Spinal nociceptin mediates electroacupuncture-related modulation of visceral sympathoexcitatory reflex responses in rats

Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
AJP Heart and Circulatory Physiology (Impact Factor: 3.84). 07/2009; 297(2):H859-65. DOI: 10.1152/ajpheart.00149.2009
Source: PubMed


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.

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    • "Ongoing studies are examining the optimal duration of acupuncture stimulation. Typically, changes in blood pressure, if they occur, begin after 10–15 min of stimulation (Li, Tjen-A-Looi, Guo, et al., 2010; Moazzami et al., 2010; Zhou et al., 2009), and 30–40 min seems to yield significant decreases or increases in blood pressure (Li, Tjen-A-Looi, Guo, et al., 2010; Tjen-A-Looi et al., 2004, 2006, 2009). However, it is not known if longer stimulations would be more effective. "
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    ABSTRACT: Although mechanisms underlying acupuncture regulation of pain have been studied by a number of laboratories in many countries, much less is known about its ability to modulate cardiovascular function. In the last two decades, our laboratory has systematically investigated the peripheral and central neural mechanisms underlying acupuncture regulation of blood pressure. These observations account for acupuncture's distant actions and, to some extent, its local actions, with respect to the site of needling. Four fundamental findings have advanced our knowledge. First, point-specific effects of acupuncture underlie its cardiovascular actions. Second, variable regions in the supraspinal and spinal central nervous system that receive input from somatic afferent stimulation account for acupuncture's ability to modulate blood pressure. Thus, depending on the underlying situation, for example, high or low blood pressure, acupuncture modifies autonomic outflow by reducing activity in brain stem nuclei that participate in the primary response. Third, repetitive acupuncture through a molecular mechanism can cause prolonged cardiovascular effects that far outlast acupuncture stimulation. Fourth, there is a range of cardiovascular responsiveness to acupuncture that depends, at least in part, on interactions between neural modulators that synaptically regulate autonomic function in the brain stem. Thus, acupuncture has the capability of profoundly regulating cardiovascular function in patients with disease, for example, hypertension, and the experimental laboratory is directing best approaches to study its actions in humans.
    International Review of Neurobiology 11/2013; 111:257-71. DOI:10.1016/B978-0-12-411545-3.00013-4 · 1.92 Impact Factor
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    • "A report by Fusumada et al. suggested that the periaqueductal gray (PAG) neurons activated by EA at ST36 might play an important role in the descending pain control system involving gamma aminobutyric acid (GABA), since the PAG has special reference to the SDH and function of pain control [28]. A bilateral microinjection of nociceptin receptor (NOP) antagonist into either the dorsal horn or the intermediolateral column at T1 partially reversed the inhibitory effect of EA at ST36, which suggests that nociceptin in the spinal cord mediates a part of the EA-related modulation of visceral reflex responses [29]. EA at ST36 could extensively regulate the information processing of SDH and induce the modulation of genes/expressed sequence tags (ESTs) in the same direction, which was correlated with neural signal transmission [30]. "
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    ABSTRACT: The aim of this study was to observe the effect of electroacupuncture (EA) at the ST36 acupoint on the firing rate of gastric-related neurons in the spinal dorsal horn (SDH) and nucleus tractus solitarius (NTS). There were different effects of gastric distention in SDH and NTS in 46 male Sprague-Dawley rats. In 10 excitatory neurons in SDH, most of the neurons were inhibited by homolateral EA. The firing rates decreased significantly (P < 0.05) in 10 excitatory gastric-related neurons in NTS; the firing rates of 6 neurons were further excited by homolateral EA, with a significant increase of the firing rates (P < 0.05); all inhibitory gastric-related neurons in NTS were excited by EA. The inhibition rate of homolateral EA was significantly increased in comparison with contralateral EA in gastric-related neurons of SDH (P < 0.05). There was no significant difference between homolateral and contralateral EA in gastric-related neurons of NTS. EA at ST36 changes the firing rate of gastric-related neurons in SDH and NTS. However, there are some differences in responsive mode in these neurons. The existence of these differences could be one of the physiological foundations of diversity and complexity in EA effects.
    Evidence-based Complementary and Alternative Medicine 09/2013; 2013:912898. DOI:10.1155/2013/912898 · 1.88 Impact Factor

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