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.

Autonomic Nervous System and Acupuncture: Brain Mapping, Napadow

Vitaly Napadow has another paper looking at the ANS (Autonomic Nervous System) and acupuncture in conjunction with brain imaging. I've highlighted some of Napadow's work here and here, he shares my interest in the ANS and acupuncture. (If you put his name in the search field of this blog you'll find some of his other work.) In this study, they look at different acupuncture points and correlate them with changes in Heart Rate (HR) and Skin Conductance (SC). They then look at the areas of the brain that are activated.

Hum Brain Mapp. 2012 Apr 14. doi: 10.1002/hbm.22091. [Epub ahead of print]Brain correlates of phasic
autonomic response to acupuncture stimulation: An event-related fMRI
study.Napadow V, Lee J, Kim J, Cina S, Maeda Y, Barbieri R,
Harris RE, Kettner N, Park K.SourceMartinos Center for Biomedical Imaging,
Department of Radiology, Massachusetts General Hospital, Charlestown,
Massachusetts; Department of Radiology, Logan College of Chiropractic,
Chesterfield, Missouri. vitaly@nmr.mgh.harvard.edu.Abstract

Autonomic nervous system (ANS) response to acupuncture has been
investigated by multiple studies; however, the brain circuitry underlying this
response is not well understood. We applied event-related fMRI (er-fMRI) in
conjunction with ANS recording (heart rate, HR; skin conductance response, SCR).
Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while
sham stimuli were delivered at control location, SH1. Acupuncture produced
activation in S2, insula, and mid-cingulate cortex, and deactivation in default
mode network (DMN) areas. On average, HR deceleration (HR-) and SCR were noted
following both real and sham acupuncture, though magnitude of response was
greater following real acupuncture and inter-subject magnitude of response
correlated with evoked sensation intensity. Acupuncture events with strong SCR
also produced greater anterior insula activation than without SCR. Moreover,
acupuncture at SP9, which produced greater SCR, also produced stronger sharp
pain sensation, and greater anterior insula activation. Conversely,
acupuncture-induced HR- was associated with greater DMN deactivation.
Between-event correlation demonstrated that this association was strongest for
ST36, which also produced more robust HR-. In fact, DMN deactivation was
significantly more pronounced across acupuncture stimuli producing HR-, versus
those events characterized by acceleration (HR+). Thus, differential brain
response underlying acupuncture stimuli may be related to differential autonomic
outflows and may result from heterogeneity in evoked sensations. Our er-fMRI
approach suggests that ANS response to acupuncture, consistent with previously
characterized orienting and startle/defense responses, arises from activity
within distinct subregions of the more general brain circuitry responding to
acupuncture stimuli. Hum Brain Mapp , 2012

Static Muscle Contraction effect on Muscle Activity, Trapezius Blood Flow, and Autonomic Indices

(Warning! Long post!)
This article (see below) is of interest to me because of the monitoring of HRV (Heart rate variability, a measure of autonomic balance, or stress response) at rest and during different challenges such as cold stress test, static hand grip test, and deep breathing test. The author was kind enough to send me an unofficial copy of his/their study.
In the introduction it is pointed out that changes in muscle activity and muscle blood flow due to stress and unfavorable muscle loads are possible factors for initiation and maintenance of muscle pain through accumulation of metabolites, which stimulate nociceptive afferents. Sometimes impaired muscle circulation can accompany chronic neck pain. In previous studies fibromyalgia patients and subjects with trapezius myalgia were found to have restricted MBF (muscle blood flow) in response to acupuncture by needle stimulation in the trapezius muscle. This may be due to aberrations in the autonomic nervous system. Indeed, various studies have found evidence for ANS (autonomic nervous system) involvement in diffuse and widespread muscle pain, and fibromyalgia patients may have elevated sympathetic tone at rest. These aberrations can be exacerbated by mental stress. Less is known about localized muscle pain, such as addressed in this article.
So in a nutshell, this study found that subjects with muscle pain showed HRV results that indicated reduced basal parasympathetic activity. Their findings (which I won't go into in detail here) indicated differences in intrinsic autonomic regulation, implying sympathetic-to-parasympathetic imbalance in chronic neck-shoulder pain. What has caused this imbalance is due to chronic pain, mental stress, or deconditioning is not known.
Their conclusion was that their findings support the hypothesis of ANS involvement at systemic and local levels in individuals with chronic neck-shoulder pain.
I bring this study to your attention for a few reasons.
1. It underscores what I tell first time patients with chronic pain from musculoskeletal problems: your pain may be worse after the first and even second acupuncture session because of an increase in blood flow that liberates many of the metabolites that can be "caught" in the vicious cycle of muscle tension and reduced blood flow.
2. It reinforces my belief in using points that have been studied and shown to decrease the stress response.
3. It reinforces my belief that autonomic balance remains a key component in pain management and in turn acupuncture treatment.
4. I was not aware of the blunted response of fibromyalgia patients to needling in the trapezius, so will have to amend and add means of increasing blood flow to the area during needling in these patients.

To read more about acupuncture, autonomic nervous system and my practice please click here.



Effects of static contraction and cold stimulation on cardiovascular autonomic indices, trapezius blood flow and muscle activity in chronic neck-shoulder pain

Department of Family Medicine and Public Health Sciences,
Division of Occupational and Environmental Health, Wayne
State University, 3800 Woodward Ave., Detroit, MI, USA
e-mail: bengt.arnetz@pubcare.uu.se
D. M. Hallman B. B. Arnetz
Department of Public Health and Caring Sciences,
Uppsala University, Uppsala, Sweden
123
Eur J Appl Physiol
DOI 10.1007/s00421-010-1813-z
Systemic cardiovascular characteristics
Subjects with muscle pain showed lower SDNN and LFHRV
during rest than the control group, indicating reduced
basal parasympathetic activity. However, there was no
increase in sympathetic activity as measured by LFnorm.
This is in line with recent studies that found diminishedHRV
in FM patients (Cohen et al. 2000) and in subjects with low
back pain (Kalezic et al. 2007). No significant difference was
found in IBI, in contrast with other studies on neck–shoulder
pain (Gockel et al. 1995; Sjo¨rs et al. 2009). In the present study, differences in autonomic reactivity
were indicated in response to HGT, but not in response to
CPT and DBT, namely the BP response to HGT was lower
in the pain group. These results are in accordance with the
blunted BP responses to exercise (Andersen et al. 2010;
Gockel et al. 1995) and normal BP responses to CPT
(Acero et al. 1999) demonstrated in previous studies
amongst subjects with neck–shoulder pain. Similar results
have been reported in patients with FM (Kadetoff and
Kosek 2010; Giske et al. 2008), indicating sympathic
hyporeactivity to various stressors (Martinez-Lavin 2007).
In the present study, however, only static contraction was
sensitive for differences in systemic BP, HRV and local
MBF, suggesting an altered exercise pressor reflex in the
pain group.
However, the increased LF reactivity observed in the
pain group during HGT should be interpreted with caution
as LF oscillations are influenced by both branches of the
ANS (Berntson et al. 1997). The current findings indicated
differences in intrinsic autonomic regulation, implying
sympathetic-to-parasympathetic imbalance in chronic
neck–shoulder pain. Whether this is a consequence of
chronic pain or due to other factors, e.g. mental stress or
deconditioning, requires further investigation. It is worth
noting, however, that although MVC was lower in the pain
Relations between symptoms and autonomic function
As expected, general health scores, as assessed with the
SF-36 questionnaire were lower in the pain group compared
to the healthy controls. More important, clinical
symptoms, e.g. dizziness and sweating, were more frequently
observed in the pain group. Using correlation
coefficients, a negative relationship was found between
disability of neck pain and resting LFnorm HRV and a
positive relation between disability and LFnorm reactivity
to static contraction. This is in line with previous findings
in low back pain (Gockel et al. 2008). Furthermore, an
inverse relationship between pain intensity and resting
SDNN was seen in the present study suggesting reduced
HRV with increased pain. Results show that it is worth to
plan treatment of neck–shoulder pain, aiming to restore
ANS balance at systemic and local levels.
myalgia had decreased vasodilatation capacity in these
muscles. Similarly, patients with generalised chronic
muscle pain, e.g. fibromyalgia (FM), had reduced MBF
following dynamic and during static exercise compared to
controls (Elvin et al. 2006). FM patients and subjects with
trapezius myalgia were found to have restricted MBF in
response to acupuncture by needle stimulation in the trapezius
muscle (Sandberg et al. 2005a).
A possible mechanism seems to be aberration in the
autonomic nervous system (ANS) (Maekawa et al. 2002;
Passatore and Roatta 2006). In chronic muscle pain, sympathetic
activity due to nociceptive stimulation may cause
disturbances of blood flow regulation in the affected
muscle and enhance muscle activation. This, in addition,
may be further exacerbated by mental stress (Larsson et al.
1995; Lundberg 2002).
Results from several studies provide evidence for ANS
involvement in diffuse and widespread muscle pain
(Martinez-Lavin 2007; Okifuji and Turk 2002). The autonomic
state in FM patients is characterised as elevated
sympathetic tone at rest, and hypo-reactivity to various
stressors, e.g. orthostatic stress, mental stress and isometric
exercise (Martinez-Lavin 2007; Giske et al. 2008). In
general, signs of ANS aberrations are reflected in heart rate
variability (HRV) and blood pressure (BP).
Although ANS may be involved in chronic muscle pain
of different origins, less is known about the degree of
autonomic involvement in localised chronic muscle pain,
especially pain in the neck–shoulder region (Leistad et al.
2008). Cardiovascular markers showed signs of sympathetic
dominance among persons with neck pain (Gockel
et al. 1995), low back pain (Gockel et al. 2008; Kalezic
et al. 2007), whiplash-associated disorders (Kalezic et al.
2010; Passatore and Roatta 2006) and distal forearm pain
among office workers (Gold et al. 2004; Sharma et al.
1997). Increased resting HR was found in subjects with
trapezius myalgia, whereas stress reactivity was unaltered
(Sjo¨rs et al. 2009).
To improve prevention and treatment, more knowledge
about ANS involvement in neck–shoulder pain is needed.
Tests are required which would differentiate between those
with and without muscle pain. Preferably, adequate assessment
should include multiple tests which target d

Good results with Acupuncture for a patient with High Blood Pressure

On a more anecdotal basis, I saw a patient today who has been coming to me for about 6 months to treat high blood pressure. He had no desire to take medications, and so was seeking some other alternatives. He is 67 and works in a stressful job as a taxi cab dispatcher. He had spent some time in Asia earlier in his working life so was open to acupuncture as an alternative.
He came twice weekly for 6 weeks and then weekly for 2 months. I treated him with classic points for decreasing rising yang, and also points that have been shown to calm the autonomic nervous system in studies, like sishencong and 6MC. We added daily herbal supplements in addition to the acupuncture treatments. In his particular case a Yin tonic was key. He now comes in once a month and has maintained his blood pressure in a healthy range. Here is a chart of his BP ( bit blurry, sorry!) It may not look super dramatic, but it's the difference between taking medications and not.

(To read more about acupuncture and my practice, please click here.)

Increased Yin-Deficient Symptoms and Aggravated Autonomic Nervous System Function in Patients with Metastatic Cancer.

This is a truly fascinating study. It is a veritable "East Meets West" extravaganza. They are looking at both symptoms of Yin Deficiency and Autonomic dysfunction as measured by Heart Rate Variability, and metastastic disease. Yin deficiency is a part of some very prominent conditions in Traditional Chinese Medicine for example, Tuberculosis, High Blood Pressure, Menopausal Hot Flashes. As an anecdotal example, one of my current patients being treated for hypertension had remarkable and sustained lowering of both systolic and diastolic blood pressure with the addition of a powerful Yin tonic. To try to correlate the symptoms of Yin Deficiency with metastasis, not only broadens the reach of TCM diagnosis, but adds to our understanding of the yin yang imbalance. What drew my attention to it was the attention paid to Autonomic Dysfunction and it is food for thought that there was a definite correlation with Yin Deficiency and autonomic imbalance. It gives us one more lens to try to make sense of vexing conditions that be difficult to treat.

(To read more about acupuncture and my practice, please click here.)
Here are some excerpts of the abstract.
1. J Altern Complement Med. 2010 Sep 28.
Increased Yin-Deficient Symptoms and Aggravated Autonomic Nervous System Function in Patients with Metastatic Cancer.Lin SC, Chen MX.
1 Department of Nursing, Show Chwan Memorial Hospital , Changhua, Taiwan .
Abstract Objectives: The objectives of this study were to investigate the
differences in severity of yin-deficiency syndrome (YDS) and function of the
autonomic nervous system (ANS) between patients with cancer with metastasis and
those without metastasis. ...
Interventions: The severity of YDS in each subject was evaluated using a questionnaire containing 12 items about symptoms and signs related to YDS. The severity of each symptom or sign was rated on a 4-point scale. Outcome measures: The total score on the questionnaire represented the severity of YDS. ANS function in each subject was evaluated by measuring heart rate variability (HRV), including time and frequency domains. ...
Results: The patients with metastasis had significantly higher average total YDS score and heart rate compared with the patients without metastasis. In contrast, they had significantly lower HRV, including standard deviation of the 5-minute average R-R
interval, total power, very-low-frequency power, and low frequency (LF) power,but not high-frequency (HF) power and LF/HF ratio. Conclusions: The results of this study indicate that patients with metastatic cancer have more severe YDS and
impaired ANS function than those without metastasis.

Acupuncture, the Autonomic Nervous system and Brain Networks

This is a technical paper exploring what occurs in the brain during acupuncture and in the ensuing time period. It also looks at the difference in the brain between sham (superficial) acupuncture and verum or real acupuncture. They also correlate this activity with Heart Rate Variability, a measure of the autonomic nervous system balance. It has the added feature of citing my research study at least twice... The abstract can be found at the link, the entire paper can be downloaded from nlm also. Some excerpts of the paper follow and short discussion.
http://www.ncbi.nlm.nih.gov/pubmed/18337009?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Pain. 2008 Jun;136(3):407-18.
Acupuncture modulates resting state connectivity in default and sensorimotor brain networks
Our results demonstrate for the first time that acupuncture can enhance the post-stimulation spatial extent of resting brain networks to include anti-nociceptive, memory, and affective brain regions. This modulation and sympathovagal response may relate to acupuncture analgesia and other potential therapeutic effects.
A review of the literature suggests that acupuncture influences a diverse set of bodily organs and functions including brain processing [25, 26] and autonomic nervous system (ANS) activity [1, 44].
It has long been known that the analgesic effects of acupuncture may actually peak long after cessation of active needle stimulation [58]. ..
Furthermore, recent reports have suggested that ANS(Autonomic Nervous System) response to acupuncture (measured by heart rate variability, HRV, [49]) may be linked to clinical response for different chronic pain populations [60]. As variable peripheral ANS response to acupuncture may influence post-stimulation brain activity, we also sought to explore the relationship between acupuncture induced ANS outflow to the heart as estimated by HRV and acupuncture induced changes in RSN (Resting state network) connectivity.
We also sought to explore the relationship between acupuncture-induced autonomic modulation and subsequent change in RSN connectivity. Increased DMN (Default Mode Network) connectivity with the hippocampal formation was anti-correlated with acupuncture-induced increase in sympathetic modulation, and correlated with parasympathetic modulation. ..
Our data contribute to these results by suggesting that when acupuncture induces a sympathovagal shift toward parasympathetic, the hippocampal formation has greater connectivity with the DefaultModeNetwork, a brain network thought to subserve self-referential cognition and autobiographical memory [14]. While pain is known to modulate autonomic outflow [18], the response is typically increased sympathetic tone. However, increased hippocampal/DMN connectivity following acupuncture was associated decreased sympathetic and increased parasympathetic modulation, suggesting that acupuncture modulation of DMN connectivity may not result from classic pain-like aspects of this complex intervention. Interestingly, other groups have found that acupuncture-induced decrease of LF/HF ratio, relating a shift in sympathovagal balance toward greater parasympathetic modulation, may relate to acupuncture therapeutic effects on chronic pain [60]. Our correlative results connecting HRV metrics with enhanced DMN connectivity should to be replicated in a clinical population to investigate this possible connection with clinical efficacy...

Not that I can speak to the entirety of this complicated and excellent study, but they are exploring why acupuncture would decrease the stress response, and why it might lead to prolonged pain relief in chronic pain patients. Since chronic pain is a syndrome where the suffering of the patient is not in direct correlation to the nociceptive stimulus, it is postulated in this paper that the acupuncture sets up a new memory of sorts which requires the default mode network connectivity with certain brain regions. They showed that the acupuncture increased the connectivity of the Default Mode Network with the hippocampus, which is connected with the Autonomic Nervous System, which caused a decrease in the stress response as demonstrated by HRV (Heart Rate Variability) analysis.
In sum, this paper may show why the stress response can be lowered by acupuncture, as my own research paper suggested.