Tzabazis Alexander Z, Pirc Geanine, Votta-Velis Effrossyni, Wilson Steven P, Laurito Charles E, Yeomans David C
Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA.
Anesthesiology. 2007 Jun;106(6):1196-203. doi: 10.1097/01.anes.0000267603.32634.03.
Calcitonin gene-related peptide (CGRP) is contained in and released by small-diameter, nociceptive primary afferent sensory neurons. Upon spinal release, one of the effects of CGRP seems to be to sensitize dorsal horn neurons to subsequent input from nociceptive afferents and, consequently, to induce a behavioral hyperalgesia. Therefore, attenuating evoked release of CGRP from central terminals of nociceptors should have an antihyperalgesic effect.
The authors applied a recombinant herpes vector, encoding an antisense sequence to the whole CGRP gene, to the dorsal surface of the hind paw of mice to knock down expression of the peptide selectively in primary afferents innervating this tissue.
Herpes virus-based vector encoding an antisense sequence for the whole CGRP clearly reduced CGRP immunoreactivity in the infected spinal dorsal horn levels as well as in cultured dorsal root ganglia neurons. Selective knockdown of CGRP in primary afferents significantly attenuated the thermal, C-fiber hyperalgesia normally observed after topical application of capsaicin. The effect of viral vector-mediated knockdown of CGRP was comparable to the effect of intrathecal application of the CGRP antagonist CGRP8-37, but lasted for 14 weeks after one single application.
Viral vector-mediated knockdown of CGRP in primary afferent neurons provides a promising tool for treatment of chronic pain states as well as for studies investigating the pathophysiology underlying these conditions.
降钙素基因相关肽（CGRP）存在于小直径伤害性初级传入感觉神经元中并由其释放。在脊髓释放后，CGRP的作用之一似乎是使背角神经元对伤害性传入神经的后续输入敏感，从而诱导行为性痛觉过敏。因此，减弱伤害感受器中枢终末诱发的CGRP释放应具有抗痛觉过敏作用。
作者将一种编码针对整个CGRP基因反义序列的重组疱疹病毒载体应用于小鼠后爪的背表面，以选择性地敲低支配该组织的初级传入神经中该肽的表达。
编码针对整个CGRP反义序列的基于疱疹病毒的载体明显降低了感染的脊髓背角水平以及培养的背根神经节神经元中的CGRP免疫反应性。初级传入神经中CGRP的选择性敲低显著减轻了局部应用辣椒素后通常观察到的热、C纤维痛觉过敏。病毒载体介导的CGRP敲低效果与鞘内应用CGRP拮抗剂CGRP8-37的效果相当，但单次应用后可持续14周。
病毒载体介导的初级传入神经元中CGRP的敲低为慢性疼痛状态的治疗以及研究这些病症背后的病理生理学提供了一种有前景的工具。
