Long J B, Martinez-Arizala A, Petras J M, Holaday J W
Cent Nerv Syst Trauma. 1986 Fall;3(4):295-315. doi: 10.1089/cns.1986.3.295.
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.
基于阿片类拮抗剂可改善创伤性或缺血性脊髓损伤后的神经功能转归这一证据，内源性阿片类物质被认为与这些疾病的病理生理学有关。纳洛酮可改善猫创伤性脊髓损伤后的脊髓灌注和神经功能，随后还观察到其可改善兔缺血性脊髓损伤后的神经功能转归。使用对不同类型阿片受体具有不同选择性的多种阿片类拮抗剂，提示κ阿片受体参与了这两种脊髓损伤模型。此外，大鼠脊髓创伤与内源性κ激动剂强啡肽A浓度升高以及损伤部位κ阿片受体结合能力增强有关。此外，鞘内注射强啡肽A可在大鼠中诱发后肢和尾巴松弛。因此，有人提出内源性阿片类物质在脊髓损伤中的病理生理作用涉及强啡肽A与κ阿片受体的相互作用。然而，最近的实验揭示了鞘内注射强啡肽A在大鼠中的作用与内源性强啡肽A在猫和兔脊髓损伤中的假定作用之间存在差异。鞘内注射强啡肽A所致的麻痹不受阿片受体拮抗剂或TRH的影响，由非阿片类强啡肽A片段产生而非其他选择性κ阿片激动剂产生，且与非阿片介导的脊髓血流减少有关。此外，尽管有报道称大鼠脊髓创伤后内源性阿片类物质发生了变化，但与猫和兔不同，纳洛酮未能改善大鼠创伤性脊髓损伤后的神经功能转归。因此，脊髓损伤中涉及的特定内源性阿片类物质和阿片受体类型仍有待确定，而且在不同物种的不同脊髓损伤模型中似乎并不普遍。此外，强啡肽A可能通过非阿片作用参与大鼠的脊髓损伤机制。
