OPIOID AND NONOPIOID MECHANISMS MAY CONTRIBUTE TO DYNORPHINS PATHOPHYSIOLOGICAL ACTIONS IN SPINAL-CORD INJURY

It has been suggested that the opioid dynorphin, an endogenous agonist for k‐opiate receptors, contributes to secondary tissue damage after spinal cord injury. To evaluate this hypothesis further, effects of intrathecally administered dynorphin (Dyn) A‐(1‐17), dynorphin antiserum, or the k‐selective opiate antagonist nor‐binaltorphimine (nor‐BNI) were studied in rats subjected to standardized impact trauma to the thoracic spinal cord. Effects of intrathecal Dyn A‐(1–17) were also compared to those of Dyn A‐(2–17), which is inactive at opiate receptors, in uninjured and injured animals. Both Dyn A‐(1–17) and Dyn A‐(2‐17) produced motor dysfunction in uninjured rats, but Dyn A‐(1–17) was approximately 2.5 times more potent. At lower doses of Dyn A‐(1–17), paraparesis was markedly attenuated by nor BNI; nor‐BNI was less effective at higher doses of Dyn A‐(1–17) and did not modify the motor dysfunction produced by Dyn A‐(2–17). Treatment with dynorphin antiserum significantly improved outcome after trauma as compared to control treatment with normal rabbit serum or leucine‐enkephalin antiserum. Dyn A‐(1–17), but not Dyn A‐(2–17) at similar doses, exacerbated neurological dysfunction after spinal cord injury. Pretreatment with nor‐BNI attenuated neurological dysfunction after traumatic spinal cord injury to a similar degree in rats administered saline or Dyn A‐(1–17). These observations support the hypothesis that dynorphin contributes to certain pathophysiological changes after traumatic spinal cord injury through both opiate‐receptor (k‐receptor)–mediated and nonopioid mechanisms. Copyright © 1990 American Neurological Association