Neuropeptides in spinal cord injury: comparative experimental models.
The possible role of endogenous opioids in the pathophysiology of spinal cord injury was evaluated utilizing a variety of experimental models and species. In the cat, we have shown that beta-endorphin-like immunoreactivity was increased in plasma following traumatic spinal injury; such injury was associated with a decrease in spinal cord blood flow (SCBF) which was reversed by the opiate receptor antagonist naloxone. Naloxone treatment also significantly improved functional neurological recovery after severe injury. Thyrotropin-releasing hormone (TRH), possibly through its "anti-endorphin" actions, was even more effective than naloxone in improving functional recovery in the cat. In a rat model, utilizing a similar trauma method, TRH proved superior to naloxone in improving SCBF after injury. In addition, naloxone at high doses attenuated the hindlimb paralysis produced by temporary aortic occlusion in the rabbit. The high doses of naloxone required to improve neurological function after spinal injury suggest that naloxone's actions, if opiate receptor mediated, may be mediated by non-mu receptors. Dynorphin, an endogenous opioid with a high affinity for the kappa receptor, produced hindlimb paralysis following intrathecal administration in rats. Taken together, these findings suggest that endogenous opioids, possibly acting at kappa receptors in the spinal cord, may serve as pathophysiological factors in spinal cord injury.
D000818:Animals; D002415:Cats; D004195:Disease Models, Animal; D004399:Dynorphins; D004723:Endorphins / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006614:Hindlimb / Q000294:innervation; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology; D010243:Paralysis / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000098:blood supply; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D004723:Endorphins; D009294:Narcotics; D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins