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Stress and IL-1β contribute to the development of depressive-like behavior following peripheral nerve injury

Molecular Psychiatry volume 15, pages 404–414 (2010)Cite this article

Abstract

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-1β (IL-1β) 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-1β 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-1β 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-1β expression.

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Acknowledgements

We thank ZM Weil for technical support and assistance with data analysis. This work was supported by grants from the American Heart Association (predoctoral fellowship to KK), National Institute of Neurological Disorders and Stroke Behavioral Core Grant P30 NS045758 (to ACD), 5R01NR010806 SNI Grant (to ACD).

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Authors and Affiliations

  1. Department of Psychology, The Ohio State University, Columbus, OH, USA

    G J Norman, N Zhang, J C Walton, J S Morris & A C DeVries

  2. Department of Neurosciences, The Ohio State University, Columbus, OH, USA

    K Karelina, J C Walton & A C DeVries

  3. The Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA

    A C DeVries

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  1. G J Norman
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  2. K Karelina
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Correspondence to G J Norman.

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Norman, G., Karelina, K., Zhang, N. et al. Stress and IL-1β contribute to the development of depressive-like behavior following peripheral nerve injury. Mol Psychiatry 15, 404–414 (2010). https://doi.org/10.1038/mp.2009.91

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