Khasar S G, Gold M S, Dastmalchi S, Levine J D
Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Neurosci Lett. 1996 Oct 25;218(1):17-20. doi: 10.1016/0304-3940(96)13111-6.
To test the hypothesis that the expression of specific proteins on peripheral terminals of primary afferents can be attenuated by intrathecal administration of antisense oligodeoxynucleotides (ODNs), we administered ODNs antisense to the mu-opioid receptor to male Sprague-Dawley rats via chronically implanted intrathecal cannulae. Antisense but not mismatch ODN treatment significantly decreased peripheral (D-Ala2, N-Me-Phe4, Gly5-ol)-enkephalin (DAMGO) inhibition of prostaglandin E2 (PGE2) hyperalgesia. Antisense treatment affected neither the magnitude of PGE2 hyperalgesia nor the antinociception produced by a peripherally administered adenosine A1-agonist. The antinociceptive effects of DAMGO was fully recovered 8 days after cessation of ODN treatment. DAMGO-induced inhibition of voltage-gated Ca2+ currents (VGCC), in cultured dorsal root ganglion (DRG) neurons from rats treated with ODNs, was also significantly reduced by antisense but not mismatch ODNs. Taken together, these observations suggest that intrathecal administration of antisense ODNs can be used to study the function of proteins present in the peripheral terminals of primary afferent neurons.
为了验证鞘内注射反义寡脱氧核苷酸（ODN）可使初级传入神经外周终末特定蛋白的表达减弱这一假说，我们通过长期植入的鞘内套管，将针对μ-阿片受体的反义ODN注射到雄性Sprague-Dawley大鼠体内。反义而非错配ODN处理显著降低了外周（D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-醇）-脑啡肽（DAMGO）对前列腺素E2（PGE2）痛觉过敏的抑制作用。反义处理既不影响PGE2痛觉过敏的程度，也不影响外周给予腺苷A1激动剂所产生的镇痛作用。在停止ODN处理8天后，DAMGO的镇痛作用完全恢复。在用ODN处理的大鼠的培养背根神经节（DRG）神经元中，反义而非错配ODN也显著降低了DAMGO诱导的电压门控Ca2+电流（VGCC）的抑制作用。综上所述，这些观察结果表明，鞘内注射反义ODN可用于研究初级传入神经元外周终末中存在的蛋白的功能。
