Opioid and nonopioid mechanisms may contribute to dynorphin's pathophysiological actions in spinal cord injury.

Abstract

It has been suggested that the opioid dynorphin, an endogenous agonist for kappa-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 kappa-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 (kappa-receptor)-mediated and nonopioid mechanisms.

• Authors: A I Faden
• Journal: Annals of neurology (Ann Neurol) Vol. 27 Issue 1 Pg. 67-74 (Jan 1990) ISSN: 0364-5134 [Print] United States
• PMID: 1967925 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Opioid
• norbinaltorphimine
• Naltrexone
• Dynorphins

Topics

• Animals
• Dynorphins (administration & dosage, pharmacology)
• Injections, Spinal
• Male
• Naltrexone (administration & dosage, analogs & derivatives, pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Opioid (physiology)
• Spinal Cord Injuries (physiopathology)