Intrathecal dynorphin-A infusion in rat spinal cord causes energy depletion, edema and neurologic dysfunction.
The opioid dynorphin-A (dynA) is thought to contribute to the secondary injury process following spinal cord trauma although little is known about the biochemical mechanisms involved. In the present study, we have used a combination of magnetic resonance imaging (MRI) and spectroscopy (MRS) and hindlimb motor function tests to examine the effects of intrathecal dynA infusion on rat spinal cord. Infusion of 100 nmol of dynA (1-17) caused pronounced edema development as determined by MRI at 24 h after infusion. Infusion of 100 nmol of the dynA (2-17) fragment, which does not have any activity at opiate receptors, also produced profound edema whereas 100 nmol of the low potency kappa opiate receptor ligand dynA (1-8) or artificial CSF (ACSF) did not produce any edema. Both dynA (1-17) and dynA (2-17) produced significant hindlimb motor deficits at 24 h when compared to dynA (1-8) and ACSF (P < 0.05), but the deficits in the dynA (1-17) group were significantly worse than in the dynA (2-17) treated animals (P < 0.05). Similarly, mortality in the dynA (1-17) treated animals was significantly higher than in the other groups (P = 0.002). Phosphorus MRS demonstrated that the dynA (1-17) and dynA (2-17) treated animals also had a pronounced decline in high energy phosphates in the spinal cord 24 h after infusion. We conclude that dynA contributes to spinal cord cell death by causing metabolic failure and edema development.
D000704:Analysis of Variance; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced*; D004734:Energy Metabolism / Q000187:drug effects*; D006614:Hindlimb / Q000294:innervation*; D007263:Infusions, Parenteral; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013118:Spinal Cord Diseases / Q000139:chemically induced*
D004399:Dynorphins