title: 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.
authors.affiliation: 1 Texas A&M University Institute for Neuroscience, Texas A&M University , College Station, Texas.|2 Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center , Bryan, Texas.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hook
authors.affiliation: 3 Department of Anesthesiology, University of California , San Diego, California.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Woller
authors.affiliation: 2 Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center , Bryan, Texas.
authors.forename: Eric
authors.initials: E
authors.lastname: Bancroft
authors.affiliation: 1 Texas A&M University Institute for Neuroscience, Texas A&M University , College Station, Texas.|2 Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center , Bryan, Texas.
authors.forename: Miriam
authors.initials: M
authors.lastname: Aceves
authors.affiliation: 2 Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center , Bryan, Texas.
authors.forename: Mary Katherine
authors.initials: MK
authors.lastname: Funk
authors.affiliation: 2 Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center , Bryan, Texas.
authors.forename: John
authors.initials: J
authors.lastname: Hartman
authors.affiliation: 4 Department of Physiology, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Garraway
mesh_terms: D061605:Administration, Intravenous; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: cell death; hyperalgesia; locomotor recovery; opioid-induced; opioids; spinal cord injury