Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury

• Stress hormones and inflammatory mediators affect functional recovery after spinal cord injury.
• After spinal cord injury the hypothalamic–pituitary–adrenal (HPA) axis is dysregulated and circulating levels of GCs and MIF significantly increase.
• Aberrant downstream GC and MIF signaling mechanisms lead to chronic neurologic dysfunction.

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.