Department of Pharmacology, Faculty of Medicine of Ribeirão Preto-USP, Avenida Bandeirantes 3900, Ribeirão Preto, SP, Brazil.
J Pain. 2011 Jan;12(1):51-60. doi: 10.1016/j.jpain.2010.04.008. Epub 2010 Jun 16.
We evaluated the effectiveness of intrathecal antagonists of α1- (WB4101) and α2- (idazoxan) adrenoceptors and serotonergic (methysergide), opioid (naloxone), muscarinic (atropine), GABA(A) (bicuculline) and GABA(B) (phaclofen) receptors in blocking 2- or 100-Hz electroacupuncture (EA)-induced analgesia (EAIA) in the rat tail-flick test. EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints in lightly anesthetized rats. EA increased tail-flick latency, where the effect of 2-Hz EA lasted longer than that produced by 100-Hz EA. The 2-Hz EAIA was inhibited by naloxone or atropine, was less intense and shorter after WB4101 or idazoxan, and was shorter after methysergide, bicuculline, or phaclofen. The 100-Hz EAIA was less intense and shorter after naloxone and atropine, less intense and longer after phaclofen, shorter after methysergide or bicuculline, and remained unchanged after WB4101 or idazoxan. We postulate that the intensity of the effect of 2-Hz EA depends on noradrenergic descending mechanisms and involves spinal opioid and muscarinic mechanisms, whereas the duration of the effect depends on both noradrenergic and serotonergic descending mechanisms, and involves spinal GABAergic modulation. In contrast, the intensity of 100-Hz EAIA involves spinal muscarinic, opioid, and GABA(B) mechanisms, while the duration of the effects depends on spinal serotonergic, muscarinic, opioid, and GABA(A) mechanisms.
The results of this study indicate that 2- and 100-Hz EA induce analgesia in the rat tail-flick test activating different descending mechanisms at the spinal cord level that control the intensity and duration of the effect. The adequate pharmacological manipulation of such mechanisms may improve EA effectiveness for pain management.
我们评估了鞘内 α1-(WB4101)和 α2-(伊索唑兰)肾上腺素能受体以及 5-羟色胺能(美西麦角)、阿片能(纳洛酮)、毒蕈碱能(阿托品)、GABA(A)(荷包牡丹碱)和 GABA(B)(phaclofen)受体拮抗剂在阻断大鼠尾部闪烁测试中 2 或 100-Hz 电针(EA)诱导的镇痛(EAIA)中的作用。在轻度麻醉的大鼠中,双侧应用 EA 于足三里和三阴交穴位。EA 增加尾部闪烁潜伏期,其中 2-Hz EA 的作用持续时间长于 100-Hz EA。2-Hz EAIA 被纳洛酮或阿托品抑制,在 WB4101 或伊索唑兰后强度较低且持续时间较短,在美西麦角、荷包牡丹碱或 phaclofen 后持续时间较短。100-Hz EAIA 在纳洛酮和阿托品后强度较低且持续时间较短,在 phaclofen 后强度较低且持续时间较长,在美西麦角或荷包牡丹碱后持续时间较短,在 WB4101 或伊索唑兰后无变化。我们推测,2-Hz EA 的作用强度取决于去甲肾上腺素能下行机制,并涉及脊髓阿片能和毒蕈碱机制,而作用持续时间取决于去甲肾上腺素能和 5-羟色胺能下行机制,并涉及脊髓 GABA 能调制。相比之下,100-Hz EAIA 涉及脊髓毒蕈碱、阿片能和 GABA(B)机制,而效应的持续时间取决于脊髓 5-羟色胺能、毒蕈碱、阿片能和 GABA(A)机制。
本研究结果表明,2-和 100-Hz EA 在大鼠尾部闪烁测试中诱导镇痛,激活脊髓水平不同的下行机制,控制效应的强度和持续时间。对这些机制进行适当的药理学处理可能会提高 EA 在疼痛管理中的效果。