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Reduction of Blood Pressure by Electro Acupuncture in Mild to Moderate Hypertensive Patients: Randomized Controlled Trial
Stephanie C Tjen-A-Looi*
University of California School of Medicine, Irvine, CA 92697, USA
Stephanie C Tjen-A-Looi
University of California School of Medicine
Irvine, CA 92697, USA.
Received date: December 06, 2016; Accepted date: December 09, 2016; Published date: December 16, 2016
Citation: Tjen-A-Looi SC. Reduction of Blood Pressure by Electro Acupuncture in Mild to Moderate Hypertensive Patients: Randomized Controlled Trial. J Intensive& Crit Care 2017, 3:1.
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There is a growing interest in integrative medical treatments such as acupuncture on hypertension although therapy to control high blood pressure (BP) is available. We have demonstrated in a series of experimental investigations the mechanisms and actions of acupuncture and electro acupuncture (EA) in models of elevated BP associated with reflex induced sympathoexcitation [1-4]. These studies suggest that bilateral EA at select acupoints PC5- 6 and ST36-37, in contrast to EA at LI6-7 and GB37-39, inhibits sympathetically-mediated reflex responses lowering BP through cardiovascular regions in the brain and specific neurotransmitter systems. The experimental findings provided guidance in designing the clinical study to proof the overall hypothesis that weekly EA at PC5-6+ST36-37 but not LI6-7+GB37-39 acupoints for 8 weeks decreases BP for a prolonged period of time in patients with mild to moderate hypertension. We have used 24 h ambulatory blood pressure measurements to monitor EAinhibition of peak and average systolic and diastolic BP (SBP and DBP) and to identify high and low responders to EA. In a cross-over and double blinded design, we have shown that EA application to acupoints PC5-6+ST36-37 for 8 weeks reduces peak and average SBP by 8 and 6 mm Hg in the overall group. Of interest, in high responders EA decreases peak and average SBP by 16 and 11 mm Hg. Following 8 weeks of EA treatment, sympathetic activity reduces and therefore ultimately norepinephrine, reninaldosterone- system. In a subgroup of patients, we observed a long-lasting blood pressure lowering acupuncture effect for at least an additional four weeks after the end of EA treatment.
What is new?
Electro acupuncture at two sets of standardized acupoints known to provide input to brain stem regions that regulate sympathetic outflow lowers blood pressure in patients with mild hypertension who are not on antihypertensive therapy [5,6]. The blood pressure response is point specific since stimulation of another set of acupoints known to provide little input to cardiovascular regions in the medulla do not alter blood pressure. The blood pressure lowering response occurs over a 4-6 weeks when acupuncture is applied once weekly for 30 min using low frequency and low intensity [7,8]. Approximately 70% of patients, called high responders, who demonstrate larger responses to acupuncture, show persistent lowering of blood pressure for a month following an eight week course of therapy. Continued reinforcement treatment in the latter group once monthly maintains the acupuncture-related hypotensive effect for at least six months.
• Electro acupuncture applied once weekly for 30 min for 8 weeks lowers blood pressure in patients with mild to moderate hypertension who are off antihypertensive medications.
• The onset of the blood pressure lowering response occurs by the second week of the therapy and the decrease in blood pressure is observed over 4 to 6 weeks of acupuncture with a prolonged action, lasting for at least one month after the treatment.
• Reinforcement once monthly maintains a persistent low blood pressure.
What is relevant?
Electro acupuncture lowers blood pressure in the absence of medications. A large proportion of patients with mild to moderate hypertension and elevated sympathetic outflow and enhanced renin-aldosterone activity respond to acupuncture with blood pressure decreases of 5 mm Hg or more [9-11]. Acupuncture only needs to be applied once weekly; a course of therapy for eight weeks effectively lowers systolic and diastolic blood pressure for prolonged periods of time .
• Stimulation of a standardized set of acupoints (P5-6 and ST36-37) lowers blood pressure most effectively.
• Patients with high sympathetic outflow and renin-activity are most responsive.
This study demonstrated that systolic and diastolic blood pressures of patients with prehypertension (systolic pressures 130-140 mm Hg) and mild hypertension (140-170/85-110 mm Hg) respond to electrical stimulation of the P5-6 and ST36-37 acupoints, located over the median and deep peroneal nerves. In contrast, there is no blood pressure reduction in response to stimulation of other points LI6-7 and G37-39, located over the superficial radial and peroneal nerves. Thus, over a 4-6 week period electro acupuncture applied in standardized point specific protocol once weekly for 30 min lowers the blood pressure of hypertensive subjects not on antihypertensive medical therapy. This response is persistent in a group of high responders, which comprise approximately 70% of the patient population, lasting for a month after termination of acupuncture and for at least six months during monthly maintenance therapy [13, 14]. The mechanisms underlying these blood pressure actions of electro acupuncture include reductions in both sympathetic outflow, as reflected by plasma norepinephrine, and renin-aldosterone [15, 16].
• Electro acupuncture, through a neurohumoral mechanism, lowers blood pressure in 70% of subjects with mild hypertension when it is applied in a standardized manner at acupuncture points overlying deep somatic nerve pathways.
Tjen-A-Looi SC, Li P, Longhurst JC (2003) Prolonged inhibition of rostral ventral lateral medullary premotor sympathetic neuron by electro acupuncture in cats. Auton Neurosci 106: 119-131.
Moazzami A, Tjen-A-Looi SC, Guo ZL, Longhurst JC (2010) Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral medulla modulates cardiovascular reflex responses during acupuncture. J Appl Physiol 108: 1336-1346.
Tjen-A-Looi SC, Li P, Longhurst JC (2007) Role of medullary GABA, opioids and nociceptin in prolonged inhibition of cardiovascular sympathoexcitatory reflexes during electro acupuncture in cats. Am J Physiol Heart Circ Physiol 293: H3627-H3635.
Tjen-A-Looi SC, Li P, Longhurst JC (2006) Midbrain vIPAG inhibits rVLM cardiovascular sympathoexcitatory responses during acupuncture. Am J Physiol Heart Circ Physiol 290: H2543-H2553.
Tjen-A-Looi SC, Li P, Longhurst JC (2009) Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA. J Appl Physiol 106: 1793-1799.
Li P, Tjen-A-Looi SC, Guo ZL, Longhurst JC (2010) An arcuateventrolateral periaqueductal gray reciprocal circuit participates in electro acupuncture cardiovascular inhibition. Auton Neurosci 158: 13-23.
Tjen-A-Looi SC, Li P, Longhurst JC (2004) Medullary substrate and differential cardiovascular responses during stimulation of specific acupoints. Am J Physiol Regul Integr Comp Physiol 287: R852-R862.
Zhou W, Fu LW, Tjen-A-Looi SC, Li P, Longhurst JC (2005) Afferent mechanisms underlying stimulation modality-related modulation of acupuncture-related cardiovascular responses. J Appl Physiol 98: 872-880.
Hajjar I, Kotchen JM, Kotchen TA (2006) Hypertension: Trends in prevalence, incidence and control. Annu Rev Public Health 27: 465-490.
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Brook RD, Appel LJ, Rubenfire M, Ogedegbe G, Bisognano JD, et al. Beyond medications and diet: alternative approaches to lowering blood pressure: A scientific statement from the American Heart Association. Hypertension 61: 1360-1383.
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Mayer DJ (2000) Acupuncture: an evidence-based review of the clinical literature. Annu Rev Med 51: 49-63.
Li P, Tjen-A-Looi SC, Longhurst JC (2006) Excitatory projections from arcuate nucleus to ventrolateral periaqueductal gray in electro acupuncture inhibition of cardiovascular reflexes. Am J Physiol Heart Circ Physiol 209: H2535-H2542.
Li P, Tjen-A-Looi SC, Guo ZL, Fu LW, Longhurst JC (2009) Longloop pathways in cardiovascular electroacupuncture responses. J Appl Physiol 106: 620-630.
Li P, Tjen-A-Looi SC, Longhurst JC (2010) Nucleus raphe´ pallidus participates in midbrain-medullary cardiovascular sympathoinhibition during electro acupuncture. Am J Physiol Regul Integr Comp Physiol 299: R1369-R1376.
NCCAOM® and the NCCAOM® Academy of Diplomates Dry Needling Position What is Dry Needling? “Dry needling” is acupuncture. Acupuncture is the insertion of thin solid needles into anatomical locations to treat disease, injury, pain, or dysfunction, and to promote health and wellness. “Dry needling” is a recently coined name for an acupuncture technique that involves the insertion of acupuncture needles directly into muscles and “trigger points” for the relief of musculoskeletal pain. Licensed acupuncturists have practiced and documented this acupuncture technique, now referred to as “dry needling”, for decades in the US. Some physical therapists and other healthcare providers have claimed that “dry needling” is “new” and “not acupuncture”, because the point locations and needling style are based on anatomical structures and physiological function rather than on traditional Chinese medicine acupuncture theory. In fact, licensed acupuncturists receive training in the application of both traditional foundations of acupuncture and modern biomedical theories, and have done so since long before the term “dry needling” was invented. “Dry needling” is an advanced and invasive procedure. In the hands of a practitioner who has received limited and/or substandard training, it has the potential to cause great harm. It can be considered safe only when performed by properly trained and experienced acupuncturists. NCCAOM National Board Certified Acupuncturists™ receive hundreds of hours in the core skills required to correctly perform invasive and potentially dangerous needling techniques, assuring their competencies to insert and manipulate acupuncture needles safely. Is there a required accredited academic program for the training of physical therapists to practice dry needling acupuncture? There is no national standard entry-level academic curriculum that offers training or education in any form of needling for physical therapists. The only training in dry needling acupuncture for physical therapists are abbreviated continuing education workshops. There are no minimum hours or curriculum standards for these workshops. Is there a valid and reliable examination to test competency of physical therapists in the practice of dry needling acupuncture? No. There are no national psychometrically validated examinations to test competency of physical therapists in the practice of dry needling acupuncture. What academic and clinical practice training are required for licensed acupuncturists to practice dry needling acupuncture?
Licensed acupuncturists receive years of academic education and training in many acupuncture techniques, including what is now termed “dry needling”. Nearly all states require licensed acupuncturists to meet NCCAOM standards of eligibility and pass national board certification exams. What are the specific requirements for NCCAOM Nationally Board-Certified Acupuncturists™? To become an NCCAOM Nationally Board-Certified Acupuncturist™, applicants must, at a minimum: • Complete a minimum of three years or 1,905 hours of postgraduate education, including a minimum of 660 hours of supervised clinical training. • Graduate with a Masters degree or Professional Doctorate degree in Acupuncture or Oriental Medicine that is accredited by the Accreditation Commission for Acupuncture and Oriental Medicine (ACAOM). ACAOM is the only accreditation agency recognized for this purpose by the United States Department of Education. • Successfully pass three psychometrically validated NCCAOM National Board Examinations: o Foundations of Oriental Medicine o Acupuncture with Point Location o Biomedicine • Document completion of an NCCAOM approved course and assessment in Clean Needle Technique. • Sign and be held accountable to the NCCAOM® Code of Ethics and Grounds for Professional Discipline. Failure to comply is subject to disciplinary action. NCCAOM National Board Certification and/or a passing score on the NCCAOM certification examinations are required for acupuncturist licensure in 46 states plus the District of Columbia. What is the NCCAOM? The National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) is the only nationally accredited certification organization that assures entry-level competency of acupuncturists. The NCCAOM’s credentialing program in Acupuncture is accredited by a third-party accrediting body, National Commission for Certification Agencies (NCCA).
The NCCAOM’s mission is to assure the safety and well-being of the public and to advance the professional practice of acupuncture and Oriental medicine by establishing and promoting national evidence-based standards of competence and credentialing. NCCAOM’s top priority is to protect the public from the unsafe practice of acupuncture and Oriental medicine by individuals who do not have appropriate training and meet competency standards.
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Acupuncture for chronic pain: an update and critical overview.
Yin C, et al. Curr Opin Anaesthesiol. 2017.
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PURPOSE OF REVIEW: Acupuncture is now recommended for several chronic pain conditions. Despite supportive evidence of its effectiveness, this ancient approach is often misunderstood, and may still be underused in mainstream practice. A critical review on its effectiveness and practice integration, and mechanisms of action is essential to the medical community that is continuing to seek nonopioid therapies for chronic pain.
RECENT FINDINGS: Mounting evidence supports the effectiveness of acupuncture to treat chronic low back, neck, shoulder, and knee pain, as well as headaches. Additional data are emerging that support the use of acupuncture as an adjunct or alternative to opioids, and in perioperative settings. Findings related to its mechanisms of action include transient receptor potential cation channel vanilloid 1 activation in the periphery, microglial suppression in the cerebral cortex and spinal cord, and regulation of cytokines and other key inflammatory factors in the spinal cord. Incremental integration of acupuncture into pain medicine practices and training programmes continues to grow.
SUMMARY: Acupuncture is effective, safe, and cost-effective for treating several chronic pain conditions when performed by well-trained healthcare professionals. Further studies on its use as an adjunct or alternative to opioids, and in perioperative settings are needed.
PMID 28719458 [PubMed - as supplied by publisher]
Acupuncture shown to have benefits for treatment of some chronic pain
Published on 20 June 2017
Acupuncture is not a placebo for treatment of chronic pain. This NIHR-funded systematic review shows that acupuncture is better than usual care and sham acupuncture for pain from musculoskeletal conditions, knee osteoarthritis and chronic headache.
This NIHR review was large with over 140 trials overall, and the direct comparison with sham acupuncture helps to address uncertainty around whether acupuncture gives clinical benefit above a “placebo effect.” Acupuncture had a smaller effect on pain when compared with sham acupuncture than when compared with no acupuncture, but both comparisons showed statistically significant differences. Acupuncture also improved quality of life compared with standard care and was assessed to be a good use of NHS resources.
Acupuncture is currently recommended for the prevention of chronic headaches, but not for musculoskeletal pain or osteoarthritis pain. The findings may inform forthcoming guideline updates.
The availability of accredited acupuncturists varies across the UK. Though some are currently funded in NHS clinics, additional NHS funding for providers managing chronic pain conditions may be indicated.
Acupuncture for analgesia in the emergency department: a multicentre, randomised, equivalence and non-inferiority trial
Objectives: This study aimed to assess analgesia provided by acupuncture, alone or in combination with pharmacotherapy, to patients presenting to emergency departments with acute low back pain, migraine or ankle sprain.
Design: A pragmatic, multicentre, randomised, assessor-blinded, equivalence and non-inferiority trial of analgesia, comparing acupuncture alone, acupuncture plus pharmacotherapy, and pharmacotherapy alone for alleviating pain in the emergency department.
Setting, participants: Patients presenting to emergency departments in one of four tertiary hospitals in Melbourne with acute low back pain, migraine, or ankle sprain, and with a pain score on a 10-point verbal numerical rating scale (VNRS) of at least 4.
Main outcome measures: The primary outcome measure was pain at one hour (T1). Clinically relevant pain relief was defined as achieving a VNRS score below 4, and statistically relevant pain relief as a reduction in VNRS score of greater than 2 units.
Results: 1964 patients were assessed between January 2010 and December 2011; 528 patients with acute low back pain (270 patients), migraine (92) or ankle sprain (166) were randomised to acupuncture alone (177 patients), acupuncture plus pharmacotherapy (178) or pharmacotherapy alone (173). Equivalence and non-inferiority of treatment groups was found overall and for the low back pain and ankle sprain groups in both intention-to-treat and per protocol (PP) analyses, except in the PP equivalence testing of the ankle sprain group. 15.6% of patients had clinically relevant pain relief and 36.9% had statistically relevant pain relief at T1; there were no between-group differences.
Conclusion: The effectiveness of acupuncture in providing acute analgesia for patients with back pain and ankle sprain was comparable with that of pharmacotherapy. Acupuncture is a safe and acceptable form of analgesia, but none of the examined therapies provided optimal acute analgesia. More effective options are needed.
Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12609000989246.
“Quackery. Voodoo. Soft Science. These are just a few of the words I've heard people use to describe acupuncture.
During my training to become a physician, I was taught (maybe brainwashed) that the only real medicine is one that passes the test of double-blind trials and abides by the "standard of care."
But years of working with patients have showed me that these standards can sometimes fail to provide answers for certain ongoing health issues. I've seen acupuncture and other holistic healing modalities provide solutions.
It seems odd that inserting tiny needles into various points in the skin can be healing, but the principles behind acupuncture date back to ancient Chinese medicinal practice. You see, the body consists of 12 different energy channels, and each one has a unique point of increased electrical resistance. Acupuncture needles can help facilitate the movement of this energy.
Practitioners have used it to cure common medical conditions for thousands of years. They've developed acupuncture protocols that have been handed down through generations—slowly tweaked an perfected as they traveled across the globe.
No quackery here—just pure and simple healing.
Certain research has found that acupuncture actually lowers cortisol levels—the stress hormone that's ultimately responsible for the majority of illnesses today—in the body. As cortisol lowers, inflammation slowly reverses, unwinding the damage from a lifestyle of stress, irregular eating and poor sleep.
I recommend acupuncture to patients who are suffering migraines, hormone imbalances, and gastrointestinal issues, amount other painful conditions. I feel comfortable recommending the practice, because I've watched it work miracles in my own life.
Acupuncture, along with dietary changes and supplements, balanced my hormones and brought me to a better place of health. I experienced the tremendous healing powers of acupuncture and am confident in its role in solving the medical conditions of today. I love that acupuncture comes with minimal side effects and doesn't require additional medications.
After taking the time to understand acupuncture's complex history and implement the technique in my own health journey, I've found that the practice bridges the gap that stands between what modern science teaches us as physicians and what patients really experience.
Acupuncture and Chinese medicine are inherent parts of my medical practice, and I think they should become more ingrained in the medical model moving forward.
No quackery here—just pure and simple healing.”
-Dr. Taz Bhatia, MD, board-certified physician and professor at Emory University
Qian-Qian Li, Guang-Xia Shi, Qian Xu, Jing Wang, Cun-Zhi Liu,* and Lin-Peng Wang
Acupuncture is a therapeutic technique and part of traditional Chinese medicine (TCM). Acupuncture has clinical efficacy on various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS) and subfertility. An increasing number of studies have demonstrated that acupuncture can control autonomic nerve system (ANS) functions including blood pressure, pupil size, skin conductance, skin temperature, muscle sympathetic nerve activities, heart rate and/or pulse rate, and heart rate variability. Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities, but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. This review focused on the central mechanism of acupuncture in modulating various autonomic responses, which might provide neurobiological foundations for acupuncture effects.
Acupuncture has been practiced for over 3000 years with beneficial clinical effects on many disorders . There is sufficient evidence of the value of acupuncture to expand its application into conventional medicine and to encourage further studies of its physiological and clinical values . According to traditional Chinese medicine (TCM), “acupuncture is believed to restore the balance between Yin and Yang.” This can be translated into the Western medicine terminology as “acupuncture modulates the imbalance between the parasympathetic and sympathetic activity .” Acupuncture has been effectively used in various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS), and subfertility [4–8]. It could influence some known indicators of autonomic activities, such as blood pressure [9–11], pupil size , skin conductance , skin temperature , muscle sympathetic nerve activities , heart rate and/or pulse rate , and heart rate variability [17, 18]. Acupuncture has been proposed to treat autonomic nerve-related diseases through modulating the imbalance between the sympathetic and parasympathetic activities . Previous study has shown that changes in parasympathetic nervous activity are correlated with the amount of De-Qi (i.e., arrival of Qi) sensations during acupuncture manipulation . On the other hand, the affecting degree of acupuncture on the autonomic nerve is still unknown because part of the acupuncture effects is dependent on the De-Qi sensation .
A literature review was conducted using PubMed, EBSCOhost, and the China National Knowledge Infrastructure (CNKI). Keywords used in the searching were “acupuncture,” “brain” or “cerebrum” and “sympathetic,” “vagus,” “autonomic,” or “parasympathetic.” Articles were collected from December 2007 to present in each database. The identified 44 publications in this search were related to acupuncture basic study and central autonomic regulation. Among these 44 articles which met the criteria, 35 articles are in English and 9 articles are in Chinese. In this review, the underlying central mechanism of acupuncture-induced autonomic modulation is discussed based on basic studies that have been published in the past 5 years. We will, in particular, focus on two aspects as follows: (1) the brain region which plays an important role in initiating autonomic responses during acupuncture; (2) neurohumoral autonomic modulation of acupuncture in the central autonomic nerve system (ANS).
2. Acupuncture Effect and Central Autonomic Structures
Several studies have demonstrated that the autonomic dimension of the acupuncture stimulation was mediated by a mesencephalic and brainstem network [22, 23] (Figure 1), which is comprised of the hypothalamus, medulla oblongata, ventrolateral periaqueductal gray, and the dorsomedial prefrontal cortex. All of these areas are involved in the autonomic regulation [24–26].
Acupuncture autonomic regulation mechanism. Blue indicates the area involved in acupuncture parasympathetic regulation. Orange indicates the area involved in acupuncture sympathetic regulation.
Hypothalamus is the most important brain center that controls the ANS . As the site of autonomic regulation, hypothalamus has been proved to be involved in the pathway of electroacupuncture (EA) attenuating sympathetic activity. Impulses generated in sensory fibres in the skin connect with interneurons to modulate activities of the motoneurons hypothalamus to change autonomic functions . Increased sympathetic activity in hypertension may act as a stimulus for nitric oxide (NO) release in the hypothalamus. EA application on ST36 could effectively modulate the activity and expression of neuronal nitric oxide synthase (nNOS) in the hypothalamus of spontaneously hypertensive rats (SHR). The effect may through its connections to sympathetic and parasympathetic nervous system and also through its control of endocrine organs . However, which part of the hypothalamus that participates in the mechanism of action is still remained unclear. Effects on decreased neuropeptide Y (NPY) production due to stimulation on the paraventricular nucleus (PVN) of hypothalamus  is one of the several hypotheses which have been proposed in the literature regarding the action mechanism. The PVN of hypothalamus is a cell group that plays an important role in the regulation of sympathetic vasomotor tone and autonomic stress responses [31, 32]. Acupuncture could decrease NPY  and corticotropin-releasing hormone  expressions in the PVN and produce some specific effects on suppressing the sympathetic outflow in response to chronic stressors .
Arcuate (ARC) nucleus projects to other brain regions that regulate the sympathetic outflow include the dorsomedial hypothalamus, midbrain periaqueductal grey, rostral ventrolateral medulla (rVLM), and the nucleus of the solitary tract . Neurons in the ARC nucleus projecting to the rVLM potentially participate in EA inhibition of reflex cardiovascularsympathoexcitation . Ventrolateral periaqueductal gray (vlPAG) projections from the ARC are required for EA regulation of sympathoexcitatory presympathetic rVLM activity and the cardiovascular excitatory reflex responses, while a direct pathway between the ARC and rVLM might serve as a source of endorphins for EA cardiovascular modulation.
2.2. Medulla Oblongata
Specific regions of the medulla oblongata mediate central control of autonomic function. In the central nervous system (CNS), the rVLM is an important part of the sympathetic efferent limb of cardiovascular reflex activity and, as such, it is important in the maintenance of arterial blood pressure . It projects to the intermediolateral columns of the thoracic spinal cord, which is the origin of sympathetic preganglionic neurons . Inhibition of neuronal function in this nucleus results in large decreasing of blood pressure . EA could inhibit cardiovascular autonomic responses through modulating rVLM neurons [41, 42]. Moreover, opioids and gamma-aminobutyric acid (GABA) participate in the long-term EA-related inhibition of sympathoexcitatory cardiovascular responses in the rVLM . Activation of the nucleus raphe pallidus (NRP) attenuates sympathoexcitatory cardiovascular reflexes through a mechanism involving serotonergic neurons and 5-HT1A receptors in the rVLM during EA. Serotonergic projections from the NRP to the rVLM contribute to the EA-cardiovascular responses .
The nucleus ambiguus (NAmb), located in the ventrolateral division of the hindbrain, is considered to be an important site of origin of preganglionic parasympathetic vagal motor neurons that ultimately regulate autonomic function through the releasing of acetylcholine . The recent study of that neurons colabeled with c-Fos and choline acetyltransferase (ChAT) were activated in the EA-treated animals instead of sham EA group indicates that some NAmb neurons activated by EA are preganglionic vagal neurons . It is suggested that stimulation on a special acupoint is crucial to achieve modulate effect on autonomic function by activating NAmb neurons. It is consistent with TCM theory that genuine acupoints treatment is more effective than nonacupoints treatment based on specific physiological effects related to meridians and collections of meridian Qi.
Ventrolateral periaqueductal gray (vlPAG) is an essential midbrain nuclei that process information from somatic afferents during EA . Caudal vlPAG is a significant region in the long-loop arcuate-rVLM pathway for the EA-cardiovascular response, while the rostral vlPAG plays a major role in the reciprocal arcuate-vlPAG pathway that helps to prolong EA-cardiovascular modulation . Excitation of vlPAG neurons enhances the arcuate response to splanchnic stimulation, while blockade of vlPAG neurons limits excitation of arcuate neurons by EA. These observations indicate that EA-induced excitation of arcuate neurons requires input from the vlPAG, and the reciprocal reinforcement between the midbrain and the ventral hypothalamus serves to prolong the influence of EA on the baseline blood pressure .
2.4. Dorsomedial Prefrontal Cortex (DMPFC)
The prefrontal cortex (PFC) is vital for mediating behavioral and somatic responses to stress in the autonomic centers via projections . A near-infrared spectroscopy (NIRS) study found that the right PFC activity predominantly modulated sympathetic effects during a mental stress task . Acupuncture stimulation might decrease sympathetic activity and increase parasympathetic activity through its inhibitory effects on dorsomedial PFC activity . This might be beneficial to treat chronic pain induced by hyperactivity of the sympathetic nervous system. However, Sakatani et al. found no significant correlation between the PFC activity and ANS function during acupuncture. One of the possible explanations of the poor correlations might be that the PFC activity induced by acupuncture is not closely linked with ANS function .
3. Acupuncture Effect and Neurohumoral Modulation
Some neurotransmitters, including serotonin, opioid peptides, catecholamines, and amino acids in the brain appear to be participated in the modulation mechanism of acupuncture for certain ANS [53, 54].
3.1. Endogenous Opioids
EA was able to restore the impaired gastric motility and dysrhythmic slow waves by enhancing vagal activity, which was mediated via the opioid pathway [55, 56]. Ameliorating effects of EA at ST-36 on gastric motility might activate the central opioids that, in turn, inhibit sympathetic outflow . Although acupuncture produced significant heart rate decreases in pentobarbital-anesthetized rats, this response is related to the activation of GABAergic neurons instead of opioid . This opinion is proved by another study, which indicates that an opioid receptor-mediated transmission is not responsible for the present bradycardiac response induced by acupuncture-like stimulation . These views suggest that acupuncture treatment on different diseases may be mediated by different neurotransmitters, which is in accordance with holistic view of acupuncture treatment in TCM theory.
EA activates enkephalinergic neurons in several brain areas that regulate sympathetic outflow, including the arcuate nucleus, rostral ventrolateral medulla, raphé nuclei, among others [60, 61]. Consistent with this, Li et al.  found that EA at P5-P6 transiently stimulates the production of enkephalin in a region of the brain, which regulates sympathetic outflow. It is suggested that a single brief acupuncture treatment can increase the expression of this modulatory neuropeptide. The β-endorphin is a key mediator of changes in autonomic functions . Acupuncture may hypothetically affect the hypothalamic-pituitary-adrenal (HPA) axis by decreasing cortisol concentrations and the hypothalamic-pituitary-gonadal (HPG) axis by modulating central β-endorphin production and secretion . Some reports have also shown that a negative perception of acupuncture might produce enhanced sympathetic activation to the acupuncture stimulus , which may be mediated through endorphin pathway . It is conceivable that a specific neuroendocrine-immune network is crucial to the produce of acupuncture therapeutic effect. Further studies are required to reveal involved molecules and underlying mechanisms.
3.2. Amino Acids
Amino acid sensors could regulate the activity of vagal afferent fibers . Amino acids are directly involved in signaling the vagus pathway in the ARC . Recent studies have shown that vesicular glutamate transporter 3 (VGLUT3) in the ARC neurons [69, 70] and vlPAG [60, 71] were activated by EA at the P5-P6 acupoints. Glutamate only partially but significantly contributes to the activation of ARC-vlPAG reciprocal pathways during EA stimulation of somatic afferents . In addition, reduction of GABA release disinhibits vlPAG cells, which, in turn, modulates the activity of rVLM neurons to attenuate the sympathoexcitatory reflex responses . EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA in the vlPAG , most likely through a presynaptic CB1 receptor mechanism . Studies conducted so far on amino acids suggest that glutamate and GABA are involved in the mechanism of acupuncture for autonomic alteration. This response is closely related to vlPAG.
3.3. Nerve Growth Factor (NGF)
The NGF is a neurotrophin, which regulates the function and survival of peripheral sensory, sympathetic, and forebrain cholinergic neurons. It could modulate sensory and autonomic activity as a mediator of acupuncture effects in the CNS . The therapeutic potential of EA could modulate the activity of the ANS by a long-lasting depression of the sympathetic branch, which is associated with a peripheral downregulation of NGF in organs. Mannerås et al.  found that EA could effectively improve PCOS-related metabolic disorders, alter sympathetic markers , and normalize the DHT-induced increase of mRNANGF. The data on EA/NGF interaction in PCOS models further suggested that the decrease of NGF expression in peripheral organs could benefit EA to modulate the activity of the ANS . Although NGF in organs has been proved to be associated with the acupuncture effect on ANS, there is a lack of sufficient evidence to demonstrate the relationship between acupuncture effect and NGF in central autonomic nerve system.
Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities, but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. However, it is not clear whether different pathway is activated by specific acupoint, such as local points and distant points, or the autonomic regulation effect of acupoints from different meridians. Further rigorous RCTs are required for the study of this topic. It enables us to understand the importance of acupuncture therapy in the autonomic regulation. Then, acupuncture can be used in the treatment of various autonomic disorders as a novel alternative therapy.
The study was funded by the New Century Excellent Talents in University (NCET-09-0007) and the Technology New Star Program of Beijing (2009B46).
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Tablets made from dried leaves of the Artemisia annua plant cured 18 critically ill patients in a Congo clinic. The results suggest a new and inexpensive treatment option for the mosquito-borne disease that affects 212 million people worldwide.
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