acupuncture/herbal medicine/shiatsu

                           Mechanisms of Acupuncture

 

I would like to paint you a picture, tell the story ~

how acupuncture works from needle insertion to beneficial physiological effect: 

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1) connective tissue stimulation/mechanotransduction/cellular remodeling; 

2) molecular and genetic/biochemical cascades;

3) nervous system responses, regional brain responses, immune responses, endocrine responses

4) beneficial physiological/musculoskeletal impact

5) progressive accumulation of impact over time

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Connective Tissue

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Liddle CE, Harris RE. Cellular reorganization plays a vital role. Med Acupunct. 2018;30(1). DOI: 10.1089/acu.2017.1258 in Acupuncture Analgesia

 

Researchers Liddle and Harris (2018) performed a review of literature involving the mechanism of acupuncture analgesia. They found research to support the understanding that connective tissue winding around acupuncture needles initiates mechanotransduction, cytoskeletal rearrangement, and extracellular matrix rearrangement, which stimulates downstream cellular responses, including biochemical, molecular, and genetic expression pathways. They found evidence of greater density of connective tissue at acupuncture point locations. Research demonstrated that the direction of needle rotation or type of needle stimulation affects how much connective tissue winding takes place. Connective tissue winding initiates cytoskeletal remodeling and shape change via mechanotransduction. Needle insertion pulls on “​​collagen–cell adhesion junctions,” a process in which fibroblasts flatten and cell surface-area increases. Researchers believe that fibroblasts continue to communicate with each other down the connective tissue matrix like a wave involving mechanical and molecular signals. Research has demonstrated that “cytoskeletal rearrangement has been linked to cellular migration and protein synthesis.” Protein synthesis is understood in general cellular biology to be a response to genetic signaling. Connective tissue winding and cellular shape change elicit signal transduction in cells connected to the collagen in that area, including mast cells. Mast cells, which are involved in immune and neuroimmune responses, and similar cells, are located in more abundance near acupuncture points and are stimulated by needling to release histamine. Based on the evidence, researchers believe that cellular remodeling is the most crucial macro-factor involved with reduced inflammation and pain near acupuncture sites. Connective tissue density, morphology, cross-linking, and remodeling are cited as areas for future research. Determining mechanism and the necessary technique to properly achieve connective tissue stimulation could lead to more accurate assessments of potential benefits and to improved patient care. 

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Bianco G. Fascial neuromodulation: an emerging concept linking acupuncture, fasciology, osteopathy and neuroscience. Eur J Transl Myol. 2019;29(3):195-201.

 

Bianco reviewed the topics of acupuncture and neuroscience, fascial network hypotheses, fascial neuromodulation, and the influences of stress and posture on fascial connective tissue and neuromodulation. The author stated that connective tissue models of the mechanism of acupuncture are compatible with both ancient models and with neurophysiological explanations. Although acupuncture has neurophysiological effects, the author provided evidence against the nervous system as being the underlying unifying mechanism of acupuncture: “​​Different functional magnetic resonance imaging (fMRI) activation pattern[s] in the brain induced by stimulation of different acupoints in the same spinal segment, while acupoints on the same “channel” had shown similar activation/deactivation patterns, although non belonging to the same spinal segment.” The author concluded that the neurophysiological model for the mechanism of acupuncture is only a partial explanation, while the connective tissue/fascia model is a more complete, integrated, and useful model. 

 

Langevin HM, Schnyer RN. Reconnecting the body in eastern and western medicine. J Altern Complement Med. 2017;23(4):238-241. DOI: 10.1089/acm.2017.0028

 

In alignment with Chinese medicine’s understanding of the body as a dynamic moving, transforming, and changing whole, the concept of connective tissue as a bridge that connects and communicates with whole-body physiology fills previous gaps in knowledge of the body. “The ancient Chinese concept of a diffuse, web-like matrix permeating and connecting all parts and components of the body resonates well [with] the modern understanding of matrix biology and the emerging view of the body as an integrated system.” Systems biology helps western scientists to think in terms of a unified physical body, and the emergence of the fields of mechanobiology and mechanotherapeutics reintegrate physics into microsystem views of the body. The connective tissue theory is supported in the way classical texts describe acupuncture, aligns with the practice of many acupuncturists who use channel palpation and physical tissue characteristics (hollow, dense, stiff, hot, cold) to guide treatment, and is supported by a growing evidence base.  

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Bai Y, Wang J, Wu J, Dai J, Sha O, Yew DTW, Yuan L, Liang Q. Review of evidence suggesting that the fascia network could be the anatomical basis for acupoints and meridians in the human body. Evid Based Complement Altern Med. 2011;2011:260510. DOI:10.1155/2011/260510

 

Abstract of paper: “The anatomical basis for the concept of meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the evidence supporting a relationship between acupuncture points/meridians and fascia. The reviewed evidence supports the view that the human body’s fascia network may be the physical substrate represented by the meridians of TCM. Specifically, this hypothesis is supported by anatomical observations of body scan data demonstrating that the fascia network resembles the theoretical meridian system in salient ways, as well as physiological, histological, and clinical observations. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.”

 

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Schleip R, Zorn A, Klingler W. Biomechanical properties of fascial tissues and their role as pain generators. J Musculoskelet Pain. 2010;18(4). DOI: 10.3109/10582452.2010.502628

 

This review covered the importance of fascial connective tissue in load-bearing and susceptibility to microtearing. Simply put, “fascial tissues serve important load-bearing functions.” For example, researchers have found that muscles transmit force to lateral tissues via epimysia, the fibrous tissue envelope that surrounds skeletal muscle. During forward bends, dorsal fascia exhibit “strong tensional load-bearing,” which is lacking in low back pain patients. In addition, during oscillatory movements such as walking, hopping, or running,  researchers have found that fascia act as “elastic springs,” supporting the isometric contraction of skeletal muscles. Fascia have been shown to undergo viscoelastic deformation and microtearing due to severe tensional load-bearing. These microtears and ensuing inflammation “can be a direct source of musculoskeletal pain.” Fascial connective tissue is also “densely innervated by myelinated nerve endings” such as Pacini’s [and paciniform] corpuscles, Golgi tendon organs, and Ruffini endings) and free nerve endings (some that release substance-P), indicating a “nociceptive function.” Additionally, fascial microtrauma, inflammation, and thickening has been shown to contribute indirectly to low back pain and may do so by activating the meshwork of nerve endings found within fascial tissue. 

 

Langevin H, Bouffard NA, Churchill DL, Badger GJ. Connective Tissue Fibroblast Response to Acupuncture: Dose-Dependent Effect of Bidirectional Needle Rotation. JACM. 2007;13(3):355–360. DOI: 10.1089/acm.2007.6351

 

Background: At the time of publication in 2007, there was not much information about the effects of various acupuncture needling manipulation techniques.

 

Objectives: The researchers who performed this study hypothesized that “bidirectional acupuncture needle rotation cause[d] dose-dependent active cytoskeletal remodeling in connective tissue fibroblasts,” as had already been demonstrated for unidirectional needle rotation. 

 

Interventions: Needle rotation cycles of 8-64 and rotation-cycle amplitude (180-720 degrees) were used on subcutaneous mouse tissue explants for 30 minutes each. The tissues were then histologically fixed, examined via confocal microscopy, and the fibroblast cell cross-sectional areas were measured. 

 

Results: Fibroblasts responded to bidirectional needle rotation as they had to unidirectional rotation - “with extensive cell spreading and lamellipodia formation.” ANOVA was used to examine the results. There was a statistically significant increase in fibroblast cell body cross sectional area (p<0.001). Cells exhibited greater cellular responses to specific windows of amplitude and numbers of needle rotation cycles. 

 

Conclusions: Acupuncture needle manipulation techniques affect cellular responses within mouse subcutaneous tissue. The researchers plan to study the connection between connective-tissue remodeling and therapeutic effects in the future.

 

Langevin HM, Bouffard NA, Badger GJ, Churchill DL, Howe AK. Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: Evidence for a mechanotransduction-based mechanism. J Cell Physiol. 2006;207:767–774.  

 

Previous studies have demonstrated that acupuncture needle rotation elicited cytoskeletal remodeling in subcutaneous connective tissue. Prior research also demonstrated that “the cytoskeleton is an integrated and dynamic system within the cell that actively interacts with the extracellular matrix via specialized sites on the cell surface.” In this study, external mechanical force of computer-controlled unidirectional acupuncture needle rotation was applied to mouse subcutaneous tissue. Cellular changes in tissue shape variation for the needled tissue and tissue directly lateral to needle insertion were analyzed using confocal microscopy. Preload impact upon cellular changes was first analyzed to establish a baseline; 2.9nM was chosen as the preload, as “cross-sectional area did not significantly change until 4.9nM was applied to the tissue.” Two-way ANOVA and Fisher’s LSD were used to analyze the data. Results showed that unidirectional needle rotation “induced extensive fibroblast spreading and lamellipodia formation within 30 min[utes], measurable as an increase in cell body cross sectional area.” Lack of needle rotation resulted in uniform fibroblast morphology - no morphological changes. The  morphological effects reached maximum at two needle revolutions and decreased with continued rotation. The effects of needle rotation extended throughout the tissue samples laterally several centimeters away from the needling locations. Needling rotation effects could be halted by introducing pharmacological actomyosin contraction inhibitors. These results demonstrated an “active cytoskeletal response of fibroblasts,” and support the connective tissue mechanotransduction model for the mechanism of acupuncture.

 

Researchers theorize the following sequence of events involved with acupuncture needle insertion and subsequent cellular changes: “(1) winding and pulling of tissue from the periphery toward the needle; (2) initial pull of extracellular matrix on fibroblasts at existing focal contacts; (3) formation of lamellipodia (Rac-induced) in regions of the cell that are mechanically stimulated (predominantly in the plane of the pulled tissue); (4) increased actomyosin contraction (Rho-induced) with-out distinct stress fiber formation (due to the complex three-dimensional pattern of matrix attachments); (5) microtubule migration and stabilization; (6) increased intracellular tension, cell expansion, and flattening in the tissue plane until a new tension equilibrium is achieved between intracellular tension (actomyosin-driven) and two types of opposing forces: (a) extracellular matrix counter-tensional forces and (b) intracellular compressive forces provided by the expanded cytoskeleton."

 

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Ahn AC, Wu J, Badger GJ, Hammerschlag R, Langevin HM. Electrical impedance along connective tissue planes associated with acupuncture meridians. BMC Complement Altern Med. 2005;5:10. DOI:10.1186/1472-6882-5-102005

 

Researchers sought to demonstrate whether electrical conductance differences exist along acupuncture meridian connective tissue versus non-acupuncture meridian connective tissue. Prior studies have shown such evidence, but the studies were flawed in ways that this study sought to ameliorate, including the use of surface electrodes versus inserted needles. Twenty-three human subjects participated in this study. Four gold plated needles inserted in a straight row on Spleen and Pericardium meridians to a depth of 10mm and a control series of needles were inserted 0.8 cm medial to these. An impedance meter was used that transmitted a 3.3 kHz alternating current at three amplitudes (20, 40, and 80 μAmps) between the two outer needles. Within the impedance meter was a current meter that measured current between the two outer needles, and a voltage meter that measured voltage between the two inner needles. The needles themselves served as electrodes. “Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity).” During this process, an ultrasound scanner depicted underlying connective tissue. Tissue impedance was significantly lower on the Pericardium meridian compared to the control (p = 0.0003), but not for the Spleen meridian (p = 0.70). The Pericardium meridian needles displayed greater contact with the connective tissue, as displayed by ultrasound imaging. Researchers postulated that lower impedance may result from needle contact with underlying connective tissue. In clinical settings, the Spleen meridian may need to be needled deeper than 10mm to gain contact with the connective tissue and therefore greater electrical conductivity. In general, researchers have suggested that the collagen in connective tissue may be conductive or that connective tissue matrix serves as a conductive media for electrical signals. “Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue.”

 

Langevin HM, Konofagou EE, Badger GJ, Churchill DL, Fox JR, Ophir J, Garra BS. Tissue displacement during acupuncture using ultrasound elastography techniques. Ultrasound Med Biol. 2004;30(9):1173–1183. DOI:10.1016/j.ultrasmedbio.2004.07.010

 

Researchers identified the effects of needle manipulation as an overlooked factor in previous acupuncture studies. It is hypothesized tissue displacement as a result of insertion and manipulation of acupuncture needles is one of the biomechanical mechanisms for acupuncture.  This study sought to quantify and measure tissue displacement during acupuncture in human models. In vivo ultrasound techniques were used to map spatial and temporal tissue behavior during needle manipulation. Twelve human subjects were included in the study. A computerized controlled machine was used to insert and manipulate acupuncture needles into each participant's thigh, ultrasound was then used to measure tissue displacement. It was found that rotation of the needle had significant linear effects on tissue displacement during downward and upward needle motion. It is theorized that rotation increases the mechanical bond between the connective tissue and the needle increasing the necessary force to remove the needle from the skin or muscle. It is theorized this mechanical stimulation and displacement of connective tissue creates the spreading of effects across the tissue and generates a therapeutic effect. This study recommends more quantitative data should be collected to understand mechanisms of acupuncture and improve technique.  

 

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Langevin HM, Churchill DL, Wu J, Badger GJ, Yandow JA, Foxá JR, Kragá MH. Evidence of connective tissue involvement in acupuncture. FASEBJ. 2002. DOI:10.1096/fj.01-0925fje. Published online April 10, 2002.

 

This 3-part study sought to answer the question of whether acupuncture needle rotation resulting in a “needle grasp” was due to the contraction of the muscle that the needle was inserted into or whether it was due to contraction of the subcutaneous connective tissue. “Needle grasp” causes the needle to require more force to remove it, and the researchers were able to standardize the needle depth, retention, and rotation as well as measure the force required to remove the needle by using a robotic needling instrument. The human component of the study measured the force required to pull the needle out of a more muscular area (a site lateral to the lumbar spine) versus the force required to pull the needle out of the sacral area, which has deep subcutaneous connective tissue rather than muscle. Needles were inserted in both areas randomly to 2 different depths, with either unidirectional rotation, bi-directional rotation, or no rotation. The pullout force needed to extract needles with unidirectional rotation from deeper in subcutaneous connective tissue was much greater than that needed to extract needles inserted deeper into the muscle tissue.

 

The 2nd part of the experiment was performed on rats in vivo. These experiments measured pullout force and used histology to note changes in tissue density that came with unidirectional rotation of acupuncture needles versus no rotation. Again, the pullout force needed for needles rotated unidirectionally was greater than that required to extract a needle without rotation. Histological analysis showed that connective tissue around the rotated needle was denser than in tissue where the needle had not been rotated.

 

The 3rd part of the experiment was performed on rats in vitro. Ultrasound imaging was performed on tissue where acupuncture needles were rotated and not rotated. The imaging of tissues around areas of unidirectional needle rotation showed a distinctive spiral pattern that was missing in tissues without rotation. 

 

The authors state: “Pulling of collagen and/or elastic fibers and deformation of extracellular matrix during needle manipulation may have powerful and long-lasting effects on local cells, including synthesis and release of extracellular matrix components and modification

of interstitial connective tissue composition.” Together, these studies show that acupuncture needle stimulation has a measurable mechanical effect on connective tissue, in addition to previously discovered therapeutic effects on the nervous system.

 

Langevin HM, Churchill DL, Cipolla MJ. Mechanical signaling through connective tissue: A mechanism for the therapeutic effect of acupuncture. FASEB. 2001;15:2275-2282.

The authors of this study proposed a comprehensive connective tissue model/mechanism for acupuncture that was strongly supported with evidence. The authors proposed that the phenomenon of “needle grasp” (the achievement of ‘de qi’) was due connective tissue wrapping around the needle upon insertion/rotation and that the resulting mechanotransduction signals a cascade of downstream events.  The authors believe that this mechanism can explain the local, distal, and long-term effects of acupuncture. The methods included use of rat abdominal wall tissue explants to examine histological changes associated with needle insertion and manipulation. Five minutes after excision a 0.25 Seirin needle was inserted into the tissue sample and either rotated 32 times unidirectionally or not rotated at all. After one minute, the tissue samples were placed in formalin and then paraffin. These were sliced parallel to needle direction and processed for histological analysis. The results of histological observation included thickened connective tissue surrounding the needle, with no observable changes to the muscle tissue layers. Masson trichrome staining elucidated collagen winding around the needle. Pullout force was shown to increase with connective tissue winding. Connective tissue collagen fibers in rat tissue samples were also observed to be “straighter and more nearly parallel to each other after needle rotation.” Fibroblasts within connective tissue attach to collagen at focal adhesion complexes; these fibroblasts become aligned with the connective tissue, change shape from rounded to flat, and develop more polymerized actin after acupuncture needle insertion and rotation. These observations were all consistent with the hypothesis of needle-tissue coupling leading to mechanotransduction via extracellular matrix deformation, stimulating a complex downstream cascade of molecular and biochemical pathways, a truly systemic impact. The sequence of events includes collagen winding, matrix deformation, mechanotransduction, protein phosphorylation by mitogen-activated protein kinases (MAPKs), gene expression leading to protein synthesis and secretion, biochemical modification of proteins within the extracellular matrix, and effects such as neuromodulation and mast cell activation. Actin polymerization and cell contraction following mechanotransduction acts as a ripple effect, continuing the wave of deformation and mechanotransduction.

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