Opioids and non-steroidal anti-inflammatory drugs are used commonly to manage
pain in the early phase of
spinal cord injury (SCI). Despite its
analgesic efficacy, however, our studies suggest that intrathecal
morphine undermines locomotor recovery and increases lesion size in a rodent model of SCI. Similarly, intravenous (IV)
morphine attenuates locomotor recovery. The current study explores whether IV
morphine also increases lesion size after a spinal
contusion (T12) injury and quantifies the cell types that are affected by early
opioid administration. Using an experimenter-administered escalating dose of IV
morphine across the first seven days post-injury, we quantified the expression of neuron, astrocyte, and microglial markers at the injury site. SCI decreased NeuN expression relative to shams. In subjects with SCI treated with IV
morphine, virtually no NeuN+ cells remained across the rostral-caudal extent of the lesion. Further, whereas SCI per se increased the expression of astrocyte and microglial markers (
glial fibrillary acidic protein and OX-42, respectively),
morphine treatment decreased the expression of these markers. These cellular changes were accompanied by attenuation of locomotor recovery (Basso, Beattie, Bresnahan scores), decreased
weight gain, and the development of
opioid-induced
hyperalgesia (increased tactile reactivity) in
morphine-treated subjects. These data suggest that
morphine use is contraindicated in the acute phase of a
spinal injury. Faced with a lifetime of
intractable pain, however, simply removing any effective
analgesic for the management of SCI
pain is not an ideal option. Instead, these data underscore the critical need for further understanding of the molecular pathways engaged by conventional medications within the pathophysiological context of an injury.