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
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • 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
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
This Week in The Journal

This Week in The Journal

Teresa Esch [Ph.D.]
Journal of Neuroscience 13 February 2019, 39 (7) 1135; DOI: https://doi.org/10.1523/JNEUROSCI.twij.39.07.2019
Teresa Esch
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Teresa Esch
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Role of Spinal Microglia in Stress-Induced Pain Sensitivity

Caroline M. Sawicki, January K. Kim, Michael D. Weber, Timothy D. Faw, Daniel B. McKim, et al.

(see pages 1139–1149)

Stressful experiences activate the sympathetic nervous system, resulting in norepinephrine release in various tissues. Besides increasing heart rate and blood pressure to increase nutrient supply to muscles needed for fighting or flight, norepinephrine activates the immune system to enable quick responses to tissue damage. And prolonged or repeated stress alters the balance of different types of immune cells—including microglia, the primary immune cells of the CNS. Specifically, stress increases the proportion of cells with proinflammatory phenotypes. Proinflammatory cytokines released by such cells contribute to the psychological effects of stress, including the promotion of withdrawal from physical and social activity. These behaviors likely facilitate recovery from acute stressors, but they may become maladaptive after chronic stress, leading to depression and anxiety disorders (Weber et al., 2017 Neuropsychopharmacology 42:46).

In addition to psychological effects, both stress and inflammation have been linked to the development of chronic pain. Sawicki et al. therefore asked whether stress increases pain sensitivity by activating microglia. To answer this question, they subjected mice to repeated social defeat, which was previously shown to increase mechanical pain sensitivity, activate microglia in the brain, and produce anxiety-like behaviors. Repeated social defeat also increased labeling of P2Y12, a receptor involved in microglial chemotaxis, in the cap of the dorsal horn, the target of peripheral pain fibers. Levels of several proinflammatory cytokines and their receptors were also elevated in the spinal cord of stressed mice, but no peripheral immune cells were detected in the spinal cord. Importantly, after microglia were eliminated using a pharmacological agent, repeated social defeat no longer induced mechanical hypersensitivity, and some stress-induced increases in cytokines and receptors were attenuated.

These results indicate that social stress can increase pain sensitivity in the absence of injury by activating microglia in the spinal cord's dorsal horn. Elucidating the molecular mechanisms of this effect might therefore lead to improved treatments for stress-associated chronic pain conditions.

Effects of Amygdala Cannabinoids on Fear and Anxiety

Maria Morena, Robert J. Aukema, Kira D. Leitl, Asim J. Rashid, Haley A. Vecchiarelli, et al.

(see pages 1275–1292)

Cannabinoids influence emotions, including fear and anxiety, by acting on type 1 receptors (CB1Rs) in the amygdala, hippocampus, prefrontal cortex, and other brain areas. Neurons can produce two types of endocannabinoids, N-arachidonylethanolamide (AEA; released tonically) and 2-arachidonoylglycerol (2-AG; released when cells are highly activated). These molecules act on CB1Rs on presynaptic terminals of GABAergic, glutamatergic, and neuromodulatory neurons, and they reduce neurotransmitter release. CB1R activation usually reduces anxiety and relaxes people. Similarly, activation of CB1Rs in rodents typically reduces fear responses and anxiety-like behaviors (e.g., avoidance of bright rooms and open spaces), whereas reducing CB1R activity has the opposite effects. But sometimes people experience paranoia and panic attacks after using exogenous cannabinoids, and anxiety-like effects can be elicited in rodents when high doses of cannabinoids are administered (Lutz et al., 2015 Nat Rev Neurosci 16:705). These opposing effects might stem from differences in activation of CB1Rs across neuron types and brain areas.

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

Increasing FAAH in BLA pyramidal neurons reduces AEA levels, leading to increases in presynaptic GABA release and reduced expression of fear and anxiety-like behaviors. See Morena et al. for details.

To elucidate the role of endocannabinoid signaling in the amygdala, Morena et al. used a virus to overexpress fatty acid amide hydrolase (FAAH), an enzyme that breaks down AEA, primarily in pyramidal neurons of the basolateral nucleus of the amygdala (BLA) in rats. As expected, this transiently reduced AEA levels. Based on previous work, the authors predicted that overexpressing FAAH would increase stress responses and produce an anxiety-like state. They found the opposite: when FAAH was overexpressed, stress-induced elevation of blood corticosterone levels was attenuated and rats were less likely to avoid a lighted chamber or the open arms of an elevated plus maze. FAAH overexpression did not impair fear conditioning, but it reduced responses to fear-associated stimuli on subsequent days. Importantly, the reduction in fear responses was blocked by antagonists of GABAA receptors, but not of glutamate receptors, in the BLA.

These results suggest that pyramidal neurons in the BLA tonically release AEA, which reduces GABA release from inhibitory inputs. Overexpressing FAAH increases hydrolysis of AEA, thus disinhibiting GABA release. Consequently, pyramidal cells are inhibited and less likely to evoke fear and anxiety-like behaviors. Notably, previous work suggested that increases in FAAH during acute stress reduces the effects of AEA on glutamatergic inputs to BLA pyramidal cells, thus increasing these cells' output. Future work should determine how such synapse-specific effects of AEA might be achieved.

Footnotes

  • This Week in The Journal was written by Teresa Esch, Ph.D.

Back to top

In this issue

The Journal of Neuroscience: 39 (7)
Journal of Neuroscience
Vol. 39, Issue 7
13 Feb 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.
This Week in The Journal
(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
This Week in The Journal
Teresa Esch [Ph.D.]
Journal of Neuroscience 13 February 2019, 39 (7) 1135; DOI: 10.1523/JNEUROSCI.twij.39.07.2019

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
This Week in The Journal
Teresa Esch [Ph.D.]
Journal of Neuroscience 13 February 2019, 39 (7) 1135; DOI: 10.1523/JNEUROSCI.twij.39.07.2019
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Role of Spinal Microglia in Stress-Induced Pain Sensitivity
    • Effects of Amygdala Cannabinoids on Fear and Anxiety
    • Footnotes
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

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

  • This Week in The Journal
  • This Week in The Journal
  • This Week in The Journal
Show more This Week in The Journal
  • Home
  • Alerts
  • 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 Policy
  • Contact
(JNeurosci logo)
(SfN logo)

Copyright © 2022 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.