Motor dysfunction after spinal cord injury is mediated by opiate receptors

Naloxone, an opiate receptor antagonist, improves neurological outcome following traumatic cervical spinal cord injury in the cat and ischemic lumbar spinal cord injury in the rabbit. However, the doses of naloxone required have been quite high (greater than 1 mg/kg), suggesting that its beneficial actions are either not opiate receptor mediated or mediated by non-mu opiate receptors (which are less naloxone-sensitive). The kappa receptor appears to be the predominant opiate receptor in the spinal cord in a variety of species. For these reasons we evaluated the effects of a somewhat kappa selective opiate receptor antagonist WIN44,441-3 [WIN(-)] on neurological recovery following traumatic spinal injury in the cat and ischemic spinal injury in the rabbit. Animals treated with this more selective antagonist showed improved motor recovery as compared with animals treated with either physiological saline or with the dextroisomer of the WIN compound [WIN44,441-2; WIN(+)]. These findings support the hypothesis that motor dysfunction after spinal cord injury is in part mediated by opiate receptors and indicate that kappa selective opiate receptor antagonists may have particular therapeutic utility in spinal cord injury.