Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury.
Traumatic spinal cord injury (SCI) activates the hypothalamic-pituitary-adrenal (HPA) axis, a potent neuroendocrine regulator of stress and inflammation. SCI also elicits a profound and sustained intraspinal and systemic inflammatory response. Together, stress hormones and inflammatory mediators will affect the growth and survival of neural and non-neural cells and ultimately neurologic recovery after SCI. Glucocorticoids (GCs) are endogenous anti-inflammatory steroids that are synthesized in response to stress or injury, in part to regulate inflammation. Exogenous synthetic GCs are often used for similar purposes in various diseases; however, their safety and efficacy in pre-clinical and clinical SCI is controversial. The relatively recent discovery that macrophage migration inhibitory factor (MIF) is produced throughout the body and can override the anti-inflammatory effects of GCs may provide unique insight to the importance of endogenous and exogenous GCs after SCI. Here, we review both GCs and MIF and discuss the potential relevance of their interactions after SCI, especially their role in regulating maladaptive mechanisms of plasticity and repair that may contribute to the onset and maintenance of neuropathic pain.
Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
Jessica K
JK
Lerch
Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
Denise A
DA
Puga
Department of Physical Medicine and Rehabilitation and Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, The Feinstein Institute for Medical Research, NY, USA.
Ona
O
Bloom
Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA. Electronic address: popovich.2@osu.edu.
Phillip G
PG
Popovich
D000818:Animals; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009437:Neuralgia / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000378:metabolism; D025941:Protein Interaction Mapping; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D011965:Receptors, Glucocorticoid; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
Glucocorticoid; Inflammation; Macrophage migration inhibitory factor (MIF); Neuropathic pain; Spinal cord injury