On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an international conference to mark the tenth anniversary of the landmark NIH [National Institutes of Health] Consensus Development Conference on Acupuncture. More than 300 acupuncture researchers, practitioners, students, funding agency personnel, and health policy analysts from 20 countries attended the SAR meeting held at the University of Maryland School of Medicine, Baltimore, MD. This paper summarizes important invited lectures in the area of basic and translational acupuncture research. Specific areas include the scientific assessment of acupuncture points and meridians, the neural mechanisms of cardiovascular regulation by acupuncture, mechanisms for electroacupuncture applied to persistent inflammation and pain, basic and translational research on acupuncture in gynecologic applications, the application of functional neuroimaging to acupuncture research with specific application to carpal-tunnel syndrome and fibromyalgia, and the association of the connective tissue system to acupuncture research. In summary, mechanistic models for acupuncture effects that have been investigated experimentally have focused on the effects of acupuncture needle stimulation on the nervous system, muscles, and connective tissue. These mechanistic models are not mutually exclusive. Iterative testing, expanding, and perhaps merging of such models will potentially lead to an incremental understanding of the effects of manual and electrical stimulation of acupuncture needles that is solidly rooted in physiology.
De qi is an important traditional acupuncture term used to describe the connection between acupuncture needles and the energy pathways of the body. The concept is discussed in the earliest Chinese medical texts, but details of de qi phenomenon, which may include the acupuncturist's and/or the patient's experiences, were only fully described in the recent hundred years. In this paper, we will trace de qi historically as an evolving concept, and review the literature assessing acupuncture needle sensations, and the relationship between acupuncture-induced de qi and therapeutic effect. Thereafter, we will introduce the MGH Acupuncture Sensation Scale (MASS), a rubric designed to measure sensations evoked by acupuncture stimulation as perceived by the patient alone, and discuss some alternative statistical methods for analyzing the results of this questionnaire. We believe widespread use of this scale, or others like it, and investigations of the correlations between de qi and therapeutic effect will lead to greater precision in acupuncture research and enhance our understanding of acupuncture treatment.
The mammalian tongue is believed to fall into a class of organs known as muscular hydrostats, organs for which muscle contraction both generates and provides the skeletal support for motion. We propose that the myoarchitecture of the tongue, consisting of intricate arrays of muscular fibers, forms the structural basis for hydrostatic deformation. Owing to the fact that maximal diffusion of the ubiquitous water molecule occurs orthogonal to the short axis of most fiber-type cells, diffusion-weighted magnetic resonance imaging (MRI) measurements can be used to derive information regarding 3-D fiber orientation in situ. Image data obtained in this manner suggest that the tongue consists of a complex juxtaposition of muscle fibers oriented in orthogonal arrays, which provide the basis for multidirectional contraction and isovolemic deformation. From a mechanical perspective, the lingual tissue may be considered as set of continuous coupled units of compression and expansion from which 3-D strain maps may be derived. Such functional data demonstrate that during physiological movements, such as protrusion, bending and swallowing, hydrostatic deformation occurs via synergistic contractions of orthogonally aligned intrinsic and extrinsic fibers. Lingual deformation can thus be represented in terms of models demonstrating that synergistic contraction of fibers at orthogonal or near-orthogonal directions to each other is a necessary condition for volume-conserving deformation. Evidence is provided in support of the supposition that hydrostatic deformation is based on the contraction of orthogonally aligned intramural fibers functioning as a mechanical continuum.
BACKGROUND: Acupuncture stimulation elicits deqi, a composite of unique sensations that is essential for clinical efficacy according to traditional Chinese medicine (TCM). There is lack of adequate experimental data to indicate what sensations comprise deqi, their prevalence and intensity, their relationship to acupoints, how they compare with conventional somatosensory or noxious response. The objective of this study is to provide scientific evidence on these issues and to characterize the nature of the deqi phenomenon in terms of the prevalence of sensations as well as the uniqueness of the sensations underlying the deqi experience.
METHODS: Manual acupuncture was performed at LI4, ST36 and LV3 on the extremities in randomized order during fMRI in 42 acupuncture naïve healthy adult volunteers. Non-invasive tactile stimulation was delivered to the acupoints by gentle tapping with a von Frey monofilament prior to acupuncture to serve as a sensory control. At the end of each procedure, the subject was asked if each of the sensations listed in a questionnaire or any other sensations occurred during stimulation, and if present to rate its intensity on a numerical scale of 1-10. Statistical analysis including paired t-test, analysis of variance, Spearman's correlation and Fisher's exact test were performed to compare responses between acupuncture and sensory stimulation.
RESULTS: The deqi response was elicited in 71% of the acupuncture procedures compared with 24% for tactile stimulation when thresholded at a minimum total score of 3 for all the sensations. The frequency and intensity of individual sensations were significantly higher in acupuncture. Among the sensations typically associated with deqi, aching, soreness and pressure were most common, followed by tingling, numbness, dull pain, heaviness, warmth, fullness and coolness. Sharp pain of brief duration that occurred in occasional subjects was regarded as inadvertent noxious stimulation. The most significant differences in the deqi sensations between acupuncture and tactile stimulation control were observed with aching, soreness, pressure and dull pain. Consistent with its prominent role in TCM, LI4 showed the most prominent response, the largest number of sensations as well as the most marked difference in the frequency and intensity of aching, soreness and dull pain between acupuncture and tactile stimulation control. Interestingly, the dull pain generally preceded or occurred in the absence of sharp pain in contrast to reports in the pain literature. An approach to summarize a sensation profile, called the deqi composite, is proposed and applied to explain differences in deqi among acupoints.
CONCLUSION: The complex pattern of sensations in the deqi response suggests involvement of a wide spectrum of myelinated and unmyelinated nerve fibers, particularly the slower conducting fibers in the tendinomuscular layers. The study provides scientific data on the characteristics of the 'deqi' response in acupuncture and its association with distinct nerve fibers. The findings are clinically relevant and consistent with modern concepts in neurophysiology. They can provide a foundation for future studies on the deqi phenomenon.
Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI-4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HC). CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short-term brain response to acupuncture stimulation, as well as the influence of longer-term acupuncture therapy effects on this short-term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non-specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala--the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter-digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala.
Acupuncture is an ancient East Asian healing modality that has been in use for more than 2000 years. Unfortunately, its mechanisms of action are not well understood, and controversy regarding its clinical efficacy remains. Importantly, acupuncture needling often evokes complex somatosensory sensations and may modulate the cognitive/affective perception of pain, suggesting that many effects are supported by the brain and extending central nervous system (CNS) networks. Modern neuroimaging techniques such as functional magnetic resonance imaging, positron emission tomography, electroencephalography, and magnetoencephalography provide a means to safely monitor brain activity in humans and may be used to help map the neurophysiological correlates of acupuncture. In this review, we will summarize data from acupuncture neuroimaging research and discuss how these findings contribute to current hypotheses of acupuncture action.
Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first through fourth digits. We hypothesize that aberrant afferent input from CTS will lead to maladaptive cortical plasticity, which may be corrected by appropriate therapy. Functional MRI (fMRI) scanning and clinical testing was performed on CTS patients at baseline and after 5 weeks of acupuncture treatment. As a control, healthy adults were also tested 5 weeks apart. During fMRI, sensory stimulation was performed for median nerve innervated digit 2 (D2) and digit 3 (D3), and ulnar nerve innervated digit 5 (D5). Surface-based and region of interest (ROI)-based analyses demonstrated that while the extent of fMRI activity in contralateral Brodmann Area 1 (BA 1) and BA 4 was increased in CTS compared to healthy adults, after acupuncture there was a significant decrease in contralateral BA 1 (P < 0.005) and BA 4 (P < 0.05) activity during D3 sensory stimulation. Healthy adults demonstrated no significant test-retest differences for any digit tested. While D3/D2 separation was contracted or blurred in CTS patients compared to healthy adults, the D2 SI representation shifted laterally after acupuncture treatment, leading to increased D3/D2 separation. Increasing D3/D2 separation correlated with decreasing paresthesias in CTS patients (P < 0.05). As CTS-induced paresthesias constitute diffuse, synchronized, multidigit symptomatology, our results for maladaptive change and correction are consistent with Hebbian plasticity mechanisms. Acupuncture, a somatosensory conditioning stimulus, shows promise in inducing beneficial cortical plasticity manifested by more focused digital representations.
Group data analysis in brainstem neuroimaging is predicated on accurate co-registration of anatomy. As the brainstem is comprised of many functionally heterogeneous nuclei densely situated adjacent to one another, relatively small errors in co-registration can manifest in increased variance or decreased sensitivity (or significance) in detecting activations. We have devised a 2-stage automated, reference mask guided registration technique (Automated Brainstem Co-registration, or ABC) for improved brainstem co-registration. Our approach utilized a brainstem mask dataset to weight an automated co-registration cost function. Our method was validated through measurement of RMS error at 12 manually defined landmarks. These landmarks were also used as guides for a secondary manual co-registration option, intended for outlier individuals that may not adequately co-register with our automated method. Our methodology was tested on 10 healthy human subjects and compared to traditional co-registration techniques (Talairach transform and automated affine transform to the MNI-152 template). We found that ABC had a significantly lower mean RMS error (1.22 +/- 0.39 mm) than Talairach transform (2.88 +/- 1.22 mm, mu +/- sigma) and the global affine (3.26 +/- 0.81 mm) method. Improved accuracy was also found for our manual-landmark-guided option (1.51 +/- 0.43 mm). Visualizing individual brainstem borders demonstrated more consistent and uniform overlap for ABC compared to traditional global co-registration techniques. Improved robustness (lower susceptibility to outliers) was demonstrated with ABC through lower inter-subject RMS error variance compared with traditional co-registration methods. The use of easily available and validated tools (AFNI and FSL) for this method should ease adoption by other investigators interested in brainstem data group analysis.
The ability to resolve complex fiber populations in muscular tissues is important for relating tissue structure with mechanical function. To address this issue in the case of tongue, we employed diffusion spectrum imaging (DSI), an MRI method for determining three-dimensional myoarchitecture where myofiber populations are variably aligned. By specifically varying gradient field strength, molecular displacement in a tissue can be determined by Fourier-transforming the echo intensity against gradient strength at fixed gradient pulse spacing. The displacement profiles are visualized by graphing three-dimensional isocontour icons for each voxel, with the isocontour shape and size representing the magnitude and direction of the constituting fiber populations. To validate this method, we simulated a DSI experiment within the constraints of arbitrary crossing fibers, and determined that DSI accurately depicts the angular relationships between these fibers. Considering the fiber relationships in the whole bovine tongue, we compared the images obtained by DSI with those obtained by diffusion tensor imaging in an anterior slice of the lingual core, a region known to possess extensive fiber crossing. In contrast to diffusion tensor imaging, which depicts the anterior core solely as a region with low anisotropy due to the presence of mixed-orientation fiber populations, DSI shows two distinct fiber populations, with an explicit orthogonal relationship to each other. In imaging the whole lingual tissue, we discerned arrays of crossing and noncrossing fibers involving the intrinsic and extrinsic muscles, which merged at regions of interface. We conclude that DSI has the capacity to determine three-dimensional fiber orientation in structurally complex muscular tissues.
The "Neurobiological Correlates of Acupuncture" Conference was convened November 17-18, 2005 in Bethesda, Maryland. The conference was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). Its goals were to encourage exchange of ideas regarding the direction of neuroimaging in acupuncture research as well as to discuss some of the challenges in this field. The use of neuroimaging, a relatively recent advance in the study of acupuncture, holds the promise of localizing and characterizing brain activity associated with acupuncture interventions in real time and in a minimally invasive way. Among the main challenges to research into the biological mechanisms of acupuncture are the multiple treatment variables and the difficulties of selecting appropriate experimental controls. Despite these challenges, numerous findings from acupuncture neuroimaging experiments were presented and discussed at the conference on topics related to possible signaling networks, sham acupuncture controls, acupoint specificity, acupuncture analgesia, acupuncture-associated brain response, and the potential for using neuroimaging in conjunction with translational and clinical acupuncture research. Future directions in acupuncture neuroimaging research, as recommended by conference participants, should focus on (1) continuing exploration of acupuncture signaling networks; (2) establishing standards and recommendations for performing and reporting acupuncture neuroimaging results; (3) enabling data sharing in the acupuncture neuroimaging community; (4) gaining a better understanding of placebo and control groups in acupuncture neuroimaging experiments; and (5) developing biomarkers that relate to physiologically and/or clinically relevant acupuncture responses to neuroimaging results.
Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first, second, and third digits. We hypothesize that aberrant afferent input in CTS will lead to cortical plasticity. Functional MRI (fMRI) and neurophysiological testing were performed on CTS patients and healthy adults. Median nerve innervated digit 2 (D2), and digit 3 (D3) and ulnar nerve innervated digit 5 (D5) were stimulated during fMRI. Surface-based and ROI-based analyses consistently demonstrated more extensive and stronger contralateral sensorimotor cortical representations of D2 and D3 for CTS patients as compared to healthy adults (P < 0.05). Differences were less profound for D5. Moreover, D3 fMRI activation in both the contralateral SI and motor cortex correlated positively with the D3 sensory conduction latency. Analysis of somatotopy suggested that contralateral SI representations for D2 and D3 were less separated for CTS patients (3.8 +/- 1.0 mm) than for healthy adults (7.5 +/- 1.2 mm). Furthermore, the D3/D2 separation distance correlated negatively with D2 sensory conduction latency-the greater the latency, the closer the D2/D3 cortical representations (r = -0.79, P < 0.05). Coupled with a greater extent of SI representation for these CTS affected digits, the closer cortical representations can be interpreted as a blurred somatotopic arrangement for CTS affected digits. These findings provide further evidence that CTS is not manifest in the periphery alone. Our results are consistent with Hebbian plasticity mechanisms, as our cohort of CTS patients had predominant paresthesias, which produce more temporally coherent afferent signaling from affected digits.
The anatomy of the mammalian tongue consists of an intricate array of variably aligned and extensively interwoven muscle fibers. As a result, it is particularly difficult to resolve the relationship between the tongue's microscopic anatomy and tissue-scale mechanical function. In order to address this question, we employed a method, diffusion spectrum imaging (DSI) with tractography, for displaying the macroscopic orientational properties of the tissue's constituting myofibers. DSI measures spatially variant proton displacement for a given 3D imaging segment (voxel), reflecting the principal orientation(s) of its myofibers. Tractography uses the angular similarity displayed by the principal fiber populations of multiple adjacent voxels to generate tract-like structures. DSI with tractography thus defines a unique set of tracts based on the net orientational behavior of the myofiber populations at different positions in the tissue. By this approach, we demonstrate a novel myoarchitectural pattern for the bovine tongue, consisting of short and orthogonally aligned crossing fiber tracts in the intrinsic core region, and longer, parallel-aligned fiber tracts on the tissue margins and in the regions of extrinsic fiber insertion. The identification of locally aligned myofiber populations by DSI with tractography allows us to reconsider lingual anatomy, not in conventional microscopic terms, but as a set of heterogeneously aligned and macroscopically resolved myofiber tracts. We postulate that the properties associated with these myofiber tracts predict the mechanical behavior of the tissue and thus constitute a method to relate structure and function for anatomically complex muscular tissues.
Past neuroimaging studies of acupuncture have demonstrated variable results for important brainstem nuclei. We have employed cardiac-gated fMRI with T1-variability correction to study the processing of acupuncture by the human brain. Furthermore, our imaging experiments collected simultaneous ECG data in order to correlate heart rate variability (HRV) with fMRI signal intensity. Subjects experienced one of three stimulations over a 31.5 minute fMRI run: (1) electro-acupuncture at 2Hz/15Hz over the acupoint ST-36 (2) electro-acupuncture at a sham non-acupoint, or (3) sensory control tapping over ST-36. The ECG was analyzed with power spectral methods for low frequency and high frequency components, which reflect the balance in the autonomic nervous system. The HRV data was then correlated with the time-varying fMRI signal intensity. Our data suggests that fMRI activity in the hypothalamus, the dorsal raphe nucleus, the periaqueductal gray, and the rostroventral medulla showed significant correlation with LF/HF ratio calculated from simultaneous HRV data. The correlation of time-varying fMRI response with physiological parameters may provide insight into connections between acupuncture modulation of the autonomic nervous system and neuroprocessing.
The goal of this functional magnetic resonance imaging (fMRI) study was to compare the central effects of electroacupuncture at different frequencies with traditional Chinese manual acupuncture. Although not as time-tested as manual acupuncture, electroacupuncture does have the advantage of setting stimulation frequency and intensity objectively and quantifiably. Manual acupuncture, electroacupuncture at 2 Hz and 100 Hz, and tactile control stimulation were carried out at acupoint ST-36. Overall, electroacupuncture (particularly at low frequency) produced more widespread fMRI signal increase than manual acupuncture did, and all acupuncture stimulations produced more widespread responses than did our placebo-like tactile control stimulation. Acupuncture produced hemodynamic signal increase in the anterior insula, and decrease in limbic and paralimbic structures including the amygdala, anterior hippocampus, and the cortices of the subgenual and retrosplenial cingulate, ventromedial prefrontal cortex, frontal, and temporal poles, results not seen for tactile control stimulation. Only electroacupuncture produced significant signal increase in the anterior middle cingulate cortex, whereas 2-Hz electroacupuncture produced signal increase in the pontine raphe area. All forms of stimulation (acupuncture and control) produced signal increase in SII. These findings support a hypothesis that the limbic system is central to acupuncture effect regardless of specific acupuncture modality, although some differences do exist in the underlying neurobiologic mechanisms for these modalities, and may aid in optimizing their future usage in clinical applications.
Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.
The myoarchitecture of the tongue is believed to consist of a complex network of interwoven fibers, which function together to produce a near limitless array of functional deformations. These deformations contribute mechanically to speech production and to oral cavity food handling during swallowing. We have previously imaged the 3D myoarchitecture of the mammalian tongue in excised tissue with diffusion tensor MRI, a technique which derives the 3D orientation of intramural fibers as a function of the extent to which a direction-specific MR signal attenuates under diffusion-encoding magnetic gradients. The resulting 3D diffusion tensor defines the relative orientations of the myofiber populations within a region of tissue. In this study, we have extended the use of this method to assess lingual myoarchitecture in normal human subjects in vivo. Subjects were imaged using a diffusion-sensitive stimulated-echo pulse sequence with single-shot echo-planar spatial encoding in the midsagittal plane. Differences in lingual fiber orientation were manifested by graduated changes in fiber direction throughout the tissue, without clear anatomical demarcations between regions of the tissue. The anterior tissue was composed generally of orthogonally oriented fibers surrounded by an axially oriented ring of tissue, whereas the posterior portion of the tissue was composed mostly of fibers projecting in the superior and posterior directions. The bulk of the tissue displayed a highly homogeneous, vertically oriented set of fibers, including the anteroinferior region of the tissue and extending nearly to the superior surface. Further analysis of the tissue in terms of diffusion anisotropy demonstrated that the tissue could be represented by varying degrees of anisotropy, with a tendency toward high anisotropy in the dorsal and anteroventral periphery and low anisotropy in the central region of the tissue. These findings demonstrate that the muscular anatomy of the tongue can be displayed as a continuous array of structural units, or tensors, representing fibers of varying orientations throughout the tissue.
OBJECTIVES: This study quantifies and compares patient characteristics in outpatient acupuncture.
SETTING/DESIGN: Prospective primary source evidence was gathered at two prominent outpatient acupuncture clinics in Beijing, China (n = 563, n = 233).
RESULTS: The most common condition was Bell's palsy, which represented 20.6% and 25.3% of total cases at the two clinics, respectively. The second most common condition was cerebrovascular accident (CVA) rehabilitation. These treatments represented 11.9% and 12.0% of treatments at the two clinics, respectively. Other trends at the clinics included the following: (1) neurologic complaints predominated; (2) doctors see a large number of patients per day; (3) the majority of patients overall were female; while (4) the majority of patients treated for CVAs rehabilitation were male. As cultural and socioeconomic differences in perceptions of acupuncture exist between peoples of different countries, this study also compared patient main complaints in China to available data on acupuncture patients seen in other parts of China, Germany, the United Kingdom, Australia, and the United States. Except for the German clinic data, Western clinic acupuncturists saw more musculoskeletal complaints compared to China, where neurologic complaints predominated. Another significant difference between Asian and Western clinics was the number of patients seen per hour. While acupuncturists were reported to see 1.2 patients per hour in U. S. clinics, acupuncturists at the two Beijing, China, clinics saw 7.0 and 10.4 patients per hour, respectively.
CONCLUSION: The main complaints seen in acupuncture outpatient clinics throughout the world likely result from a combination of inherent disease prevalence as well as patients' attitudes toward what acupuncture can treat successfully.
Acupuncture textbooks mention a wide assortment of indications for each acupuncture point and, conversely, each disease or indication can be treated by a wide assortment of acupoints. However, little systematic information exists on how acupuncture is actually used in practice: i.e. which points are actually selected and for which conditions. This study prospectively gathered data on acupuncture point usage in two primarily acupuncture hospital clinics in Beijing, China. Of the more than 150 unique acupoints, the 30 most commonly used points represented 68% of the total number of acupoints needled at the first clinic, and 63% of points needled at the second clinic. While acupuncturists use a similar set of most prevalent points, such as LI-4 (used in >65% of treatments at both clinic sites), this core of points only partially overlaps. These results support the hypothesis that while the most commonly used points are similar from one acupuncturist to another, each practitioner tends to have certain acupoints, which are favorites as core points or to round out the point prescription. In addition, the results of this study are consistent with the recent development of "manualized" protocols in randomized controlled trials of acupuncture where a fixed set of acupoints are augmented depending on individualized signs and symptoms (TCM patterns).