Zhou Wei, Mahajan Aman, Longhurst John C
Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H859-65. doi: 10.1152/ajpheart.00149.2009. Epub 2009 Jun 26.
The role of nociceptin and its spinal cord neural pathways in electroacupuncture (EA)-related inhibition of visceral excitatory reflexes is not clear. Nociceptin/orphanin FQ (N/OFQ) is an endogenous ligand for a G protein-coupled receptor, called the N/OFQ peptide (NOP) receptor, which has been found to be distributed in the spinal cord. The present study investigated the importance of this system in visceral-cardiovascular reflex modulation during EA. Cardiovascular pressor reflex responses were induced by gastric distension in Sprague-Dawley rats anesthetized by ketamine and xylazine. An intrathecal injection of nociceptin (10 nM) at T1-2 attenuated the pressor responses by 35%, similar to the influence of EA at P 5-6 (42% decrease). An intrathecal injection of the NOP antagonist, [N-Phe(1)]nociceptin(1-13) NH(2), partially reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not alter the EA-like inhibitory effect of nociceptin on the pressor reflex, whereas a combination of nociceptin receptor antagonist with naloxone completely abolished the EA response. An intrathecal injection of nociceptin attenuated the pressor responses to the electrical stimulation of the rostral ventrolateral medulla by 46%, suggesting that nociceptin can regulate sympathetic outflow. Furthermore, a bilateral microinjection of NOP antagonist into either the dorsal horn or the intermediolateral column at T1 partially reversed the EA inhibitory effect. These results suggest that nociceptin in the spinal cord mediates part of the EA-related modulation of visceral reflex responses.
痛敏肽及其脊髓神经通路在电针(EA)相关的内脏兴奋性反射抑制中的作用尚不清楚。痛敏肽/孤啡肽FQ(N/OFQ)是一种G蛋白偶联受体的内源性配体,称为N/OFQ肽(NOP)受体,已发现其分布于脊髓中。本研究调查了该系统在EA期间内脏-心血管反射调节中的重要性。在氯胺酮和赛拉嗪麻醉的Sprague-Dawley大鼠中,通过胃扩张诱导心血管升压反射反应。在T1-2节段鞘内注射痛敏肽(10 nM)使升压反应减弱35%,类似于在P 5-6节段电针的影响(降低42%)。鞘内注射NOP拮抗剂[N-Phe(1)]痛敏肽(1-13) NH(2)可部分逆转EA反应。用阿片受体拮抗剂纳洛酮预处理并未改变痛敏肽对升压反射的类EA样抑制作用,而痛敏肽受体拮抗剂与纳洛酮联合使用则完全消除了EA反应。鞘内注射痛敏肽使对延髓头端腹外侧电刺激的升压反应减弱46%,表明痛敏肽可调节交感神经输出。此外,在T1节段双侧向背角或中间外侧柱微量注射NOP拮抗剂可部分逆转EA的抑制作用。这些结果表明,脊髓中的痛敏肽介导了EA相关的内脏反射反应调节的一部分。