GGrantIndex
← Search

Mechanims of CNS Autonomic Regulation by EA

$360,499R01FY2013HLNIH

University Of California-Irvine, Irvine CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Acupuncture and its potent alternative, electroacupuncture (EA), are accepted treatments for pain, nausea and vomiting. Small trails further suggest that EA can lower elevated blood pressure. Studies conducted in the last two grant cycles have evaluated supra-spinal mechanisms underlying EA's ability to reduce elevated sympathetic outflow and blood pressure. Acupuncture is differentiated from non-specific somatosympathetic stimulation by its relative point specificity and its prolonged action. We recently demonstrated point specific blood pressure modulation with the largest effect occurring during low frequency, low intensity EA at the pericardial and stomach meridians, specifically at P5-P6 and St36-St37, since these sets of acupoints provide significant input to premotor sympathetic neurons in the rostral ventrolateral medulla (rVLM). We also have demonstrated that opioids, specifically endorphins and enkephalin, nociceptin and (-amino butyric acid (GABA), mediate the initial EA-related inhibition while opioids and GABA underlie prolonged modulation of blood pressure by EA. EA works both pre- and post- synaptically on rVLM glutamate release, to lower sympathetic outflow. This renewal extends our studies to investigate EA segmental regulation of elevated blood pressure through actions involving dynorphin and nociceptin in the spinal cord dorsal horn and intermediolateral columns. In addition, we recently have begun to explore the potential for acupuncture to elevate depressed blood pressure in two models of reflex vasodepression. The first uses phenylbiguanide (PBG) in chloralose anesthetized cats to stimulate 5- hydroxytryptamine-3 (5-HT3) cardiopulmonary receptors to reflexly lower heart rate and blood pressure through pathways in the medial nucleus tractus solitarii (mNTS) and nucleus ambiguus (NA). The second involves reflex cardiovascular depression during mild gastric distension in ketamine-xylazine anesthetized rats, which appears to inhibit the prevagal neurons in the NA and presympathetic neurons in the rVLM through a GABAA mechanism, likely originating from the caudal ventrolateral medulla (cVLM). Preliminary data suggest that EA modulates these cardiodepressor reflexes through GABAergic, 5-HT or opioidergic mechanisms in the mNTS, nucleus raphe pallidus and NA during PBG stimulation and through GABA in the cVLM and NA during gastric distension. Additional studies, which have important clinical implications, will investigate stimulation modality and the underlying mechanisms, including point specificity, frequency modulation and spatial summation by combining two sets of acupoints. An improved understanding of acupuncture's ability to normalize blood pressure through its spinal and supraspinal actions, as well as underlying mechanisms, will provide important clues that can assist in the clinical use of acupuncture in conditions of either elevated or depressed blood pressure and will contribute to increased acceptance of this therapeutic technique by the western medical and scientific communities.

View original record on NIH RePORTER →