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 secondar y injury process following spinal cord trauma although little is known about the biochemical mechanisms involved. In the present study, we h ave used a combination of magnetic resonance imaging (MRI) and spectro scopy (MRS) and hindlimb motor function tests to examine the effects o f intrathecal dynA infusion on rat spinal cord. Infusion of 100 nmol o f 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) fragm ent, which does not have any activity at opiate receptors, also produc ed profound edema whereas 100 nmol of the low potency re opiate recept or ligand dynA (1-8) or artificial CSF (ACSF) did not produce any edem a. Both dynA (1-17) and dynA (2-17) produced significant hindlimb moto r deficits at 24 h when compared to dynA (1-8) and ACSF (P < 0.05), bu t 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 conc lude that dynA contributes to spinal cord cell death by causing metabo lic failure and edema development.