Based upon evidence that
opioid antagonists improve neurological outcome following either traumatic or ischemic
spinal cord injury, endogenous
opioids have been implicated in the pathophysiology of these disorders.
Naloxone improved both spinal cord perfusion and neurological function following traumatic
spinal cord injury in cats, and was subsequently observed to improve neurological outcome following ischemic
spinal cord injury in rabbits. Using several
opioid antagonists with varied selectivities for different types of
opioid receptors, it was suggested that
kappa opioid receptors are involved in both these models of
spinal cord injury. In addition,
spinal cord trauma in rats is associated with increased concentrations of the endogenous kappa agonist
dynorphin A, and increased
kappa opioid receptor binding capacity localized to the injury site. Furthermore,
dynorphin A induces hindlimb and tail flaccidity following
intrathecal injection in rats. Thus, the pathophysiological effects of endogenous
opioids in
spinal cord injury have been proposed to involve
dynorphin A interactions with
kappa opioid receptors. However, disparities between the actions of intrathecally injected
dynorphin A in rats and the presumed actions of endogenous
dynorphin A in cat and rabbit
spinal cord injury have been revealed in recent experiments.
Paralysis resulting from intrathecal
dynorphin A is not altered by
opioid receptor antagonists or TRH, produced by non-
opioid dynorphin A fragments but not by other selective kappa
opioid agonists, and associated with non-
opioid mediated reductions in spinal cord blood flow. Furthermore, despite reports of endogenous
opioid changes following rat
spinal cord trauma, in contrast to cats and rabbits,
naloxone failed to improve neurological outcome following traumatic rat
spinal cord injury. Thus, the specific endogenous
opioids and
opioid receptor types involved in
spinal cord injury remain to be resolved, and do not appear to be universal among different models of
spinal cord injury in different species. Additionally,
dynorphin A may participate in
spinal cord injury mechanisms in the rat through non-
opioid actions.