Suzuki Takahiro, Li Yong Hua, Mashimo Takashi
Department of Anesthesiology, Osaka University Medical School, Osaka, Japan.
Anesth Analg. 2005 Sep;101(3):793-799. doi: 10.1213/01.ANE.0000160582.25368.B9.
Although Neurotropin(R) (NTP) has been used clinically as an analgesic in Japan for many years, its effect on neuropathic pain in animal models has not been examined in detail. Its main effect has been indicated to be activation of the descending monoaminergic pain inhibitory systems. To study the effect of NTP on neuropathic pain, we subjected mice to spinal nerve ligation. NTP inhibited both tactile allodynia and mechanical and thermal hyperalgesia in a dose-dependent manner. When the effect of NTP was examined after depletion of monoamines in the spinal cord by intrathecal neurotoxins, the antiallodynic and antihyperalgesic effects were still observed after serotonergic denervation, but not after noradrenergic denervation. In addition, intracerebroventricular NTP increased withdrawal threshold and latency although intrathecal or local administration of NTP did not. These results suggest that the antiallodynic and antihyperalgesic effect of NTP on neuropathic pain induced by spinal nerve ligation is mediated principally through the action at supraspinal sites and through activation of spinal noradrenergic systems, possibly via the descending inhibitory pathway.
尽管神经妥乐平(Neurotropin®,NTP)在日本已作为镇痛药临床使用多年,但其对动物模型中神经性疼痛的影响尚未得到详细研究。其主要作用被认为是激活下行单胺能疼痛抑制系统。为了研究NTP对神经性疼痛的影响,我们对小鼠进行了脊神经结扎。NTP以剂量依赖性方式抑制触觉异常性疼痛以及机械性和热痛觉过敏。当通过鞘内注射神经毒素耗尽脊髓中的单胺后检测NTP的作用时,在5-羟色胺能去神经支配后仍观察到抗异常性疼痛和抗痛觉过敏作用,但在去甲肾上腺素能去神经支配后则未观察到。此外,脑室内注射NTP可提高撤药阈值和潜伏期,而鞘内或局部注射NTP则不能。这些结果表明,NTP对脊神经结扎诱导的神经性疼痛的抗异常性疼痛和抗痛觉过敏作用主要通过在脊髓上部位的作用以及通过激活脊髓去甲肾上腺素能系统介导,可能是通过下行抑制途径。