Ren K, Randich A, Gebhart G F
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Brain Res. 1988 Apr 19;446(2):285-94. doi: 10.1016/0006-8993(88)90887-6.
Modulation of the spinal nociceptive tail flick (TF) reflex by electrical stimulation of subdiaphragmatic or cervical vagal afferent fibers was characterized in rats lightly anesthetized with pentobarbital. Cervical vagal afferent stimulation (VAS) inhibited the TF reflex in a pulse width-, frequency-, and intensity-dependent fashion. The optimum parameters for inhibition of the TF reflex were determined to be 2.0 ms pulse width, 20 Hz frequency with a threshold (T) current of 60 microA. Cervical VAS at 0.2-0.6 T facilitated the TF reflex. Cervical VAS at T typically produced a depressor arterial blood pressure response, but inhibition of the TF reflex by VAS was not due to changes in blood pressure. Subdiaphragmatic VAS also inhibited the TF reflex and generally produced a pressor effect, but did not facilitate the TF reflex at intensities of stimulation less than T as did cervical VAS. The parameters of cervical VAS required for inhibition of TF reflex suggest that excitation of high-threshold, unmyelinated fibers are important in VAS-induced descending inhibition. The intrathecal administration of pharmacologic receptor antagonists into the subarachnoid space of the lumbar enlargement indicated that the opioid receptor antagonist naloxone produced a dose-dependent antagonism of cervical VAS-produced inhibition of TF reflex, but single doses of either phentolamine or methysergide (30 micrograms each) failed to affect the inhibition by VAS. Combined intrathecal injection of both phentolamine and methysergide (30 micrograms each), however, significantly attenuated inhibition of the TF reflex by cervical VAS. These results suggest that cervical VAS engages a spinal opioid system and co-activates descending serotonergic and noradrenergic systems to modulate spinal nociceptive processing.
在戊巴比妥轻度麻醉的大鼠中，研究了电刺激膈下或颈迷走传入纤维对脊髓伤害性甩尾（TF）反射的调制作用。颈迷走传入刺激（VAS）以脉冲宽度、频率和强度依赖的方式抑制TF反射。抑制TF反射的最佳参数确定为脉冲宽度2.0毫秒、频率20赫兹，阈值（T）电流为60微安。0.2 - 0.6T的颈VAS促进TF反射。T强度的颈VAS通常会引起动脉血压下降反应，但VAS对TF反射的抑制并非由血压变化所致。膈下VAS也抑制TF反射，且通常产生升压作用，但在刺激强度小于T时，不像颈VAS那样促进TF反射。抑制TF反射所需的颈VAS参数表明，高阈值无髓纤维的兴奋在VAS诱导的下行抑制中起重要作用。向腰膨大蛛网膜下腔鞘内注射药理受体拮抗剂表明，阿片受体拮抗剂纳洛酮对颈VAS产生的TF反射抑制具有剂量依赖性拮抗作用，但单剂量的酚妥拉明或麦角新碱（各30微克）均未能影响VAS的抑制作用。然而，鞘内联合注射酚妥拉明和麦角新碱（各30微克）可显著减弱颈VAS对TF反射的抑制作用。这些结果表明，颈VAS激活了脊髓阿片系统，并共同激活下行5-羟色胺能和去甲肾上腺素能系统，以调节脊髓伤害性信息处理。
