Table 1.

This table summarizes both the beneficial and adverse consequences of opioid administration in the Acute (D1–7) and Chronic (D7+) phases of spinal cord injury. In both phases, opioid administration results in pain relief. However, this pain relief is accompanied by numerous consequences.

Consequence of SCI or Opioid Administration	Mechanisms Common to SCI and Opioid Administration
Decreased locomotor function	Excitotoxic cell death	Increased extracellular glutamate
		Increased NMDAR activation
		Increased dynorphin levels
	Increased glial activation	Release glutamate, ATP, CGRP, pro-inflammatory cytokines, ROS, NO
	Apoptosis	Initiated via activation of caspase-3, increased Bax and decreased Bcl-2 Causes release of pro-inflammatory cytokines
Pain development	Central sensitization	Increased NMDAR activation
		Increased extracellular glutamate
	OIH	Increased NMDAR activation
		Increased glutamate availability
		Increased spinal dynorphin
	Increased glial activation	Release glutamate, ATP, CGRP, pro-inflammatory cytokines, ROS, NO, activation of MAPK pathways, TLR’s
Increased risk of infection	Immune suppression, HPA dysregulation	Decreased lymphocyte levels
Mortality	Increased glial activation	Increased pro-inflammatory cytokines