Neurobiological Effects of Morphine after Spinal Cord Injury

Abstract

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.

Effects of astaxanthin on sensory‐motor function in a compression model of spinal cord injury: Involvement ofERKandAKTsignalling pathway

“…We herein showed that AST treatment significantly attenuates neural loss and demyelination at the lesion centre. It has been indicated that SCI‐induced histopathological damage is not restricted to the site of traumatic injury and extends both rostrally and caudally from the epicentre (Hook et al., ). Accordingly, in another study we showed that AST treatment protects spinal cord tissue at the rostral and caudal parts of clip compression injury, as well (Fakhri et al., ).…”

Pharmacological Management of Acute Spinal Cord Injury: A longitudinal multi-cohort observational study

“…5,6,8,9 Detrimental effects were also observed for some medications, including opioids, which attenuated the recovery of locomotor function and exacerbated pathophysiological processes in rodent models of spinal cord injury. 28,29 A detrimental opioid effect is in line with beneficial effects of naloxone (i.e., opioid antagonist), [30][31][32] and is highly concerning in light of the fact that opioids are ubiquitously administered for pain management in the early stages of injury (to > 80% of the patients). While completely removing or restricting opioids would be highly problematic and present with serious ethical concerns (i.e., weighing the management of acute pain with long-term neurological effects), opioids were among medications commonly administered to prevent the onset of pain.…”

Spinal Cord Injury in Rats Disrupts the Circadian System

“…As expected, rats with SCI showed a substantial deficit in hindlimb movement at 1 dpi, and the rats recovered frequent stepping by the chronic 42 dpi time point. Locomotor recovery had not previously been assessed in this model (a T8 150 kdyn contusion with 1 s dwell; Putatunda et al, 2014; Gaudet et al, 2017; Hook et al, 2017). Interestingly, the post-SCI locomotor recovery presented here complements the findings of others: our average BBB score of 10.6 in female 42 dpi rats supports that this injury severity is between the severities reported previously (vs 150 and 200 kdyn with 0 s dwell; Scheff et al, 2003).…”