Key to an Age-Old Mystery? Effects of Acupuncture Needle Manipulation on Connective Tissue Matrix

Not a week goes by that one of my patients doesn’t query me about “how acupuncture works.” It is natural and reasonable for someone to want to know what’s about to happen when a health care professional has them lie down on a treatment table and then proceeds to insert fine needles at various loci on their body. Of course, they also want to know if it will hurt. (It doesn’t.)

Well, good news on the how-it-works front: Recent research into the technique of acupuncture needle manipulation has begun to shed some light on at least one possible mechanism of action by which acupuncture relieves pain.
Helene M. Langevin is a visiting professor of medicine and Director of the Osher Center for Integrative Medicine at Brigham and Women’s Hospital, Harvard Medical School, and a professor of neurological sciences at the University of Vermont notes that connective tissue, one of the most integral components of the human body with an increasingly evident role in chronic pain and other diseases, is not very well studied.

Connective tissue surrounds nerves, blood vessels and lymphatics. Dr. Langevin has begun to explore an intriguing relationship between acupuncture, acupuncture meridian pathways (jing luo) and connective tissue response.
In particular, she has investigated the “twirling,” of the needle, one of several standard methods of needle manipulation performed by licensed acupuncturists. Acupuncturists utilize this technique to obtain “de qi,” the arrival of the qi sensation. In fact, this sensation can vary among individuals; some feel it strongly, others more weakly. This variation, in turn, is often a function of the practitioner’s degree of needle manipulation and whether the acupuncturist even thinks it clinically appropriate to utilize much needle manipulation for a given patient or during a given patient’s course of treatment.

To the patient, the qi sensation can feel like expanding warmth (either at or distal to the needling site), needles-and-pins, a heavy dull ache, or other sensations. A smaller percentage of patients might experience needle sensation propagation, whereby the qi sensation is felt by the patient quite far away from its insertion site. For example, I recently needled a patient at zusanli point lateral to the tibia. This point lies along the Stomach meridian and is interiorly-exteriorly related to (i.e., links to) the Large Intestine meridian. The patient expressed a clear sensation in the region of Jianyu point, at the anterior (frontal) aspect of her shoulder.

 [IMAGE] During acupuncture needle insertion, the patient’s qi sensation is often transmitted as a grab or tugging at the practitioner’s end of the needle. This has traditionally been described as roughly akin to when a fish gets caught on a hook. Occasionally, removal of a needle can result in minor ecchymosis (non-raised skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels) or even a small hematoma (sort of a 3 dimensional ecchymosis). In such instances, I typically explain to the patient that the tissue has wrapped itself around the needle and “followed” the needle toward the superficial skin layer as it is removed. Recent biomedical research may support that explanation.

In her research, Dr. Langevin collaborated with Martin Krag, an orthopedic surgeon at University of Vermont College of Medicine who had some experience testing alternative-medicine approaches using scientific methods. With the help of David Churchill, a biomedical engineer in the Orthopedic Department at UVM who designed a robotic acupuncture-needling instrument, they measured the force needed to pull out the needles in a reproducible manner from 16 different points on the body. This “pullout force” did indeed increase after needle rotation, at times so dramatically that it exceeded the capacity of their 500 g load-measurement device.
1

Investigating the cause on rat tissue under microscope, they saw something striking: when acupuncture needles were rotated, the loose connective tissue under the skin became mechanically attached to the needle. Even a small amount of rotation caused the connective tissue to wrap around the needle, like spaghetti winding around a fork. This winding caused the surrounding connective tissue to become stretched as it was pulled by the needle’s motion. Using ultrasound, they confirmed that the same phenomenon occurs in live tissue 2.

Simulation of connective tissue matrix spooling around an acupuncture needle, creating a localized tissue stretch. The green blobs represent fibroblasts being pulled and stretched along with the connective tissue matrix.

From Langevin’s research, needled subcutaneous rat tissue observed under a microscope reveals that a visible “whorl” of tissue can be produced with as little as one turn of the needle (click for images). When the needle is placed flat onto the subcutaneous tissue surface and then rotated, the tissue tends to adhere to and follow the rotating needle for 180 degrees, at which point the tissue adheres to itself and further rotation results in formation of a whorl. Size and material of the needle seem to be important. Needles larger than 1 mm (typical acupuncture needles are very fine; 250–500 μm diameter), fail to produce the winding effect. Rougher needles (e.g., old style, autoclaved gold needles) seem to produce more “grab” than modern disposable stainless steel.


 [IMAGE] According to Dr. Langevin, interest in connective tissue among Western biomedical researches has been almost exclusively restricted to the tendons and ligaments that connect bone to muscles and to other bones, respectively. Non-specialized connective tissues, called fasciae and which surround and/or run through all muscles, nerves, bones, and blood vessels, were historically accorded only brief mention. In fact it is disciplines such as acupuncture, which includes the musculo-tendon pathways and the meridian system, as well as body-work systems such as myofascial release, Rolfing, and conventional physical therapy that have emphasized the role of fascia and tissue remodeling.

This is changing, however. Mechanotransduction studies how the integrin family of adhesion molecules forms a physical and informational link between the extracellular matrix and the interior of cells.

Through these cell-matrix connections, cells sense forces and transform these mechanical signals into cellular responses such as the activation or deactivation of signaling molecules, translocation of transcription factors into the nucleus, and ultimately, changes in gene expression 3. In addition, substantial evidence supports the notion that mechanical signals can be transmitted directly through the cytoskeleton (cellular scaffolding) into the interior of the nucleus.

Some of the most well-established work in this field has involved the study of fibroblasts. These cells are responsible for synthesizing the proteins that make up the extracellular matrix (the non-cellular component present within all tissues and organs that provides essential physical scaffolding for the cellular constituents and also initiates crucial biochemical and biomechanical cues that are required for tissue morphogenesis, differentiation and homeostasis). Fibroblasts reside within the matrix they create, responding to mechanical stimulation by regulating the amount of collagen and other matrix proteins produced, and by secreting matrix-degrading enzymes in response to chronic changes in tissue forces.

Such changes can be induced by repetitive motion and are thought to be an important factor in work-related musculoskeletal injuries such as tendinitis of the shoulder or wrist 4. Fibroblasts transform into myofibroblasts which play a major role in helping wounds to knit together and heal. Myofibroblasts secrete large amounts of collagen and special proteins and then apply tension on the collagen matrix, pulling the edges of the wound together. Myofibroblasts normally die once a stable scar has formed. But they may continue to deposit excessive collagen during chronic inflammation, resulting in increased tissue tension and restriction of normal range of motion.

Work with fibroblasts is beginning to influence clinical research. For example, large numbers of low back pain cases present no detectable abnormalities of the spine and associated tissues; the source of their pain seems unknown. Researchers at the University of Heidelberg found in 2008 that connective tissue contains sensory nerve endings that can transmit pain when stretched in the presence of inflammation 5. Dr. Langevin’s ultrasound studies demonstrated that the connective tissues that surround the muscles of the back are, on average, thicker in people with chronic low back pain 6 as well as a decreased gliding motion of dense layers, suggesting that a fibrotic process as a possible cause of decreased mobility.

In her research involving cellular response to acupuncture needle insertion, Dr. Langevin’s team observed that the fibroblasts residing in the connective tissue as far as several centimeters away from the needle began to reorganize their internal cytoskeleton and change shape, becoming large and flat. The same response can be observed by simply stretching the tissue for approximately 30 minutes, about the same time duration of needle retention during a typical acupuncture treatment. They also found that letting go of the needle after needle rotation does not cause the tissue to immediately unwind from the needle. The “whorl” of connective tissue remains intact as long as the needle remains under the skin, causing the tissue to be stretched for a prolonged period. Langevin’s team found that the tissue changes with acupuncture are associated with a large-scale relaxation of the connective tissue wherein fibroblasts initiated a specific Rho-dependent cytoskeletal reorganization that was required for full tissue relaxation. Rho is an intracellular signaling molecule known to play a role in cell motility and the remodeling of cell-surface proteins that connect the fibroblast to its surrounding matrix. They also found that the shape change is also associated with a sustained release of adenosine triphosptate (ATP) from the fibroblast 7. According to Dr. Langevin, ATP acts as fuel inside the cell, but outside of the cell membrane ATP can function as a signaling molecule. Extracellular ATP can be converted to other purines such as adenosine, which can act as a local analgesic, thus providing a possible cellular and physiological mechanism to explain the pain relief experienced by some acupuncture patients 8

Connection to Acupuncture Meridians

Acupuncture-needle manipulation results in sustained stretching, and therefore constitutes a useful tool that can be used to study the biomechanical functions described above. But how might all of this be explained from the perspective of traditional Chinese medicine?
  The table below is from Langevin and Landow (2002), published in the The Anatomical Record in December, 2002. It suggests a model describing certain acupuncture phenomena in terms of Western anatomy and physiology.

Summary of Proposed Model of Physiological Effects Seen in Acupuncture

Traditional Chinese Medicine Concepts
Proposed Anatomical/Physiological Equivalents
Acupuncture meridians
Connective tissue planes
Acupuncture points
Convergence of connective tissue planes
Qi
Sum of all body energetic phenomena (e.g., metabolism, movement, signaling, information exchange)
Meridian qi
Connective tissue biochemical / bioelectrical signaling
Blockage of qi (qi impediment)
Altered connective tissue matrix composition leading to altered signal transduction
Needle grasp
Tissue winding and / or contraction of fibroblasts surrounding the needle
De qi sensation (needle sensation)
Stimulation of connective tissue sensory mechanoreceptors
Propagated de qi sensation 
Wave of connective tissue contraction and sensory mechanoreceptor stimulation along connective tissue planes
Restoration of qi flow
Cellular activation / gene expression leading to restored connective tissue matrix composition and signal transduction

Early in their training, every acupuncturist learns about the 12 primary acupuncture channels, the channel divergents, and the tendino-muscle pathways (jin mai, jin jing). The tendino-muscle pathways are a channel network that circulates qi over the superficial aspect of the body and, unlike the 12 primary channels, do not penetrate to the zang fu (internal organs). Said to travel in the “depressions and planes between muscles and tendons” 9 , along with Wei qi (defensive qi), the tendino-muscle meridians follow the lines of major muscles and muscle groups, tendons, ligaments, and fascia. In addition to circulating throughout the superficial layers of body tissue, Wei qi is not contained within a vessel. Its path is, therefore, broad and diffuse.

The Jing (well) points are the only acupuncture points directly shared by both the primary meridians and the tendino-muscle pathways. These are located on the fingers and toes of the four extremities.

In research, of course, one must be careful to avoid the issue of finding only what one looks for. Interestingly, Dr. Langevin notes that acupuncture points seem to be preferentially located along connective-tissue planes between muscles, or between muscle and bone, finding that more than 80 percent of acupuncture points in the arm are located along connective-tissue planes
10 .  Loose connective tissue contains blood vessels and nerves. Mechanical stimulation of connective tissue by acupuncture needle manipulation could transmit a mechanical signal to sensory nerves, as well as intrinsic sensory afferents directly innervating connective tissue. According to traditional Chinese medicine, however, certain of the acupuncture points (e.g., xi cleft points), run deeply to the internal organs and thus are, theoretically, able to influence disease and illness beyond superficial musculoskeletal problems.

References:
1. H.M. Langevin et al., “Biomechanical response to acupuncture needling in humans,” J Appl Physiol, 91:2471-78, 2001.
2. H.M. Langevin et al., “Tissue displacements during acupuncture using ultrasound elastography techniques,” Ultrasound Med Biol, 30:1173-83, 2004.
3. A. Mammoto et al., “Mechanosensitive mechanisms in transcriptional regulation,” J Cell Sci, 125:3061-73, 2012.
4. S.M. Abdelmagid et al., “Performance of repetitive tasks induces decreased grip strength and increased fibrogenic proteins in skeletal muscle: role of force and inflammation,” PLOS ONE, 7:e38359, 2012.
5. T. Taguchi et al., “Dorsal horn neurons having input from low back structures in rats,” Pain, 138:119-29, 2008
6. H.M. Langevin et al., “Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain,” BMC Musculoskelet Disord, 10:151, 2009.
7. H.M. Langevin et al., “Fibroblast cytoskeletal remodeling contributes to connective tissue tension,” J Cell Physiol, 226:1166-75, 2011.
8. N. Goldman et al., “Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture,” Nat Neurosci, 13:883–88, 2010.
9. Reaves, Whitfield, The Acupuncture Handbook of Sports Injuries and Pain. Hidden Needles Press, Boulder, 2009
10. H.M. Langevin, J.A. Yandow, “Relationship of acupuncture points and meridians to connective tissue planes,” Anat Rec, 269:257-65, 2002.
11. Kim, Hyunbae, Handbook of Oriental Medicine, Third Edition, Harmony & Balance Press, 2008.
[IMAGE]
Self-managed web sites powered by iEditWeb, Inc.