frames indicate the areas where the images displayed at the right and bottom were taken. The only not-numbered image was taken from another cross-section of the neck in the same animal. D, Cervical nerves and bundles of fibers expressing GFP were observed crossing neck muscles, traveling along blood vessels and fascia before entering the cranium in the occipital region through (E) a canal between the occipital bone (occ) and the periotic capsule (pcap) (1), emissary canals near the occipital condyle (2), the hypoglossal canal (3), foramen magnum (fmag) (4), and jugular foramen (5). Interparietal bone (ipar), parietal bone (par). Scale bars, 100 μm.

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2.

    Anterograde tracing of C2 DRG peripheral axons in the posterior dura (intracranial component). A, Flat mount of the dura overlying the cerebellum showing GFP-labeled axons from C2 DRG spreading within the dura immediately after entering the cranium. These GFP-labeled dural axons were immunoreactive to CGRP (red) as evidenced in the superimposition of images at the bottom, where white arrowheads indicate double labeling of these axons (yellow) in the DAPI (blue) counterstained dura. B, Representative examples of GFP-labeled axons spreading extensively within the posterior dura overlying the cerebellum (left), large intra-cranial blood vessels (right), and (C) the dura covering the upper cervical segments of the spinal cord. D, Reconstruction of the GFP-labeled axons shown in A–C. Inset, Illustration of the rat brain showing the region of interest. Scale bars, 100 μm.

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3.

    Retrograde labeling in C2 DRG from the posterior dura. A, Illustration of the rat's skull view from behind showing the area of FG application (green) on the posterior dura. B, Transversal view of a C2 DRG section showing retrogradely-labeled neurons filled with FG near the anterior edge of the left ganglion. C, A proportion of FG-labeled neurons (green) in C2 DRG was also immunoreactive to CGRP, TRPV1, or IB4 (red). Images in the left column were created by superimposition of the images in the right column. Filled arrowheads point to FG-positive cells. Open arrowheads indicate double-labeled cells with FG and with each of the three markers of sensory neurons used (yellow). Scale bars, 100 μm.

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4.

    Electrophysiological characterization of posterior dura-sensitive neurons in C2–C4 dorsal horn. A, Illustration of the rat's skull, exposed posterior dura, neck muscles, and skin showing the mapping of all RFs obtained from a single dura-sensitive neuron at baseline. B, Identification of C2–C4 neurons responding to electrical and mechanical stimulation of the posterior dura, neck muscle, and skin.

  • Figure 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5.

    Schematic representation of C2 to C4 spinal cord segments showing the recording sites marked by electrolytic lesions made at the end of each experiment. Red dots represent recording sites where neurons displaying sensitized responses were found. An example of these lesions in C2 spinal cord segment is shown in the dark-field image at the right. Scale bar, 500 μm.

  • Figure 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6.

    RFs and neuronal responses to mechanical stimulation of the posterior dura. A, Illustration of the rat's skull showing the area of exposition of the posterior dura (gray) and dural RFs of C2–C4 spinal cord dura-sensitive neurons measured during mechanical stimulation with VFH at baseline (dark blue) and 2 h after application of IS (light blue). B, C, Responses of individual neurons to mechanical stimulation of the posterior dura before (B) and after IS (C). Neurons were classified as sensitized (red) if their response magnitude increased by at least 50% after IS. Numbers in parenthesis represent firing rate in mean spikes/s during baseline (10 s) and stimulation (10 s). Shaded areas indicate the period of mechanical stimulation.

  • Figure 7.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 7.

    RFs and neuronal responses to mechanical stimulation of neck muscles. A, Illustration of superficial and deep group of neck muscles showing the most sensitive area (blue) to mechanical stimulation with VFH. B, C, Responses of individual neurons to mechanical stimulation of muscle RFs before (B) and after IS (C). Neurons were classified as sensitized (red) if their response magnitude increased by at least 50% after IS. Numbers in parenthesis represent firing rate in mean spikes/s during baseline (10 s) and stimulation (10 s). Shaded areas indicate the period of mechanical stimulation.

  • Figure 8.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 8.

    RFs and neuronal responses to innocuous and noxious mechanical stimulation of the skin. A, Illustration of the rat's head and neck showing the cutaneous RFs of C2–C4 spinal cord dura-sensitive neurons measured during mechanical stimulation at baseline (dark blue) and 2 h after application of IS (light blue). B, Responses of individual neurons to mechanical stimulation (brush, pressure, and pinch) of the skin before (left columns) and after IS (right columns). Neurons were classified as sensitized (red) if their response magnitude increased by at least 50% after IS. Numbers in parenthesis represent firing rate in mean spikes/s during baseline (10 s) and stimulation (10 s). Shaded areas indicate the period of mechanical stimulation.

  • Figure 9.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 9.

    Neuronal responses of sensitized neurons to mechanical stimulation of (A) the posterior dura, (B) neck muscle, and (C) skin (brush, pressure, and pinch) before (green) and 2 h after application of IS (red). Thick lines and shadowed areas represent mean and SE, respectively.

Back to top

In this issue

The Journal of Neuroscience: 39 (10)
Journal of Neuroscience
Vol. 39, Issue 10
6 Mar 2019
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Advertising (PDF)
  • Ed Board (PDF)
Email

Thank you for sharing this Journal of Neuroscience article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache
Rodrigo Noseda, Agustin Melo-Carrillo, Rony-Reuven Nir, Andrew M. Strassman, Rami Burstein
Journal of Neuroscience 6 March 2019, 39 (10) 1867-1880; DOI: 10.1523/JNEUROSCI.2153-18.2018

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache
Rodrigo Noseda, Agustin Melo-Carrillo, Rony-Reuven Nir, Andrew M. Strassman, Rami Burstein
Journal of Neuroscience 6 March 2019, 39 (10) 1867-1880; DOI: 10.1523/JNEUROSCI.2153-18.2018
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • cerebellum
  • cervical
  • DRG
  • dura
  • migraine
  • neck muscles

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

Research Articles

  • Vocal error monitoring in the primate auditory cortex
  • CaMKIIβ-mediated phosphorylation enhances protein stability of spastin to promote neurite outgrowth
  • Neural Distinction between Visual Word and Object Recognition: An fMRI Study Using Pictographs
Show more Research Articles

Neurobiology of Disease

  • Unveiling cortical criticality changes along the prodromal to the overt continuum of alpha-synucleinopathy
  • Atypical Retinal Ganglion Cell Function in a Mouse Model of Fragile X Syndrome
  • Basal forebrain-ventral tegmental area glutamatergic pathway promotes emergence from isoflurane anesthesia in mice
Show more Neurobiology of Disease
  • Home
  • Alerts
  • Follow SFN on BlueSky
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Notice
  • Contact
  • Accessibility
(JNeurosci logo)
(SfN logo)

Copyright © 2025 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.