Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression.
Neuropathic pain is a complex chronic condition characterized by various sensory, cognitive, and affective symptoms. A large percentage of patients with neuropathic pain are also afflicted with depression and anxiety disorders, a pattern that is also seen in animal models. Furthermore, clinical and preclinical studies indicate that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major risk factor for depression. We investigated whether chronic pain and stress affect similar molecular mechanisms and whether chronic pain can affect gene expression patterns that are involved in depression. Using two mouse models of neuropathic pain and depression [spared nerve injury (SNI) and chronic unpredictable stress (CUS)], we performed next-generation RNA sequencing and pathway analysis to monitor changes in gene expression in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal gray (PAG). In addition to finding unique transcriptome profiles across these regions, we identified a substantial number of signaling pathway-associated genes with similar changes in expression in both SNI and CUS mice. Many of these genes have been implicated in depression, anxiety, and chronic pain in patients. Our study provides a resource of the changes in gene expression induced by long-term neuropathic pain in three distinct brain regions and reveals molecular connections between pain and chronic stress.
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Giannina
http://orcid.org/0000-0003-3734-394X
G
Descalzi
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vasiliki
http://orcid.org/0000-0003-2072-8974
V
Mitsi
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Immanuel
I
Purushothaman
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sevasti
http://orcid.org/0000-0002-0596-4840
S
Gaspari
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kleopatra
http://orcid.org/0000-0002-5902-5523
K
Avrampou
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yong-Hwee Eddie
YE
Loh
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Li
http://orcid.org/0000-0002-5190-2851
L
Shen
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. venetia.zachariou@mssm.edu.
Venetia
http://orcid.org/0000-0003-3194-8569
V
Zachariou
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D059350:Chronic Pain / Q000503:physiopathology; D016000:Cluster Analysis; D003863:Depression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism*; D009437:Neuralgia / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000378:metabolism / Q000503:physiopathology; D010487:Periaqueductal Gray / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics; D013315:Stress, Psychological / Q000503:physiopathology