Wiesenfeld-Hallin Z, Xu X J, Langel U, Bedecs K, Hökfelt T, Bartfai T
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3334-7. doi: 10.1073/pnas.89.8.3334.
The endogenous inhibitory role of the neuropeptide galanin in pain transmission and spinal cord excitability was demonstrated by the use of a high-affinity galanin receptor antagonist, M-35 [galanin-(1-13)-bradykinin-(2-9)-amide]. M-35, which displaced 125I-labeled galanin from membranes of rat dorsal spinal cord with an IC50 of 0.3 nM, dose-dependently antagonized the effect of intrathecal galanin on the flexor reflex. M-35 potentiated the facilitation of the flexor reflex by conditioning stimulation of cutaneous unmyelinated afferents in rats with intact nerves and the potentiating effect of M-35 on the conditioning-stimulation-induced reflex facilitation of the cutaneous unmyelinated afferents was strongly enhanced after axotomy. These results demonstrate that endogenous galanin plays a tonic inhibitory role in the mediation of spinal cord excitability, and it is particularly noteworthy that this function of galanin is remarkably enhanced after peripheral nerve section.
通过使用高亲和力的甘丙肽受体拮抗剂M-35 [甘丙肽-(1-13)-缓激肽-(2-9)-酰胺],证实了神经肽甘丙肽在疼痛传递和脊髓兴奋性方面的内源性抑制作用。M-35能以0.3 nM的IC50从大鼠背侧脊髓膜上置换出125I标记的甘丙肽,它能剂量依赖性地拮抗鞘内注射甘丙肽对屈肌反射的作用。在完整神经的大鼠中,M-35通过对皮肤无髓传入纤维进行条件刺激来增强屈肌反射,并且在轴突切断后,M-35对条件刺激诱导的皮肤无髓传入纤维反射增强的作用显著增强。这些结果表明,内源性甘丙肽在脊髓兴奋性的介导中起紧张性抑制作用,特别值得注意的是,在周围神经切断后,甘丙肽的这一功能显著增强。