By Ross Turchaninov, M.D., Ph.D.
Originally published in Massage & Bodywork magazine, October/November 2000.
The present time opens exciting perspectives for American massage and bodywork practitioners. Thanks to a new philosophy, the medical values of massage are getting more and more recognition from clients/patients, as well as from other health and medical practitioners. I am sure that this inevitable process will finally restore massage therapy within the arsenal of modern American medicine. Massage practitioners are playing a major role in this process. It is their job to help the clients and convince other health practitioners of the benefits of massage therapy. This latter task is especially difficult because the general opinion of doctors, chiropractors and physical therapists regarding the medical benefits of massage therapy remains skeptical. Noting this, it would be extremely helpful to equip massage practitioners with the latest information about scientific discoveries that help us to understand mechanisms of the therapeutic impacts of massage therapy on the body, organ, tissue and cellular levels.
Pressure’s Therapeutic Impact
Massage therapy has a limited arsenal of therapeutic remedies. The massage practitioner can count only on different forms of pressure (including vibration), stretching, and the activation of temperature receptors. Between these three modalities, pressure is the main therapeutic tool, with stretching and temperature receptors’ activation playing a supportive role in the treatment. Thus, discussion of mechanisms of the therapeutic effect of massage treatment will refer us mostly to the mechanisms of pressure’s therapeutic impact.
Pressure is a physical force which is used by massage practitioners to achieve therapeutic results. Thus, the therapist converts the kinetic energy of massage strokes into various physiological phenomenons on tissue and cellular levels of the body (e.g. changes of interstitial pressure), as well as into a chain of electrochemical reactions in the massaged area and the whole organism.
The final success of therapeutic or medical massage treatment directly depends on the correct application of this pressure. That includes the right combination of proper techniques; the form of application (i.e. permanent or intermittent); speed of application; intensity of application (i.e. light-moderate-deep pressure); and the area of application. Only after careful evaluation of all these parameters and formulation of the right protocol of treatment can a massage practitioner expect stable results from the therapy. If the chosen schema does not work, adjustments to the protocol have to be made. Sometimes these adjustments can completely change the initial schema of treatment. Remember one important rule: If treatment is unsuccessful, of course in cases when massage is indicated, it means that the practitioner developed the wrong protocol of treatment.
Indirect Reflex Mechanism of Massage Therapy
Massage has two mechanisms of therapeutic impact: reflex (indirect) effect and local (direct) effect. This classification is very approximate because for example the local mechanism is a component of the reflex mechanism. However it makes representation of the material easier. Reflex therapeutic impact of massage therapy has a complex mechanism. This is an important subject for another discussion. However, I want to emphasize one important point. The basic concept of reflex mechanism of massage therapy is the formation of reflex zones. Reflex zones are areas of soft tissue abnormalities which are secondarily formed as a reflex response to the various visceral and somatic disorders. In the cases of visceral (i.e. inner organ) disorders, the reflex zones are formed only after three months of medical history of these pathologies. In the cases of somatic pathologies this period is shorter but still takes at least two to three weeks. Thus, in the every new case of somatic disorders, the local therapeutic effect of massage treatment is the leading mechanism. Therefore, I will concentrate on the local mechanism of massage therapy. I refer those who are interested in knowing more about the reflex mechanism of massage therapy to Massage & Bodywork, June/July 1999 or to the Medical Massage textbook, Vol. 1.
Direct Local Mechanism of Massage Therapy
Everyone who practices massage as a treatment procedure experiences cases when two to three sessions eliminate the patient’s somatic problem with complete restoration of all affected functions. I don’t mean just pain relief, I am talking about actual stimulation of the healing process to obtain stable therapeutic results. Examples can be found in cases of epycondylitis, tendinitis, muscular and ligamental injuries and so on. What mechanisms are responsible for such a “miraculous” effect? The local effects which traditionally explain the therapeutic impact of massage treatment are pain relief, peripheral arterial vasodilation, increasing of venous and lymph drainage, and stimulation of local metabolism. However, practically all experts agree that these positive changes have transitory character and slowly faded within 2-3 hours after the end of a session. Thus, to obtain stable therapeutic results, the massage practitioner has to perform a course of treatment. If we accept this point of view as ultimately correct, we cannot fit cases with rapid stimulation of the healing process into this concept or we should not take them into consideration. However, they do exist and do demand explanation. As you will see below, more powerful mechanisms than we once thought play a major role in the healing potential of massage therapy on the local level.
The Effect of Mechanical Stimuli on the Cellular Metabolism Role of Cytoskeleton
The therapeutic potential of different types of massage has started to slowly attract the attention of scientists in the various fields of medicine. In previous years, scientists drew their conclusions mostly from clinical experiments and observations. However, modern technical devices with high resolution capacity allowed scientists to obtain important information from the purely experimental models as well. These findings revealed mechanisms of physiological and therapeutic impacts of mechanical pressure on the cellular and subcellular level. To fully represent this information, I think it will be helpful to take a short trip into cellular biology and biochemistry.
Every cell contains a cellular membrane and cytoskeleton, cytoplasm with organelles, and nucleus with nucleous. Figure 1 presents the general view of the cell. The structure and functions of all cellular components are well known and it is not the subject of our discussion. However, latest findings about the cytoskeleton and its relation to external mechanical stimuli applied to the cell are breakthroughs in the understanding of the therapeutic effect of mechanostimulation on living cells and tissues.
The cytoskeleton is a complex system of fibrillar structures in the cytoplasm. It can be compared to the human skeleton which provides a frame for our body and its dynamic support. There are three types of fibrils in the cytoplasm which form the cytoskeleton:
• Microtubules — Microtubules have a diameter of approximately 25 nm and build up from protein tubulin. During mitosis, microtubules form the spindle which pulls chromosomes into newly-formed cells.
• Actin filaments — These have a diameter of approximately 10 nm and consist of proteins: actin, myosin and energy source APT. They are a major contractile apparatus of the cell.
• Intermediate filaments — These fibrils have a diameter of 7 nm and form a net throughout all the cytoplasm with especially high density around the nucleus. This net is not flat, but is instead a three-dimensional structure through the entire thickness of cytoplasm. It links cellular organelles, the nucleus and cytoplasmic membrane together to form the cell.
Jain, M.K., et al. (1990) in an experimental study on human fibroblasts showed that microfibrils of the cytoskeleton have a special arrangement responsible for an increase in intercellular stress in the direction of applied pressure and an actual decrease of intercellular stress in the direction which is perpendicular to the applied pressure. Thus, the cytoskeleton is able to transfer the mechanical energy of external stimuli into the cell or annihilate these stimuli.
Opposite to the human skeleton, the cytoskeleton is an extremely dynamic structure. It is in a state of permanent change. In fact, the cell is able to completely dissolve and resynthesize the cytoskeleton in several minutes. Fibroblasts are major repair cells of the human body, because they produce the direct precursor of collagen, known as procollagen. The collagen itself is a most abundant protein which forms the structural frame of all organs and tissues.
From the time of its discovery at the beginning of the century, the cytoskeleton was always viewed as a purely mechanical structure that provides the shape of the cell and participates in cell motility and migration (e.g. leukocytes, natural killer cells, etc.). The cytoskeleton was also viewed as one of the key mechanical components of cell division. However, modern experimental equipment allowed scientists to set up and conduct more detailed studies of the structure and functions of the cytoskeleton. Thanks to these studies, we now know the following functions of the cytoskeleton:
1. Providing the cellular morphology; (i.e. shape of the cell).
2. Distribution of the cellular organelles.
3. Intercellular movements of cytoplasm and organelles.
4. Participation in cellular division.
5. Motility of the cell.
6. Control over the cytoplasmic membrane.
7. Connection of the cytoplasmic membrane to the nucleoskeleton and stabilization of the nucleus.
8. The regulation of protein production.
9. Control over genes’ expression.
Functions 1-5 were always associated with the cytoskeleton. However, for our discussion, Functions 6-9 are extremely important, and their discovery is one of the greatest achievements of modern cellular biology. Of course, we are interested in theoretical conclusions that can be projected onto massage therapy and clarify its healing mechanisms. Let’s see how the cytoskeleton and, consequently, cellular functions are affected by the external mechanical stimuli.
Control Over Cytoplasmic Membrane
A cytoplasmic membrane surrounds the cells and actively interacts with the environment (i.e. extracellular matrix). It has a thickness of 7.5 nm or 1/4,000 of an inch, and is made up of double layers of phospholipids with integrated proteins. Figure 3 shows the structure of the cytoplasmic membrane. The integrated proteins work as gates which connect the external environment and inner part of the cell. Any macromolecules the cell needs for its metabolism pass into the cell through these gates. They also allow the new synthesized proteins or waste to be secreted from the cell. Cytoplasmic proteins have approximately 50 percent of the membrane’s mass and form the net of receptors over the entire outer surface of the cytoplasmic membrane. Thus, any outside molecule has to first interact with these receptors to be recognized. Only after this occurs will the gate open and let it in.
Any mechanical stimuli (e.g. changes in the interstitial pressure) affect the receptors on the cytoplasmic membrane. After exposure to the original stimuli, receptors are able to convert mechanical energy into chemical stimuli that can be conducted inside of the cell. Jain, M.K., et al. (1990) concluded that mechanical signals can be converted into chemical signals in the form of cyclic-AMP. Komuro, I., et al. (1991) also pointed out the activation and participation in this process of one of the key enzymes of cellular metabolism, protein kinasa C. Not all receptors in the cytoplasmic membrane act as mechanoreceptors. More likely, that one particular family of proteins, called integrins, reacts to the mechanical stimulation (Wang, et al., 1993).
The fibrils of the cytoskeleton are deeply anchored in the membrane, including the protein receptors. The cytoskeleton has major regulatory control over the function, arrangement and even amount of protein receptors incorporated into the membrane. Thus, by regulation of cytoplasmic proteins, the cytoskeleton changes the metabolism of the whole cell by controlling the amount and intensity of impulses conducted from the extracellular matrix into the cell (Jain, et al., 1990).
Gataullin, R.R. and Zaripov, A.T. (1988) examined the effect of colchicine on the mechanoreceptive ability of single Pacinian corpuscles which were isolated from the mesentery of a cat. Pacinian corpuscles are receptors which are activated by vibratory stimuli. Thus, any form of external vibratory stimuli activate Pacinian corpuscles which form the afferent sensory flow of nervous signals (i.e. action potentials) to the central nervous system. As a result, the perception of vibration is formed.
The colchicine is known to selectively disrupt the intracellular microtubules of the cytoskeleton without any additional damage to the living cell. After the exposure of the Pacinian corpuscles to the colchicine, the complete depression of the mechanoreceptor’s ability to generate action potentials was detected. The results of this study leave no doubt about the controlling function of the cytoskeleton over the cytoplasmic membrane. The authors tested the single mechanoreceptor cell which normally produces the action potentials after the direct deformation of its cytoplasmic membrane by vibration stimuli. The colchicine disrupted the fibrils of the cytoskeleton and, consequently, the Pacinian corpuscle lost its ability to generate action potentials because of interruption of conductance from the cytoplasmic membrane’s receptors into the cell.
Connection of the Cytoplasmic Membrane to the Nucleoskeleton
The nucleus stores the vital information of all living objects — DNA. The nucleus is surrounded by its own nuclear membrane which has pores that open into the cytoplasm and endoplasmic reticulum. Through these pores, the permanent interchange of different molecules between the cytoplasm and the nucleus occurs. The nucleus also has its own nucleoskeleton. Some authors consider the cytoskeleton and nucleoskeleton as the same, continuous structure because of their striking similarity (McKeon, F.D. et al., 1986). However, even if this hypothesis is wrong, the cytoskeleton still has very high density all around the nucleus, and is also able to control the activity of the pores in the nuclear membrane.
One of the most important functions of the cytoskeleton is its ability to conduct information from the receptors of the cytoplasmic membrane directly to the nucleus, with the following changes in cell proliferation, protein synthesis and genes expression. Every mechanical stimulus which is applied to the living cell affects the mechanoreceptors first. Their activation immediately causes the reorientation of cytoskeletal fibrils with subsequent nucleus distortion (Maniotis, J. et al., 1977).
Wang, N., et al. (1993) see cytoplasmic receptors, cytoskeleton fibrils and the nucleus as one “hard-wired” structure, where mechanical stimulation of the receptor’s site immediately produces deep morphological and biomechanical changes in the whole cell, including the nucleus.
Regulation of Protein Production of Genes Expression
After we clarified the relationship between the external mechanical stimuli receptors, cytoplasmic membrane, cytoskeleton and nucleus, we have to look at how this chain of events affects the cell functions (i.e. proliferation, protein synthesis and genes expression). One more time, let’s start from the beginning with the example of the human fibroblast.
The external mechanical stimuli activates the receptors in the cytoplasmic membrane of the fibroblast. These mechanical stimuli are converted into chemical signals and cause the reorientation of the cytoskeleton in the direction of the applied force. The cytoskeleton reorientation causes nucleus distortion, and it responds with increased DNA synthesis and replication (Curtis and Seehar, 1978; Sornjen et al., 1980; Brunett, 1984), increasing the synthesis of messenger-RNA (m-RNA) — i.e. transcription of information from the replicated DNA (Komuro et al., 1991). The newly synthesized chain of m-RNA, which carries identical information about the structure of the replicated DNA, leaves the nucleus through the pores in the nuclear membrane directly into rough endoplasmic reticulum. Here, m-RNA associates with ribosomes and starts the process of translation — i.e. protein synthesis. This process is also supported by transport-RNA (t-RNA), which pulls the required amino acids from the cytoplasm to the m-RNA-ribosomal complex and attaches them to the newly synthesized molecule of procollagen. This transport of amino acids by t-RNA is also under control of the cytoskeleton (Bereiter-Hahn et al., 1987). Procollagen is a direct precursor of collagen. Procollagen needs to be secreted from the fibroblast into extracellular matrix, where its conversion into a newly formed molecule of collagen occurs. Thus, mechanical stimuli activate the fibroblasts and stimulate procollagen synthesis which leads to the increasing of collagen and extracellular matrix production at the injured site. Collagen is the most abundant protein of any life organism and it comprises approximately one-third of all proteins in the body (Geneser, 1986). The role of collagen is critical for every living organism because it forms the actual frame of all tissues and inner organs.
What practical outcomes are caused by all these changes on the cellular level, and how can they explain the therapeutic impact of massage therapy?
Leung, D.Y.M. et al. (1976) reported that smooth muscle cells significantly increased production of collagen after the application of mechanical stimuli. However, their proliferation was not detected.
Curtis, A.S.G. and Seehar, G.M. (1978) showed that mechanical stress stimulates the DNA synthesis and division of fibroblasts from chick embryos. The authors detected the increase in the mitotic index in the experimental study up to 5.1 ± 1.5, vs. the same parameter in a control study, 2.3 ± 0.7. The mitotic index reflects the mitotic frequency and proportion of cells in the phase of cellular division. Thus, mechanical signals are able to augment the cells’ proliferation (especially fibroblasts), which is very important for the stimulation of the healing process at the site of an injury.
Shirinsky, V.P. et al. (1989) showed that the mechanical deformation of human endothelial cells in vitro produces their rapid growth and elongation (within three hours), with the formation of a multilayered structure from the monolayer culture. Within 48 hours, endothelial cells became uniformly oriented along the axis of the future vessel. Endothelial cells form the walls of arterial, venous and lymphatic vessels. Thus, mechanical energy is able to stimulate the new capillaries’ formation.
Jain, M.K. et al. (1990) showed that direct mechanical influence on human fibroblasts causes cellular growth to increase 1.7 times, increasing protein synthesis up to 48 percent, and increasing intercellular cyclic adenosine monophosphate (cAMP) 3.7 times in 24 hours after the mechanical stimulation. The fibroblast activation, with a subsequent increase in collagen production, is a major process of healing which affects practically every tissue in the human body.
Wirtz, H.R.W. and Dobbs, L.G. (1990) reported that after a single application of mechanical stimuli to the alveolar type II cells, they were able to increase Ca +2 exocytosis and surfactant secretion during the next 15-30 minutes. The surfactant is a special fluid that covers the inner surface of alveoli and prevents their collapse during expiration. Thus, the authors showed that the functions of the inner organs’ cells also can be affected by mechanical stimulation.
Komuro, I. et al. (1991) found in an experimental study on rats’ neonatal cardiocytes that mechanical stress stimulates the cardiac cells’ hypertrophy and specific genes’ expression. The authors showed that total RNA content in the experimental group increased up to 45 percent, vs. no increase in the control group during 24 hours. The genes’ expression is one of the most intimate processes of nature. The ability of mechanical stimuli to affect the genes’ expression brings a new understanding of the mechanisms that are responsible for many visceral disorders.
Chen, B. M. and Grinnel, A.D. (1995) found that stretching the skeletal muscle of a frog in the physiological range (up to 2 mm) more than doubled the spontaneous and evoked release of the neurotransmitter acethylcholine from its motor nerve terminal, with an accompanying increasing of frequency of end-plate potentials. The mechanism of this effect is the activation of integrins in the cytoplasmic membrane, and additional mobilization of Ca +2 from internal and external sources. These data allow us to conclude that light stretching of the skeletal muscles at the end of massage treatment will stimulate the muscle tone and muscular performance.
Davidson, C.G. et al. (1997) examined the effect of soft tissue mobilization (intense cross-friction) on experimental tendinitis caused by the injection of enzyme collagenase into the Achilles tendon of 20 rats. The results obtained from experimental and control groups were examined with light microscopy, electron microscopy, immunoelectron microscopy and by gait analysis. The authors found that the mean increase of the fibroblast count in an experimental group was 15 ± 11, vs. 3 ± 3 in the control group. All fibroblasts in the experimental group exhibited a highly developed rough endoplasmic reticulum, which is clear evidence of the stimulation of collagen production. Thus, the mechanical stimuli, cross-friction in this case, attract the fibroblasts from the neighboring areas to the site of treatment, with an accompanying stimulation of collagen production and healing of affected tendons.
Gehlsen, G.M. et al. (1999) also examined the effect of soft tissue mobilization with different amounts of applied pressure on the fibroblasts. The authors used the same experimental model of tendinitis in the Achilles tendon. They found that the application of strong pressure stimulated the healing process in the tendon much faster (fibroblast count = 375) compared to the treatment with light (fibroblast count = 190) or moderate (fibroblast count = 250) pressure. For the first time in modern literature, the authors also established a clear connection between mechanical stimuli, their therapeutic effect on somatic pathology in the form of soft tissue mobilization, and their effect on cellular functions.
To really understand the significance of all this information, the reader should realize that some of the reported effects were obtained from cells placed in the experimental conditions outside of the body (i.e. in vitro). Thus, stimulation of cellular activity was a result of purely mechanical stimulation of these cells without the participation of any other systems traditionally responsible for the coordination of cellular activity: nervous, endocrine or immune.
At the end of this short review, I want to quote the conclusion from an article by A.J. Maniotis, C. S. Chen and D.E. Ingber published in Proc. of the National Academy of Sciences of the USA in 1997: “... direct mechanical linkages throughout living cells raise the possibility that regulatory information, in the form of mechanical stress or vibration, may be rapidly transferred from these cell surface receptors to distinct structures in the cell and nucleus, including ion channels, nuclear pores, nucleoli, chromosomes, and perhaps even individual genes, independent of ongoing chemical signaling mechanisms.”
Thus, the latest scientific discoveries of cellular biologists and biochemists do not leave any doubts about the stimulating impact of mechanical stimuli on the cellular functions. Mechanical stimuli in the form of massage or any other type of soft tissue mobilization repetitively applied to the place of injury are able to increase collagen production by the stimulation of fibroblasts’ functions and by attracting new cells from neighboring areas. However, increased collagen production alone is not enough to heal the injured site. The correct orientation of collagen fibers is an equally important element. Without the proper orientation of collagen fibers, an increase in collagen production is useless. Are mechanical stimuli somehow able to affect this process as well? We should answer this question positively. Numerous scientific reports support this conclusion. The piezoelectric phenomenon in the soft tissues is a unique electrophysiological mechanism responsible for the correct orientation of collagen fibers. We will discuss this equally exciting topic in the next issue of Massage & Bodywork.
To find out more about the medical benefits of massage therapy and various techniques of medical massage treatment, visit www.aesculapbooks.com. You can find comprehensive educational information on every subject regarding the theoretical foundation and practical application of medical and therapeutic massage in Medical Massage, Vol. I and Therapeutic Massage: A Scientific Approach 1. To order, call 602/404-1583, or purchase on-line at www.aesculapbooks.com.
Ross Turchaninov, M.D., author of the Medical Massage textbook, graduated in 1983 from the Odessa Medical School in the Ukraine and was selected to the Kiev Orthopedic Institute for Scientific Research where he specialized in trauma surgery and post-traumatic rehabilitation. From 1985-88, the author worked as chief supervisor of the rehabilitation program of the Ministry of Public Health of the Ukraine. In 1990, he graduated from the chiropractic and medical massage program designed for medical doctors at the Kiev Institute and worked as a senior scientific researcher there. He is the author of 20 scientific articles and two patents in the Ukraine. In 1992, Turchaninov moved to the United States.
- Bereiter-Hahn, J., Anderson, O.R., Rief, W.E.: Cytomechanics. “Springer-Verlag,” Berlin, 1987.
- Brunett, D.M.: Mechanical Stretching Increases the Number of Epithelial Cell Synthesizing DNA in Culture. J Cell Sci., 69: 34-35, 1984.
- Chen, B-M., Grinnell, A.D.: Integrins and Modulation of Transmitter Release from Motor Nerve Terminals by Stretch; Science, 269: 1578-1580, 1995.
- Curtis, A.S.G., Sheehar, G.M.: The Control of Cell Division by Tension or Diffusion; Nature, 274: 52-53, 1978.
- Davidson, C.J., Ganion, L.R., GehIsen, G.M., Verhoestra, B., Roepke, J.E., Sevier, T.I.: Rat Tendon Morphologic and Functional Changes Resulting from Soft Tissue Mobilization. Med Sci. Sports Exer., 29: 313-319, 1997.
- Gataulin, R.R., Zripov, A.T.: “The Role of Cytoskeleton in Mechanoreceptor Activity of Pacinian Corpuscles,” Mechanoreceptors: Development, Structure and Function: 209-211. Edited by E.P. Hnik, T. Soukup, R. Vejsada, J. Zelena. “Premium Press,” New York, 1988.
- Gehlsen, G.M., Ganion, L.R., Helllfst, R.: Fibroblast Responses to Variation in Soft Tissue Mobilization Pressure. Med. Sci. Sports Med., 31(4): 531-535, 1999.
- Geneser, F.: Textbook QJ’Histology. “Munksgaard Lea & Febiger,” Philadelphia, 1986.
- Jain, M.K., Berg, R-A., Tandon, G.P.: Mechanical Stress and Cellular Metabolism in Living Soft Tissue Composites. Biomaterials, It: 465-471, 1990.
- Komuro, I., Katoh, Y., Kaida, T., Shibazaki, Y., Kurabayashi, M., Hoh, E., Takaku, F., Yazaki, Y.: Mechanical Loading Stimulates Cell Hypertrophy and Specific Gene Expression in Cultured Rat Cardiac Myocytes. J Biol. Chem., 266(2): 1265-1268, 199 1.
- Leung, D.Y.M., Gladov, S., Mathews, M.B.: Cyclic Stretching Stimulates Synthesis of Martix Components by Arterial Smooth Muscle in Vitro. Science, 191: 475-477, 1976.
- Maniotis, A.J., Chen, C.s., Ingber, D.E.: Demonstration of Mechanical Connections Between Integrins, Cytoskeletal Filaments, and Nucleoplasm that Stabilize Nuclear Structure. Proc. Nat. Acad Sci. USA, 94(3): 849-854, 1997.
- McKeon, F.D., Krischner, M.W., Caput, D.: Homologies in Both Primary and Secondary Structure Between Nuclear Envelope and Intermediate Filament Proteins. Nature, 319: 463-468, 1986.
- Shirinsky, V.P., Antonov, A.S., Birukov, K.G., Sobolevsky, A.V., Romanov, Y.A., Kabaeva, N.V., Antonova, G.N., Smirnov, V.N.: Mechano-Chemical Control of Human Endothelium Orientation and Size. J. Cell Biol., 109, 331-339, 1989.
- Sorn en, D., Binderman, I., Berger, E., Harell, A.: Bone Remodeling Induced by Physical Stress in Protoglandin E2 Mediated. Biochim. Biophys. Acta., 627: 91-100, 1980.
- Wang, N., Butler, J.P., Ingber, D.E.: Mechanotransduction Across the Cell Surface and Through the Cytoskeleton. Science, 260: 1124-1127, 1993.
- Wirtz, H.R.W., Dobbs, L.G.: Calcium Mobilization and Exocytosis after One Mechanical Stretch of Lung Epithelial Cells. Science, 250: 1266-1273, 1990.