Journal
MOLECULAR PSYCHIATRY
Volume 15, Issue 4, Pages 404-414Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2009.91
Keywords
spared nerve injury; depressive-like behavior; interleukin-1 beta; stress; glucocorticoid; neuropathic pain
Funding
- American Heart Association
- National Institute of Neurological Disorders and Stroke Behavioral Core [P30 NS045758, 5R01NR010806]
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The physiological link between neuropathic pain and depression remains unknown despite a high comorbidity between these two disorders. A mouse model of spared nerve injury (SNI) was used to test the hypothesis that nerve injury precipitates depression through the induction of inflammation in the brain, and that prior exposure to stress exacerbates the behavioral and neuroinflammatory consequences of nerve injury. As compared with sham surgery, SNI induced mechanical allodynia, and significantly increased depressive-like behavior. Moreover, SNI animals displayed increased interleukin-1 beta (IL-1 beta) gene expression within the frontal cortex and concurrent increases in the expression of glial fibrillary acidic protein (GFAP) within the periaqueductal grey (PAG). Additionally, exposure to chronic restraint stress for 2 weeks before SNI exacerbated mechanical allodynia and depressive-like behavior, and resulted in an increase in IL-1 beta gene expression in the frontal cortex and brain-derived neurotrophic factor (BDNF) gene expression in PAG. Treatment with metyrapone (MET), a corticosteroid synthesis inhibitor, before stress eliminated deleterious effects of chronic stress on SNI. Finally, this study showed that interference with IL-1 beta signaling, through administration of IL-1 receptor antagonist (IL-1ra), ameliorated the effects of neuropathic pain on depressive-like behavior. Taken together, these data suggest that peripheral nerve injury leads to increased cytokine expression in the brain, which in turn, contributes to the development of depressive-like behavior. Furthermore, stress can facilitate the development of depressive-like behavior after nerve injury by promoting IL-1 beta expression. Molecular Psychiatry (2010) 15, 404-414; doi: 10.1038/mp.2009.91; published online 22 September 2009
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