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Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats

Department of Medicine, Susan Samueli Center for Integrative Medicine, College of Medicine, University of California, Irvine, CA 92697-4075

Submitted 15 November 2004 ; accepted in final form 12 January 2005

Electroacupuncture (EA) at Neiguan-Jianshi acupoints through an opioid mechanism inhibits the cardiovascular pressor response induced by mechanical stimulation of the stomach. Because nociceptin also may regulate cardiovascular activity through its action in the brain stem, we hypothesized that this neuromodulator serves a role in the EA-related inhibitory effect. Blood pressure in ventilated male Sprague-Dawley rats (400–600 g) anesthetized by ketamine and -chloralose was measured during balloon inflation of the stomach. Gastric distension with 6–8 ml of air induced consistent pressor reflexes of 26 ± 1 mmHg that could be repeated every 10 min for 100 min. When nociceptin (10 nM) was microinjected into the rostral ventrolateral medulla (rVLM), the pressor response induced by gastric distension was inhibited by 68 ± 6%. Thirty minutes of EA also decreased the reflex response by 75 ± 11%; microinjection of saline into the rVLM did not alter the inhibitory effect of EA. In contrast, microinjection of a nociceptin receptor antagonist into the rVLM promptly reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not influence the EA-like inhibitory effect of nociceptin on the distension-induced pressor reflex (22 ± 1 to 8 ± 2 mmHg). Furthermore, a µ-opioid receptor agonist microinjected into the rVLM after microinjection of a nociceptin receptor antagonist during EA promptly reversed the nociceptin receptor antagonist-related inhibition of the EA effect. Thus, in addition to the classical opioid system, nociceptin, through opioid receptor-like-1 receptor stimulation in the rVLM, participates in the modulatory influence of EA on reflex-induced increases in blood pressure.

opioids; gastric distension; somatic afferent

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