Neuro Pathways in cardiovascular electroacupuncture response

Technical article looking at low frequency electroacupuncture in cats at P5 and P6 and the brain circuits responsible for the cardiac sympathoinhibition. Cardiac sympathoinhibition is another way to say a decrease in the stress response. The last blog post was looking at overall increased sympathetic tone in PCOS patients. This particular treatment at P5 and P6 might help to further decrease sympathetic tone in addition to the protocol described by Stener-Vitorin.
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Nucleus raphe pallidus participates in midbrain-medullary cardiovascular sympathoinhibition during electroacupuncture.
Am J Physiol Regul Integr Comp Physiol. 2010 Nov;299(5):R1369-76. Epub 2010 Aug 18.
Li P, Tjen-A-Looi SC, Longhurst JC.

Susan Samueli Center for Integrative Medicine, Department of Medicine, School of Medicine, University of California, Irvine, Irvine, California 92697-4075, USA. pengli@uci.edu
Abstract:
We have shown that electroacupuncture (EA) inhibits sympathoexcitatory rostral ventrolateral medulla (rVLM) neurons and reflex responses following activation of a long-loop pathway in the arcuate nucleus and ventrolateral periaqueductal gray (vlPAG). Additionally, EA at P 5-6 acupoints (overlying the median nerve) activates serotonin-containing neurons in the nucleus raphé pallidus (NRP), which, in turn, inhibit rVLM neurons. Although direct projections from the vlPAG to the rVLM exist, it is uncertain whether an indirect pathway through the NRP serves an important role in vlPAG-rVLM cardiovascular modulation. Therefore, the splanchnic nerve (SN) was stimulated to induce cardiovascular sympathoexcitatory reflexes, and EA was applied at P 5-6 acupoints in a-chloralose-anesthetized cats. A single-barreled recording electrode was inserted into the NRP or rVLM. Microinjection of DL-homocysteic acid (DLH) into the vlPAG increased the NRP neuronal response to SN stimulation (5 ± 1 to 12 ± 2 spikes/30 stim). Likewise, EA at P 5-6 for 30 min increased the NRP response to SN stimulation (3 ± 1 to 10 ± 2 spikes/30 stim), an effect that could be blocked by microinjection of kynurenic acid (KYN) into the caudal vlPAG. Furthermore, the reflex increase in blood pressure induced by application of bradykinin to the gallbladder and the rVLM cardiovascular presympathetic neuronal response to SN stimulation was inhibited by injection of DLH into the vlPAG, a response that was reversed by injection of KYN into the NRP. These results indicate that EA activates the vlPAG, which excites the NRP to, in turn, inhibit rVLM presympathetic neurons and reflex cardiovascular sympathoexcitatory responses.

Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth?

This article is back up information about PCOS and high sympathetic tone. They were measuring sympathetic nerve activity to the muscle vascular bed (MSNA.) They found that the heightened MSNA may account for the higher cardiovascular risk in PCOS patients, and postulate that the higher sympathetic tone may account for many of the abnormalities encountered in PCOS. They cite one previous study that explored HRV and PCOS, which I will try to track down. I'm excerpting almost in its entirety for those who might be as interested as I am in this topic.
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Yrsa Bergmann Sverrisdo´ttir,1 Tove Mogren,1 Josefin Kataoka,1 Per Olof Janson,2
and Elisabet Stener-Victorin Institute of Neuroscience and Physiology, Department of Physiology, and 2Department of Obstetrics and Gynecology,Sahlgrenska Academy, Go¨teborg University, Go¨teborg, Sweden
Am J Physiol Endocrinol Metab 294: E576–E581, 2008.

Is polycystic ovary syndrome associated with high sympathetic
nerve activity and size at birth?
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disturbance among women ofreproductive age and is proposed to be linked with size at birth and
increased prevalence of cardiovascular disease. A disturbance in the
sympathetic nervous system may contribute to the etiology of PCOS.
This study evaluates sympathetic outflow in PCOS and its relation to
size at birth. Directly recorded sympathetic nerve activity to the
muscle vascular bed (MSNA) was obtained in 20 women with PCOS
and in 18 matched controls. Ovarian ultrasonographic evaluation,
biometric, hormonal, and biochemical parameters were measured, and
birth data were collected. Women with PCOS had increased MSNA compared with
controls. MSNA was positively related to testosterone and cholesterol levels in PCOS, which, in turn, were not related to each other. Testosterone level was a stronger predictor of MSNA than cholesterol. Birth size did not differ between the study groups. This is the first study to directly address sympathetic nerve activity in women with PCOS and shows that PCOS is associated with high MSNA. Testosterone and cholesterol levels are identified as independent predictors of MSNA in PCOS, although testosterone has a stronger impact. The increased MSNA in PCOS may contribute to the increased cardiovascular risk and etiology of the condition. In this study, PCOS was not related to size at birth.

Polycystic Ovary Syndrome, Electroacupuncture and Exercise

After posting about PCOS and alternative medicine, (see here,) I was able to contact Elisabet Stener-Vitorin and she was kind enough to send a few reprints of other studies of hers. One of the more recent ones looks at low frequency electroacupuncture, exercise, and Polycystic Ovarian Syndrome. The low frequency acupuncture is the most beneficial in reducing androgen levels, acne, and increasing menstrual frequency. That's the good news. The (somewhat) bad news was that the study was carried out over 16 weeks. That's pushing it for most patients in my practice, but perhaps with such evidence on my side, the patience in my patients will improve?
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Impact of electroacupuncture and physical exercise on hyperandrogenism and
oligo/amenorrhoea in women with polycystic ovary syndrome: A randomized controlled trial
3 Elizabeth Jedel 1, Fernand Labrie 2, Anders Odén 3, Göran Holm 4, Lars Nilsson 5, Per Olof Janson 5,
4 Anna-Karin Lind 5, Claes Ohlsson 6, Elisabet Stener-Victorin 7,8 *
Am J Physiol Endocrinol Metab (October 13, 2010).
ABSTRACT
Background: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) decreases hyperandrogenism and improves oligo/amenorrhea more effectively than physical exercise or no intervention.

Results: After 16 weeks of intervention, circulating T decreased by –25%, androsterone glucuronide by –30%, and androstane-3α, 17β-diol-3glucuronide by –28% in the EA group (P=0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P=0.018 vs. exercise). After the 16-week follow-up, the acne score decreased by –32% in the EA group (P=0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-week follow-up, compared to no intervention.
Conclusion/Significance: Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Polycystic Ovary Syndrome and Acupuncture

There is a review article in the most recent issue of the American Journal of Physiological Endocrinology looking at Complementary Medical methods of approaching Polycystic Ovarian Syndrome. The authors postulate that acupuncture is useful through its "modulation of the activity in the somatic and autonomic nervous system may modulate endocrine and metabolic functions in PCOS." As readers of this blog are aware, the autonomic nervous system is of utmost interest to me, so am always heartened when other researchers and practitioners acknowledge the autonomic nervous system's role in acupuncture effectiveness. They were wary of endorsing herbal treatment for PCOS, because they were unstudied and unproven.
I was also directed to a study from 2008 concerning the evidence and physiology behind acupuncture and Polycystic Ovary Syndrome by the same author Elisabet Stener-Victorin. Stener-Vitorin has established herself as an authority on OB GYN and Acupuncture. (I shared a cab with her after the last Society for Acupuncture Research meeting a year ago and we shared our enthusiasm for the "Girl with the Dragon Tatoo" series. In Swedish the name of the first book is "Men Who Hate Women" instead of "Girl with the Dragon Tatoo." She mused that Swedes are quite realistic and dark compared to Americans. Apparently so, since would guess very few Americans would pick up a book called "Men who Hate Women.")
Excerpts from the two studies follow.
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The Physiological Basis of Complementary and Alternative Medicine for Polycystic Ovary Syndrome.
Am J Physiol Endocrinol Metab. 2011 Apr 12. [Epub ahead of print]

Raja-Khan N, Stener-Victorin E, Wu X, Legro R.

1Penn State College of Medicine.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses and infertility. Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance, obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current treatments for PCOS are only moderately effective at controlling symptoms and preventing complications. This article describes how the physiological effects of major complementary and alternative medicine (CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are mediated via activation of somatic afferent nerves innervating the skin and muscle, which via modulation of the activity in the somatic and autonomic nervous system may modulate endocrine and metabolic functions in PCOS. ..

Acupuncture in polycystic ovary syndrome: current experimental and clinical evidence.
J Neuroendocrinol. 2008 Mar;20(3):290-8.
Stener-Victorin E, Jedel E, Mannerås L.

Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. elisabet.stener-victorin@neuro.gu.se

This review describes the aetiology and pathogenesis of polycystic ovary syndrome (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms related with PCOS. PCOS is the most common female endocrine disorder and it is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity...The syndrome is associated with peripheral and central factors that influence sympathetic nerve activity. Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS. Many women with PCOS require prolonged treatment. Current pharmacological approaches are effective but have adverse effects. Therefore, nonpharmacological treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS via modulation of endogenous regulatory systems, including the sympathetic nervous system, the endocrine and the neuroendocrine system. Experimental observations in rat models of steroid-induced polycystic ovaries and clinical data from studies in women with PCOS suggest that acupuncture exert long-lasting beneficial effects on metabolic and endocrine systems and ovulation.

Medication Injuries on the Rise

From the "First, Do No Harm" department, a recent study showing that medication related injuries leading to hospitalizations has increased by 50% in recent years. The data don't take into account patients whose injury did not lead to hospitalization. My point in bringing this up, is not that all medicines are bad or unnecessary or harmful. My issue is that by considering safe alternatives, and not immediately turning to drugs for every ill could save money, and even lives.
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Some excerpts of the study follow and the emphases are mine.

April 14, 2011, 2:35 pm
Medication-Related Injuries on the Rise
By TARA PARKER-POPE

The number of people treated in hospitals in the United States for problems related to medication errors has surged more than 50 percent in recent years.

In 2008, 1.9 million people became ill or injured from medication side effects or because they took or were given the wrong type or dose of medication, compared with 1.2 million injured in 2004, according to the Agency for Healthcare Research and Quality.

Although several national reports in recent years have sounded the alarm about the toll of medication errors, the latest data show the problem continues to persist. The A.H.R.Q. data measure only patients treated in the hospital or emergency department as a result of a medication error... Some of the errors resulted from a physician prescribing the wrong drug or dose; others occurred because a pharmacist or nurse gave the wrong drug, or because a patient at home used the wrong type or dose of medication.

In 2006, the Institute of Medicine issued a report citing medication mistakes as the most common medical errors, resulting in an estimated $3.5 billion in added costs for lost wages, productivity and additional health care expenses.

The A.H.R.Q. data showed that among patients who were admitted to the hospital after taking the wrong type or dose of a drug, the most common medications to cause side effects or injuries were corticosteroids. The drugs typically are used to treat asthma, ulcerative colitis or arthritis.

Other drugs that resulted in the highest number of patients admitted to the hospital were pain relievers, blood thinners, cancer drugs and heart and blood pressure medicines.

People older than 65 were most likely to be hospitalized for side effects or medication-related injuries. However, young people were also at risk. One in five emergency cases related to medication problems were children or teenagers.