Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Pharmacological Reviews
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Pharmacological Reviews

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit Pharm Rev on Facebook
  • Follow Pharm Rev on Twitter
  • Follow ASPET on LinkedIn
Review ArticleReview Article

Neuroinflammation and Comorbidity of Pain and Depression

A. K. Walker, A. Kavelaars, C. J. Heijnen and R. Dantzer
Lynette C. Daws, ASSOCIATE EDITOR
Pharmacological Reviews January 2014, 66 (1) 80-101; DOI: https://doi.org/10.1124/pr.113.008144
A. K. Walker
Department of Symptom Research, Laboratory of Neuroimmunology of Cancer-Related Symptoms, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Kavelaars
Department of Symptom Research, Laboratory of Neuroimmunology of Cancer-Related Symptoms, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. J. Heijnen
Department of Symptom Research, Laboratory of Neuroimmunology of Cancer-Related Symptoms, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Dantzer
Department of Symptom Research, Laboratory of Neuroimmunology of Cancer-Related Symptoms, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lynette C. Daws
Department of Symptom Research, Laboratory of Neuroimmunology of Cancer-Related Symptoms, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Roles: ASSOCIATE EDITOR
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Comorbid depression and chronic pain are highly prevalent in individuals suffering from physical illness. Here, we critically examine the possibility that inflammation is the common mediator of this comorbidity, and we explore the implications of this hypothesis. Inflammation signals the brain to induce sickness responses that include increased pain and negative affect. This is a typical and adaptive response to acute inflammation. However, chronic inflammation induces a transition from these typical sickness behaviors into depression and chronic pain. Several mechanisms can account for the high comorbidity of pain and depression that stem from the precipitating inflammation in physically ill patients. These mechanisms include direct effects of cytokines on the neuronal environment or indirect effects via downregulation of G protein–coupled receptor kinase 2, activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase that generates neurotropic kynurenine metabolites, increased brain extracellular glutamate, and the switch of GABAergic neurotransmission from inhibition to excitation. Despite the existence of many neuroimmune candidate mechanisms for the co-occurrence of depression and chronic pain, little work has been devoted so far to critically assess their mediating role in these comorbid symptoms. Understanding neuroimmune mechanisms that underlie depression and pain comorbidity may yield effective pharmaceutical targets that can treat both conditions simultaneously beyond traditional antidepressants and analgesics.

Footnotes

  • This work was supported by the University of Texas MD Anderson Cancer Center and National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants R01-NS073939 and R01-NS074999]. The work of A.K. is also supported by a STARS [“Science and Technology Acquisition and Retention”] award of the University of Texas System.

  • R.D. is a consultant with Ironwood Pharma (Cambridge, MA).

  • The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • dx.doi.org/10.1124/pr.113.008144.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

PharmRev articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Pharmacological Reviews: 66 (1)
Pharmacological Reviews
Vol. 66, Issue 1
1 Jan 2014
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Pharmacological Reviews 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.
Neuroinflammation and Comorbidity of Pain and Depression
(Your Name) has forwarded a page to you from Pharmacological Reviews
(Your Name) thought you would be interested in this article in Pharmacological Reviews.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Review ArticleReview Article

Mechanisms of Inflammation-Induced Depression and Pain

A. K. Walker, A. Kavelaars, C. J. Heijnen and R. Dantzer
Pharmacological Reviews January 1, 2014, 66 (1) 80-101; DOI: https://doi.org/10.1124/pr.113.008144

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Review ArticleReview Article

Mechanisms of Inflammation-Induced Depression and Pain

A. K. Walker, A. Kavelaars, C. J. Heijnen and R. Dantzer
Pharmacological Reviews January 1, 2014, 66 (1) 80-101; DOI: https://doi.org/10.1124/pr.113.008144
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • I. Introduction: Comorbid Depression and Pain
    • II. Peripheral Inflammation and Its Propagation to the Brain
    • III. Peripheral Inflammation Is Associated with Pain and Depression
    • IV. Brain Inflammation Is Associated with Pain and Depression
    • V. Possible Molecular Mechanisms
    • VI. Conclusion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Review of Natural Language Processing in Pharmacology
  • PHARMACOGENOMICS: Driving Personalized Medicine
  • Potassium Channels in Parkinson's Disease
Show more Review Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Pharmacological Reviews
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacology Research & Perspectives
ISSN 1521-0081 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics