Volume 10 Supplement 1

Proceedings of the Seventh Scientific Meeting of The TMJ Association

Open Access

A cellular mechanism of interactions between pain and depression

  • Hyangin Kim1,
  • Michael F McCabe1,
  • Grewo Lim1,
  • Lucy Chen1 and
  • Jianren Mao1
Molecular Pain201410(Suppl 1):O10

https://doi.org/10.1186/1744-8069-10-S1-O10

Published: 15 December 2014

Background

Depression is a common comorbid condition of chronic pain. The current mainstay of managing comorbid chronic pain uses combination drug therapy including opioid analgesics and antidepressants. However, the cellular mechanism underlying the comorbid interaction between chronic pain and depression remains unclear.

Materials and methods

Using rat models of genetically predisposed [Wistar-Kyoto (WKY) rats] or induced depressive behavior combined with persistent nociception, we examined whether 1) brain IDO1 (a rate-limiting enzyme in tryptophan metabolism) expression and activity would be increased in rats with genetically predisposed or induced depressive behavior, 2) rats with depressive behavior would exhibit exacerbated nociceptive behavior, and 3) brain IDO1 upregulation would be contributory to both depressive and nociceptive behaviors. Depressive behaviors were assessed by using forced swimming test, sucrose preference test, tail suspension test, and open field test. Nociceptive behaviors were assessed using von Frey filaments and hind-paw withdrawal to radiant heat stimulation. RT-PCR, Western blotting, HPLC, ELISA, immunohistochemistry and cell culture were used in the study.

Results

We demonstrate that brain IDO1 expression critically contributes to the comorbid interaction between pain and depression.(1) IDO1 expression was elevated in the hippocampus of rats with either genetically predisposed or anhedonia-induced depressive behavior. (2) Rats with elevated IDO1 expression exhibited a lower baseline mechanical and thermal nociceptive threshold, whereas depressive behavior was exacerbated in rats with persistent nociception.(3) IDO1 upregulation was mediated by the IL-6/JAK/STAT signaling, resulting in a shift of tryptophan metabolism toward the IDO pathway as well as a low serotonin content in the hippocampus. (4) Inhibition of IDO1 activity or IL-6/JAK/STAT-mediated IDO1 upregulation concurrently attenuated nociceptive and depressive behaviors in the same rats.

Conclusions

The results indicate that brain IDO1 expression critically contributes to the comorbid interaction between pain and depression and suggest that targeting brain IDO1 activity may offer a new therapeutic method for the treatment of comorbid chronic pain.

Declarations

Acknowledgements

This study was supported by NIH grants R01DE18214 and R01DE18538.

Authors’ Affiliations

(1)
MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School

Copyright

© Kim et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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