The role of angiotensin II in nociceptive transmission in the spinal cord

尽管脊髓是痛觉调节的重要区域，但脊髓血管紧张素II （AngII）在痛觉传递中的作用尚不清楚。因此，为了阐明AngII在脊髓伤害传递中的作用，我们研究了鞘内注射AngII对小鼠的影响。注射AngII后产生的行为反应包括抓挠、咬和舔。腹腔注射吗啡可剂量依赖性地抑制AngII诱导的行为，提示其行为反应与伤害感受有关。同时服用氯沙坦（一种AngII型1 （AT1）受体拮抗剂）和SB203580（一种p38 MAPK抑制剂）也能剂量依赖性地抑制伤害性行为。然而，at2受体拮抗剂pd123319、ERK1/2磷酸化上游抑制剂U0126和JNK抑制剂sp600125对Ang ii诱导的伤害性行为没有影响。Western blot分析显示，静脉注射AngII可诱导腰背脊髓p38 MAPK磷酸化，氯沙坦可抑制该磷酸化，但不影响ERK1/2和JNK。我们的数据表明，通过at1受体介导的p38 MAPK信号的激活诱导了AngII的伤害性行为。这一观察结果表明，AngII可能作为一种神经递质和/或神经调节剂在伤害性信息的脊髓传递中起作用。

Though the spinal cord is an important area for the modulation of nociception, the role of spinal angiotensin II (AngII) in nociceptive transmission remains unclear. Therefore, in order to elucidate the role of Ang II in nociceptive transmission in the spinal cord, we examined the effect of intrathecal (i.t.) administration of AngII into mice. I.t. administration of AngII produced a behavioral response consisting of scratching, biting and licking. The behavior induced by AngII was dose-dependently inhibited by intraperitoneal injection of morphine, suggesting that the behavioral response is related to nociception. The nociceptive behavior was also inhibited dose-dependently by i.t. co-administration of losartan, an AngII type 1 (AT1) receptor antagonist, and SB203580, a p38 MAPK inhibitor. However, AT2receptor antagonistPD123319, the upstream inhibitor of ERK1/2 phosphorylation U0126, and the JNK inhibitorSP600125 had no effect on Ang II-induced nociceptive behavior. Western blot analysis showed that the i.t. injection of AngII induced phosphorylation of p38 MAPK in the lumbar dorsal spinal cord, which was inhibited by losartan, without affecting ERK1/2 and JNK.Our data show that i.t. administration of AngII induces nociceptive behavior accompanied by the activation of p38 MAPK signaling mediated through AT1receptors. This observation indicates that AngII may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information.