Napadow Paper Linking ANS and fMRI and acupuncture stimuli

Posted on 04/25/2012

I’ve been making my way through the Napadow paper mentioned here and here.  It is a remarkable piece of research because it not only links individual acupuncture points to their fMRI profile, but also to their ANS response and to the subjective pain response evoked. (More blog posts and practice info here.) Here is the final paragraph.

In conclusion, our approach allowed us to link ANS and
fMRI response in order to infer potential control brain circuitry underlying different autonomic responses to acupuncture stimuli at different acupoints. Our results
suggest that different sub-regions of the brain circuitry
responding to acupuncture appear to be associated with
different ANS outflow responses to needle stimuli and
may result from different sensations elicited by stimuli at
different bodily locations. This study applied er-fMRI to
link brain and ANS response to acupuncture, and future
studies should explore how this central autonomic network
response to acupuncture influences clinical
outcomes.

Acupuncture, HRV and Insomnia

Another HRV study by Litscher and his team in China. A previous post, "Part I" described HRV analysis in rats for seizures. This article explores acupuncture in patients with insomnia. Unfortunately they don't report on how the patients' insomnia symptoms responded(?) There is a link to the full paper here. At the end of the journal article in the discussion they say

The significance of our data indicates that maybe differences exist between those patients who respond to acupuncture insomnia therapy and those that do not. Further research into the use of electrocardiogram and other physiological parameters to stratify response to acupuncture therapeutic interventions is warranted.

This is exactly the point of my own research; to try to better guide treatment by adding HRV outcomes to symptomatic outcomes. Litscher merely mentions this as a possibility, but does not reveal how his data might show this.
He also says in the article that he chose to do single point acupuncture (Heart 7),unusual in clinical practice, so that he would have a point of comparison for future studies with single point auricular acupuncture.
One final point is that he found no change in LFR/HFR ratio during acupuncture, which is counter to my own findings and those of Backer, but consistent with those of Huang. As always, "more study needed."
More on my practice here.

Sino-European transcontinental basic and clinical high-tech acupuncture studies-part 2: acute stimulation effects on heart rate and its variability in patients with insomnia.
Litscher G, Cheng G, Cheng W, Wang L, Niu Q, Feng X, Gaischek I, Kuang H. Evid Based Complement Alternat Med. 2012;2012:916085. Epub 2012 Mar 4.

Research Unit of Biomedical Engineering in Anesthesia and Intensive Care Medicine and Stronach Research Unit for Complementary and Integrative Laser Medicine, TCM Research Center Graz, Medical University of Graz, 8036 Graz, Austria.

This second part of a series of Sino-European high-tech acupuncture studies describes the first clinical transcontinental teleacupuncture measurements in patients with insomnia. Heart rate (HR) and heart rate variability (HRV) measurements in 28 patients (mean age ± SD: 41.9 ± 14.6 years) were performed under standardized conditions in Harbin, China, and the data analysis was performed in Graz, Austria. Similar to the first part of the series, the electrocardiograms (ECGs) were recorded by an HRV Medilog AR12 system during acupuncture of the Shenmen point (HT7) on the left hand. HR decreased significantly (P < 0.001) during and after acupuncture stimulation of the HT7 acupuncture point. Total HRV increased significantly (P < 0.05) immediately after acupuncture stimulation, but there was no long-lasting effect. The values of the low-frequency (LF) and high-frequency (HF) band increased significantly after the stimulation compared to baseline values; however, the LF/HF ratio showed no significant changes. Together with the results of previous studies, the present results can serve as a solid basis for further development of acupressure or acupuncture stimulation equipment for complementary use in treating insomnia.

Auricular Acupuncture for Epilepsy, a Case for Vagal Stim

(No posting due to travel the last two weeks, thought I could do some but I didn't see too much in the news and my schedule chaotic.)
I did a series of posts about Litscher's work here, here and here. The abstract doesn't mention if he's looking at HRV, but I would suspect he is from his previous work. I will try to get a copy of his paper. (Sometimes it isn't possible because the abstract is out before the paper is ready.) More on my acupuncture practice here.

Evid Based Complement Alternat Med. 2012;2012:615476. Epub 2012 Feb 1.

Auricular Acupuncture May Suppress Epileptic Seizures via Activating the Parasympathetic Nervous System: A Hypothesis Based on Innovative Methods.
He W, Rong PJ, Li L, Ben H, Zhu B, Litscher G.
Source

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Abstract

Auricular acupuncture is a diagnostic and treatment system based on normalizing the body's dysfunction. An increasing number of studies have demonstrated that auricular acupuncture has a significant effect on inducing parasympathetic tone. Epilepsy is a neurological disorder consisting of recurrent seizures resulting from excessive, uncontrolled electrical activity in the brain. Autonomic imbalance demonstrating an increased sympathetic activity and a reduced parasympathetic activation is involved in the development and progress of epileptic seizures. Activation of the parasympathetic nervous system such as vagus nerve stimulation has been used for the treatment of intractable epilepsy. Here, we propose that auricular acupuncture may suppress epileptic seizures via activating the parasympathetic nervous system.

Electroacupuncture, Immunity and Autonomic Nervous System in Rats

We've seen a number of studies on acupuncture and the immune system and its effect on cellular immunity(Nerve growth factor and electroacupuncture), moxabustion and cytokine production, basophils and acupuncture for eczema, and some theoretical studies on stress and immunity but I don't recall seeing a paper drawing the specific connection between the autonomic nervous system and improved immunity. In rats no less... (Information about my practice here.)

Anesthesiology. 2012 Feb;116(2):406-14.
Electroacupuncture improves survival in rats with lethal endotoxemia via the autonomic nervous system.
Song JG, Li HH, Cao YF, Lv X, Zhang P, Li YS, Zheng YJ, Li Q, Yin PH, Song SL, Wang HY, Wang XR.
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Recent advances have indicated a complex interplay between the autonomic nervous system and the innate immune system. Targeting neural networks for the treatment of sepsis is being developed as a therapeutic strategy. Because electroacupuncture at select acupoints can modulate activities of the autonomic nervous system, we tested the hypothesis that electroacupuncture at specific acupoints could modulate systemic inflammatory responses and improve survival via its impact on the autonomic nervous system in a rat model of sepsis.
METHODS:

Sprague-Dawley male rats received electroacupuncture for 45 min before and at 1, 2, or 4 h after a lethal dose of intraperitoneal lipopolysaccharide injection (6 mg/kg). Outcomes included survival and systemic cytokine responses. Also, the possible roles of neural circuitry, including the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, were evaluated.
RESULTS:
Electroacupuncture pretreatment at the Hegu acupoints significantly attenuate systemic inflammatory responses and improve survival rate from 20% to 80% in rats with lethal endotoxemia. Such a site-specific effect requires the activation of muscarinic receptors in the central nervous system, but not increasing central sympathetic tone. In the periphery synergistic, rather than independent, action of the sympathetic and parasympathetic systems is also necessary.
CONCLUSIONS:
Electroacupuncture pretreatment has a dramatic survival-enhancing effect in rats with lethal endotoxemia, which involves the activation of efferent neural circuits of the autonomic nervous system (e.g., cholinergic antiinflammatory pathway). This approach could be developed as a prophylactic treatment for sepsis or perioperative conditions related to excessive inflammation.

HRV and Acupuncture Study: ISAMS Huang

This is the published article from this presentation from ISAMS. I'm confused about their conclusions, i.e. that heart rate variability increases in disease, when it's the opposite. They also found that the LFR/HFR was unchanged, and that HRV decreased with acupuncture which does not correspond with most studies. The finding that Sample Entropy increased corroborates my findings. (Info on my practice here.)

J Acupunct Meridian Stud. 2012 Feb;5(1):15-20. Epub 2011 Dec 9.
A naturalistic study of the effect of acupuncture on heart-rate variability.
Fasmer OB, Liao H, Huang Y, Berle JØ, Wu J, Oedegaard KJ, Wik G, Zhang Z.
Department of Clinical Medicine, Section for Psychiatry, Faculty of Medicine and Dentistry, University of Bergen, Norway; Haukeland University Hospital, Department of Psychiatry, Bergen, Norway.
OBJECTIVES:
To study the effect of acupuncture on heart rate variability (HRV) by using linear and non-linear methods of analysis.
METHODS:
40 patients were recruited consecutively, including patients with insomnia, stomachache, diarrhea, dizziness, cervical syndrome, lower back pain, gonarthritis, peripheral facial paralysis, post-traumatic organic brain syndrome and urinary retention... HRV was recorded before, during, and after acupuncture.
RESULTS:
Acupuncture substantially reduced variability, causing a 41% reduction in the standard deviation. Using a Fourier analysis, the variances both in the low frequency (LF) and the high frequency (HF) ranges were markedly reduced, but the LF/HF ratio (an indication of sympatho-vagal balance) was not altered. The HR was unchanged. The sample entropy, which is a measure of the complexity of time series, was significantly increased (+35%).
CONCLUSIONS:
Acupuncture produced a pattern of changes different from that seen in pathological conditions, where increased variability and reduced complexity is expected. (???)

Manual Acupuncture at St36 and PC6 shows increase in HRV

One more study showing that acupuncture at 6MC and St36 (the hypertension protocol of Longhurst et al) increases HRV, hence decreases stress response. In this case the stimulation was manual, but they compared "stimulating" versus "nonstimulating." For details on these two methods I would have to see the entire article. (For information on my practice, please click here.)

Stimulation of gastric slow waves with manual acupuncture at acupuncture points ST36 and PC6 - A randomized single blind controlled trial.
Witt CM, Meissner K, Pach D, Thiele C, Lüdtke R, Ghadiyali Z, Deter HC, Zimmermann-Viehoff F.
Neurogastroenterol Motil. 2012 Feb 6.
Background  To investigate the effects of stimulated and non-stimulated manual acupuncture at ST36 and PC6 on gastric myoelectrical activity and autonomic function. Methods  A total of 65 healthy volunteers were randomly assigned to a 1: 1: 2 ratio to receive either 15 min of verum acupuncture (VA) with stimulation followed by 15 min of VA without stimulation (nsVA), or 15 min of nsVA followed by 15 min of VA with stimulation (sVA), or 30 min of sham acupuncture (SA). Measures of autonomic function included electrogastrogram, electrocardiogram, impedance cardiography and assessment of blood pressure, breathing frequency, and electrodermal activity. Outcome parameters were compared between VA and SA, and between sVA and nsVA. The percentage of regular gastric slow waves (normogastria) was defined as the primary outcome. Key Results  The percentage of normogastria was not significantly different between VA and SA. Differences in secondary outcomes such as power spectrum of gastric slow waves and heart rate variability parameters were pronounced in the comparison of sVA and nsVA. During sVA, the percentage of normogastria was lower (P = 0.005), the percentage of bradygastria was higher (P = 0.003) and power ratio was higher (P < 0.001), systolic blood pressure was lower (P = 0.039) and RMSSD was higher (P < 0.001) as compared with nsVA.

Atopic Dermatitis and Acupuncture

Study looking at skin response with acupuncture and cetirizine. Both worked compared to placebo, but the flare was smaller with acupuncture. More info on my practice here.

Acupuncture compared with oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis - a patient- and examiner-blinded, randomized, placebo-controlled, crossover trial.
Pfab F, Kirchner MT, Huss-Marp J, Schuster T, Schalock PC, Fuqin J, Athanasiadis GI, Behrendt H, Ring J, Darsow U, Napadow V.Allergy. 2012 Feb 8

Department of Dermatology and Allergy, Technische Universität München, Munich, Germany; Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; Division of Environmental Dermatology and Allergy, Helmholtz Zentrum München/TUM, ZAUM-Center for Allergy and Environment, Munich, Germany; Department of Prevention and Sports Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
Abstract
BACKGROUND:

Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner-blinded, randomized, placebo-controlled, crossover trial.
METHODS:

Allergen-induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test.
RESULTS:

Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC (P > 0.1), although both therapies were significantly superior to their respective placebo interventions (P < 0.05). Flare size following VAp was significantly smaller (P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups (P < 0.001).
CONCLUSIONS:

Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention.

Tale of Two Articles: Migraine and the Gut

Consider the article yesterday in the SF Chronicle "UCSF doctors see colic-migraine link."
And an elaborate study out of China looking at different acupuncture treatment approaches for migraine prophylaxis. Acupuncture for migraine prophylaxis: a randomized controlled trial (full text at link.)
What is of interest between the two? The UCSF study finds that mothers with migraines are more likely to have babies with colic. Of course, we still have no idea what causes colic, even though the name implies something to do with the GI system. But there is a link between migraines and abdominal pain in youths called "abdominal migraine." Some children suffer bouts of nausea or dizziness before developing more classic headache symptoms as adults. There clearly is some link between the gut and migraine.
Then consider the study out of China. It compares classic treatment for migraine using Shao Yang points (Gall Bladder, lateral points.) And Yang Ming or treatment using stomach points. Though Shao Yang had slightly better results, both showed a decrease in migraines compared to controls (sham acupuncture.)
So wouldn't it be fascinating, in light acupuncture's effect on the gut, to compare different electroacupuncture treatments using acupuncture points for the gut for migraine prophylaxis? (Too many studies to do, too little time.)

I would also like to mention a fascinating anecdote related to me by a patient. Her horse had a common type of colic in which they get distension, bloating and obstruction. An acupuncture veterinarian put some needles near the nostils of the horse (Large Intestine Meridian) and the horse was cured. Maybe a clue for migraine treatment??

(More on my practice here.)

Autonomic Nervous System:Acupuncture and Low Back Pain

This study evaluates the autonomic nervous system (stress response) in patients with low back pain comparing electroacupuncture (10 sessions) and an antiinflammatory medication. What they found was that both groups had pain relief, but the acupuncture group more so. There was an improvement in the stress response in the acupuncture group also. (For info on my practice please click here.)

Autonomic status and pain profile in patients of chronic low back pain and following electro acupuncture therapy: a randomized control trial.
Shankar N, Thakur M, Tandon OP, Saxena AK, Arora S, Bhattacharya N.Indian J Physiol Pharmacol. 2011 Jan-Mar;55(1):25-36.
Department of Physiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi.

Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system. Chronic low back pain (LBP) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture. This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy. Chronic LBP patients (n=60) were recruited from the Department of Orthopaedics, GTB Hospital, Delhi. Age and sex matched healthy volunteers were selected as controls (n=30). Following a written consent, LBP patients were randomly allocated into two study groups - Group A received 10 sittings of electro acupuncture, on alternate days, at GB and UB points selected for back pain, while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy. Controls were assessed once while the patients were assessed twice, before and after completion of the treatment program (3 weeks). The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E: I ratio, 30:15 ratio, postural challenge test and sustained handgrip test. Pain intensity was measured with the visual analogue scale (VAS) and the global perceived effect (GPE). Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls (P<0.05 to P<0.001 in different variables). Following treatment, both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity. There was also a considerable relief of pain in both groups, however, the acupuncture group showed a better response (P<0.01). We conclude that there is autonomic dysfunction in chronic LBP patients. Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases.

Spinal Serotonin and Electroacupuncture: University of Maryland Group

University of Maryland with another elegant study exploring the precise spinal neuro-receptors involved in electroacupuncture. They employ the model that they have used repeatedly, iwhich is to inject Freund's adjuvant into the joint space of cats hind paws. This is an irritant which mimics arthritis. They then use hind paw withdrawal latency to measure the effects of acupuncture versus control.
But don't we all know that acupuncture is just placebo??
(Information on my practice here.)

Involvement of spinal serotonin receptors in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model.
Zhang Y, Li A, Xin J, Lao L, Ren K, Berman BM, Tan M, Zhang RX.
Neurochem Res. 2011 Oct;36(10):1785-92.
Center for Integrative Medicine, School of Medicine, University of Maryland, 685 W Baltimore street, MSTF Rm 8-22, Baltimore, MD 21201, USA.


We previously showed that electroacupuncture (EA) activates medulla-spinal serotonin-containing neurons. The present study investigated the effects of intrathecal 5,7-dihydroxytryptamine creatinine sulfate, a selective neurotoxin for serotonergic terminals, the 5-hydroxytryptamine 1A receptor (5-HT1AR) antagonist NAN-190 hydrobromide and the 5-HT2C receptor (5-HT2CR) antagonist SB-242,084 on EA anti-hyperalgesia. EA was given twice at acupoint GB30 after complete Freund's adjuvant (CFA) injection into hind paw. CFA-induced hyperalgesia was measured by assessing hind paw withdrawal latency (PWL) to a noxious thermal stimulus 30 min post-EA. Serotonin depletion and the 5-HT1AR antagonist blocked EA anti-hyperalgesia; the 5-HT2CR antagonist did not. Immunohistochemical staining showed that spinal 5-HT1AR was expressed and that 5-HT2CR was absent in naive and CFA-injected animals 2.5 h post-CFA. These results show a correlation between EA anti-hyperalgesia and receptor expression. Collectively, the data show that EA activates supraspinal serotonin neurons to release 5-HT, which acts on spinal 5-HT1AR to inhibit hyperalgesia.

Post Spinal Nerve Ligation Hypersensitivity Relieved by Manual Acupuncture (in rats)

This study is looking at acupuncture effectiveness for neuropathic pain. They simulate neuropathic pain by ligating a spinal nerve in the rat and then using traditional acupuncture point stimulation compared with gabapentin.

Manual acupuncture inhibits mechanical hypersensitivity induced by spinal nerve ligation in rats.
Cidral-Filho FJ, da Silva MD, Moré AO, Córdova MM, Werner MF, Santos AR.
Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil.
Abstract

Manual acupuncture (MA) has presented analgesic activity against neuropathic pain in patients and animal models, yet a series of questions remain: Is MA effectiveness dependent of acupoint selection or combination? Is it equally efficient when treatment starts on the initial (acute) or sub-chronic phase of spinal nerve ligation (SNL)-induced neuropathy? Is MA effect related to the release of endogenous opioids? Does MA produce similar effects to gabapentin? To answer these questions rats submitted to the L5/L6 SNL injury were treated with unilateral MA (ST36 (Zusanli), SP6 (Sanyingjiao) or ST36+SP6 acupoint stimulation); or with gabapentin (30 mg/kg i.p., used as positive control). Both acupoints have been demonstrated to present analgesic activity and are used in clinical practice and basic science research. In addition, we investigated the influence of naloxone (1 mg/kg i.p., a nonselective opioid receptor antagonist) on MA treatment and also the effect of unilateral ST36+SP6 MA treatment beginning acutely (5 days) or sub-chronically (14 days) after SNL. Our results demonstrate that single or combined unilateral stimulation was able to reduce mechanical hypersensitivity with treatment beginning in both acute and sub-chronic phases of SNL-induced neuropathy; MA effect was blocked by naloxone, and finally; SP6+ST36 MA presented similar effect to gabapentin (30 mg/kg). In conclusion, our results demonstrate, for the first time, that unilateral MA (ST36, SP6 or ST36+SP6) reduces hypersensitivity induced by the SNL with effect dependent of the opioid system and comparable with the one obtained with gabapentin (used as positive control).

For more information on my practice, please click here.

Acupuncture for Eczema, the role of Basophils

Nice study, but small, looking at acupuncture's effect on the "itch" of eczema and the correlation with basophils. Post on an acupuncture study on eczema here from Napadow. Info on my practice here.

J Altern Complement Med. 2011 Apr;17(4):309-14. Epub 2011 Mar 28.
Effect of acupuncture on allergen-induced basophil activation in patients with atopic eczema:a pilot trial.
Pfab F, Athanasiadis GI, Huss-Marp J, Fuqin J, Heuser B, Cifuentes L, Brockow K, Schober W, Konstantinow A, Irnich D, Behrendt H, Ring J, Ollert
Department of Dermatology and Allergy, Technische Universität München, Biedersteiner Straße 29, Munich, Germany. florian.pfab@lrz.tum.de
Abstract
OBJECTIVE AND METHODS:

The crucial symptom of atopic eczema is itch. Acupuncture has been shown to exhibit a significant effect on experimental itch; however, studies focusing on clinical itch in atopic eczema and corresponding mechanisms are lacking. The study design was a unicenter, single-blinded (observer), prospective, randomized clinical pilot trial with an additional experimental part. In 10 patients with atopic eczema, we investigated the effect of acupuncture treatment (n = 5) compared to no treatment (n = 5) on itch intensity and in vitro basophil CD63 expression upon allergen stimulation (house dust mite and timothy grass pollen) in a pilot trial.
RESULTS:
Mean itch intensity in a visual analog scale was rated significantly lower in the acupuncture group (-25% ± 26% [day 15-day 0]; -24% ± 31% [day 33-day 0]) than in the control group (15% ± 6% [day 15-day 0]; 29% ± 9% [day 33-day 0]). From day 0 (before treatment) to day 15 (after 5 acupuncture treatments) as well as day 33 (after 10 acupuncture treatments), the acupuncture group showed less CD63 positive basophils than the control group regarding stimulation with house dust mite and grass pollen allergen at various concentrations (5 ng/mL, 1 ng/mL, 0.5 ng/mL, or 0.25 ng/mL).
CONCLUSIONS:
Our results show a reduction of itch intensity and of in vitro allergen-induced basophil activation in patients with atopic eczema after acupuncture treatment. Reducing basophil activation can be a further tool in investigating the mechanisms of action of acupuncture in immunoglobulin E-mediated allergy. Due to the limited number of patients included in our pilot trial, further studies are needed to strengthen the hypothesis.

Placebo and Acupuncture vs Acupuncture for Dogs

Compare and contrast.
A study looking AGAIN at acupuncture for osteoarthritis after the biggest study ever done on acupuncture put the placebo issue to rest. Why don't we see this scrutiny with anti-depressant studies? Or stents? There can actually be some hazards with either of those...
Meanwhile other groups are moving on and using acupuncture in dogs for post operative pain. Because it's all about the placebo effect...

Practice, practitioner, or placebo? A multifactorial, mixed-methods randomized controlled trial of acupuncture.
White P, Bishop FL, Prescott P, Scott C, Little P, Lewith G
Faculty of Health Sciences, University of Southampton, Highfield, Southampton, UK.
Abstract
The individual practitioner and the patient's belief had a significant effect on outcome. The 2 placebos were equally as effective and credible as acupuncture. Needle and nonneedle placebos are equivalent. An unknown characteristic of the treating practitioner predicts outcome, as does the patient's belief (independently). Beliefs about treatment veracity shape how patients self-report outcome, complicating and confounding study interpretation.

Electroanalgesia for the postoperative control pain in dogs.
Cassu RN, Silva DA, Genari Filho T, Stevanin H.Acta Cir Bras. 2012 Jan;27(1):43-8.
Unoeste, Presidente Prudente, SP, Brazil.
To evaluate the analgesic and neuroendocrine effects of electroanalgesia in dogs undergoing ovariohysterectomy.
RESULTS: EA and EAD- treated dogs had lower pain scores than DER treated dogs one hour postoperatively. Fewer EA and EAD-treated dogs required rescue analgesia. Serum cortisol did not differ among treatments.
CONCLUSION:Preoperative application of electrical stimuli to acupuncture points isolated or in combination with peri-incisional dermatomes provides a reduced postoperative opioid requirement and promotes an effective analgesia in dogs undergoing ovariohyterectomy.

So do dogs' beliefs influence outcomes too?

Info on my practice here.

Dr. Peng Li's Presentation Summarizing 50 years of Acupuncture Research

Dr. Li covered quite a bit of ground as you can imagine during his talk at ISAMS. I'll just feature a few highlights over the next few blog posts.
This slide is taken from Goldman's work entitled "Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture."
Dr. Li then goes on to describe the different protocols for choosing acupuncture points
1. Ashi point- local acupoints for Pain treatment
local release of chemicals, e.g. adenosine (A1 receptor).
convergent input to nearby spinal segment.
2.Acupoints related to Spinal segments
convergent inputs from internal organs and somatic n.
Gate control theory
3. Distant acupoints- supra-spinal integration
Selection of Acupoints

Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture.

Insomnia in Menopausal Women Treated with Auricular Acupuncture:HRV correlation

(Warning, this post is only for those interested in the tiny niche of acupuncture and HRV.)
Gotta love this study since it correlates HRV with treatment outcomes. Yay! Though there has been quite a bit of research on HRV and acupuncture, there has been precious little looking at whether HRV response correlates with clinical outcomes. In this study they found nLF to go down and nHF to go up in patients who had effective treatment (i.e. less insomnia) and for nLF to go up in the nonresponders. Progress! Some researchers insist that one needs to look only at non-normalized values and that HF is more predictive than LF, but we'll take what we can get.

Menopause. 2011 Jun;18(6):638-45.

The relationship of subjective sleep quality and cardiac autonomic nervous system in postmenopausal women with insomnia under auricular acupressure.

Kung YY, Yang CC, Chiu JH, Kuo TB.

Source

Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.

Abstract

OBJECTIVE:

The aim of this study is to examine the relationship between the changes in self-reported sleep symptoms and cardiac sympathovagal activity among women with postmenopausal insomnia (PI) who received auricular acupressure (AA) therapy.

METHODS:

A pretest/posttest study design was conducted at Taipei Veterans General Hospital, Taiwan, from August 2008 to July 2009. Forty-five women (mean ± SD age, 56.2 ± 5.4 years) with PI (4.9 ± 3.5 years of insomnia) received an AA therapy course on five auricular points every night before going to sleep for 4 weeks. Heart rate variability (HRV), the Chinese version of the Pittsburgh Sleep Quality Index, and the Menopause Rating Scale were measured before and after AA treatment.

RESULTS:

The total sleep duration and sleep efficiency were increased, and the sleep latency was shortened significantly (P < 0.01) after AA therapy. The total Menopause Rating Scale and somatovegetative subscale scores were reduced significantly (P < 0.05) after the intervention. A greater percentage change in Pittsburgh Sleep Quality Index was moderately correlated with both a lower percentage change in high-frequency power of HRV (r = -0.660, P < 0.001) and a greater percentage change in normalized low-frequency power (nLF) of HRV (r = 0.599, P < 0.001). An elevation of high-frequency power and a reduction of nLF of HRV were observed in the responder group, whereas a raise in nLF of HRV was noted in the nonresponder group.

CONCLUSIONS:

This study suggests that AA intervention leads to more cardiac parasympathetic and less cardiac sympathetic activity, which contributes to the improvement of PI.

For more information about my practice click here.

For more information about acupuncture and HRV, please click here.

More ISAMS:Lixing Lao presenting recent studies shoulder pain, electroacupuncture and inflammation

More from the ISAMS conference.
The indomitable Dr. Lixing Lao gave a presentation on the current state of Acupuncture research. He reported on a German Study looking at shoulder pain published in Pain by Molsberger. This was a study comparing sham, with verum and conservative management. The verum acupuncture group showed 65% of patients with at least 50% improvement in their pain and well being scores persisting to the 3 month mark. Sham had 40% improvement, but that deteriorated by the 3 month mark.
"“Research should be supported to provide a better understanding of the mechanisms involved, and such research may lead to improvements in treatment.”
(That's what I'm trying to do!!)
In persistent inflammatory pain, there is a dual mechanism of electroacupuncture (10 Hz, but not 100Hz)in rats. There is a direct effect on the CNS, an analgesic mechanism, there is also an effect on the hypothalamus/pituitary/adrenal axis leading to less edema. (I discussed that study here.) They discuss the exact mechanism involving CRF. They also show that EA significantly increased plasma ACTH levels compared to sham EA leading to a decrease in edema. They also show that EA significantly increased plasma corticosterone levels compared to sham EA. (This makes me wonder if that's why I often see no decrease in the stress response with electroacupuncture.
Conclusion
EA activates CRF-containing neurons to significantly increase plasma corticosterone and ACTH levels, suggesting that EA activates the HPA.(Hypothalamus/Pituitary/Adrenal)
•Corticosterone, ACTH and CRF receptor antagonists blocked EA anti-inflammation but not anti-hyperalgesia, suggesting that corticosterone, ACTH and CRF are involved in EA anti-inflammation but not EA anti-hyperalgesia.
(For information about my practice please click here.)

Central Neural Actions of Acupuncture, Insights from Brain Imaging

This is the abstract from Richard Harris' talk at the ISAMS conference. Unfortunately, I had to leave before he gave his talk and it is a bit complicated. I have the slides from the talk and once I make my way through them, I will try to make some sort of comment. The abstract follows and after that is the final slide of the presentation.

Central Neural Actions of Acupuncture, Insights from Brain Imaging
Richard Harris PhD, Assistant Professor, Chronic Pain and Fatigue Research Center Department of Anesthesiology, University of Michigan
Functional neuroimaging has been used to study the mechanistic effects of acupuncture for the past 12 years. Over this time researchers have found specific effects of acupuncture on the central nervous system, both in healthy controls as well as in diseased populations. These effects appear to be largely divergent from the “placebo effect”. An investigation of the temporal dynamics of acupuncture yields a complex
array of actions on the central nervous system. During needle insertion and manipulation, acupuncture activates sensory cortical regions while deactivating the limbic system. The degrees of these effects are distinct from the sensation of pain and are related to the “De Qi” sensation. These effects are also more prevalent during electrical stimulation as compared to manual needle manipulation. Following needle removal, modulation of brain connectivity is observed wherein cortical and brain stem regions alter connection strengths between the pain network as well as the Default Mode Network. These effects may be related to analgesia. Over the course of long-term therapy, with multiple treatment sessions, there is a build-up of effects that involve synaptic plasticity and/or changes in synaptic strengths, involving dynamic regulation of neurotransmitter receptors. Finally, immediate actions of acupuncture on the nervous system are modulated over the course of therapy such that the effects of one acupuncture session may be different from a subsequent session. Acupuncture effects are clearly complex and multifactorial, having impact on the central nervous system as assessed by multiple neuroimaging methods.

(This is the final slide from the presentation.)
What if Mechanisms of Acupuncture and Sham are Different?
Implications for clinical trials: specific effects of needling are not additive with placebo effects. Would a pathway analysis make more sense?
Synergistic effects of acupuncture with other interventions.
Exogenous opiates administered following a course of acupuncture may be more effective. (Reduction in post surgical opiate use. Kotani et al. Anesthesiology2001.)
Acupuncture is not a sham.

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Treating Hypertension (High Blood Pressure) in the Acupuncture Clinic

This is the abstract from a study on hypertensive patients from Professor John Longhurst's lab. It is a sort of summary of his findings discussed here and here.
A few comments... He uses electroacupuncture because he says it's easier to make it standard across patients. This was something I noticed repeatedly at the conference: most researchers are using electroacupuncture. I had a few different discussions with Dr. Longhurst, and he thinks that if you don't do electroacupuncture, you're really not stimulating because the stimulus goes away during the session. I don't agree with that. I think that the needles provoke a "micro-injury" just by being there and work just fine, even if you don't repeatedly stimulate them. Manual acupuncture, without electro, is my standard operating procedure. I use electro acupuncture if I'm following a specific protocol, for example for infertility or PCOS, or in musculoskeletal cases where the patient has reached a "plateau." I hardly ever start with electrical stimulation because of the tendency for it to aggravate the condition and the patient. I would never have the heart to do electrical stimulation at P6, as they do in this study. It's such a sensitive spot, I will try their other choice of LI11 and LI10 which is equally effective according to their work.
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Acupuncture Treatment of Hypertension
John C. Longhurst, MD, PhD and Peng Li, MD, Department of Medicine, University of California, Irvine
Heart disease in both men and women has become the major cause of death and disability in both developed and developing countries. Coronary atherosclerosis, the leading cause of heart disease, has a number of risk factors that increase its incidence. These include hypertension, hypercholesterolemia, diabetes mellitus, family history, obesity, physical inactivity and chronic stress. Hypertension, in particular, is reversible if patients are treated early and blood pressure is lowered to normal levels. Although a number of drug therapies have been shown to be valuable in lowering this risk factor, many patients do not take medications faithfully because of their common side effects and need for daily dosing. As such, there is a strong rationale developing alternative regimens to control blood pressure. One such therapy is acupuncture. Acupuncture is a form of integrative medicine that has substantial evidence demonstrating its mechanisms of action to lower sympathetic outflow, one of the major causes of elevated blood pressure. For example, studies in our laboratory show that, through an opioid mechanism in the brain stem, acupuncture can lower reflex elevations in blood pressure. Furthermore, we have shown that low frequency, low intensity electroacupuncture at some acupoints, such as P5-P6 and S36-S37, is most effective in lowering elevated blood pressure for prolonged periods of time. In the last decade several studies have been conducted showing that acupuncture is capable of lowering blood pressure to a small extent for the period of time during which it is applied. Although these studies indicate a possible role for acupuncture in treating hypertension, they have been confounded by use of a variety of different acupoints, some of which may not have strong cardiovascular actions, use of manual acupuncture, which unlike electroacupuncture cannot be standardized between patients, the use of very frequent acupuncture, which because of patient incompliance could limit success for long-term treatment, and the absence of regular follow-up, which does not provide an understanding of the duration of acupuncture’s action. To overcome these obstacles, we have embarked on a program of treatment of patients with mild to moderate hypertension using 30 min of low intensity (2 mA), low frequency (2 Hz) electroacupuncture at P5-P6 and S36-S37, a modality and site of action that we have shown has the greatest action on sympathetic outflow and elevated blood pressure in our experimental studies. Furthermore, all patients were off antihypertensive medications for the duration of the study and agreed to acupuncture treatment once weekly for an eight week period with a further follow-up for an additional eight weeks to determine acupuncture’s duration of action. Ambulatory automated blood pressure monitoring demonstrated that both average and 24 hour peak systolic and mean arterial blood pressures were lowered by electroacupuncture after 4-6 weeks of therapy by as much as 11-18 mmHg and that the duration of action of lasted for up to 4 weeks after termination of acupuncture in 73% of individuals treated. Conversely, 69% of a group of control hypertensive subjects treated at LI6-LI7 and GB37-GB39 (cardiovascular inactive acupoints demonstrated in our experimental studies), , did not demonstrate any change in blood pressure. These studies, guided by our results in experimental studies, suggest that low intensity and low frequency electroacupuncture applied once weekly at 2 acupoints demonstrated to have a strong influence on sympathetic activity after 4-6 weeks demonstrate a profound and prolonged antihypertensive response in many patients with mild or moderate hypertension. Additional work is needed to determine the optimal frequencies of repetitive stimulation during the initial period of intervention as well as during follow-up therapy for reinforcement of the blood pressure lowering action of acupuncture. Supported by grants from the NIH, HL063313 and HL072125-10, the Dana and Adolph Coors Foundations.

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Acupuncture's Effect in Induced Arthritis in Mice

This was my favorite presentation at the conference. It was convincing in that it showed decreases in different measures of inflammation and immune function after acupuncture. But what was sort of mind blowing for me was that they only used an acupoint on the back, Ming Men. None of the standard points at or around the limb in question. I never had the chance to ask the author how they picked this protocol. Might have been easier to do with unrestrained rats, but fascinating, nonetheless. Perhaps I should incorporate this is the clinic? A single point for arthritis??

Mechanisms of acupuncture's action in arthritis and immune modulation
Tadashi Hisamitsu, MD, PhD
Showa University, Tokyo, Japan
To evaluate the effects and possible mechanism of acupuncture on the arthritic disease, the influence of electro-acupuncture (EA) and Mox on collagen-induced arthritis (CIA) animal was examined. DBA/1J mice were immunized with bovine type II collagen (CII). The main incidence of arthritis started about on day 30 and lasted to day 60 after the first immunization. EA stimulation or Mox, begun on day 21 simultaneously with the second immunization, was applied three times a week for 3 weeks at the acu-point equivalent to GV4 (governor vessel 4, Ming Men, Meimon). The results showed that EA and Mox delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, these stimulation significantly increased serum IL-6 concentration and regulatory T cell (CD4+ CD25+ Foxp3+ T cell) number, and decreased splenic endogenous IL-1 β and serum prostaglandin E2 (PGE2) concentration. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1β and PGE2 and activation of regulatory T cell. In the Oriental Medicine, reduction of the blood fluidity is one of the important pathological symptom. In the pain and stress model animal, the blood fluidity is markedly lowered like “a stagnant blood”. Increase of platelet adhesion and/or reduction of erythrocyte deformability results from sympathetic activation, increase of blood ATP level and increase of oxidative stress may have important role on this changes. EA applied several acu-points significantly improved these changes.

Results: Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes

Results

nIt is feasible to evaluate HRV in the acupuncture clinic both by nonlinear and linear measurements. The total calculation time is 7 minutes.

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nPatients who responded to their acupuncture treatment tended to exhibit a decrease in their LFR/HFR ratio from segment “a” to segment “b”, an increase in their SD1/SD2, and an increase in their Samp En: all of these trends indicating a decrease in their stress response

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nNon-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR from minute and a decrease in their SD1/SD2 from the first to second time window, and an increase in their Sample Entropy

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nThere were notable exceptions, i.e. patients who were strong responders, who did not exhibit the consistent pattern above. In these patients, Sample Entropy was the strongest predictor of successful treatment.

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nBecause of the prevalence of artifact in heart rate monitoring, the addition of nonlinear measures gives added confidence to the measurements obtained.

nChanging the needle placement prescription and type of stimulation changed outcomes corresponding to HRV results in some cases.
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