Massage Therapy and Dupuytren's Disease

Dupuytren's disease and massage therapy

Massage therapy combined with active and passive stretching has been proposed as a potential adjunctive treatment for attenuating Dupuytren's disease (DD) progression and recurrence. Dupuytren's disease is a progressive disorder of the hand that eventually can cause contractures of the affected fingers. The progression of the disease is a complicated process, involving a cascade of molecular and cellular events, in which the cytokine Transforming growth factor beta (TGF-β) plays a fundamental role (Tripoli et al. 2016).

Studies have demonstrated that non-operative treatments such as massage therapy do not cure the condition permanently, but it may affect progression (Larocerie-Salgado et al. 2012 , Christie et al. 2012). These observations support the investigation of massage therapy as an adjunctive treatment strategy for Dupuytren's disease. This post is a brief look at related research, ideally it will serve as a starting point - providing massage therapists and researchers some points of considerations.

The results achieved in our patients demonstrate that in the setting of early onset contracture of the PIPJ [proximal interphalangeal joint] due to DD, a relatively simple splinting regimen, combined with stretching exercises and massage to contracted tissue, can stabilize the progression of contracture and in some cases ameliorate the degree of deformity
— Larocerie-Salgado et al. 2012

Massage Therapy - The Science is Emerging
Based on available evidence the mechanisms by which massage therapy interrupts the sequelae of pathological healing is most likely not in a single unified response, but as a collection of interconnected adaptive responses within the nervous system and soft tissue structures. 

Attenuating Tissue Levels of TGF-β1
As a therapeutic intervention massage therapy has the potential to attenuate TGF-β1 induced fibroblast to myofibroblast transformation. Recent studies have looked at the effect of modeled massage therapy and mechanical stretching on tissue levels of TGF-β1 (Bouffard et al. 2008, Bove et al. 2016). In these studies it was demonstrated that mechanical stretching has the potential to attenuate tissue levels of TGF-β1 and the development of fibrosis.

This is potentially impactful in the treatment of DD because TGF-β1 plays a key role in tissue remodeling and fibrosis (Tripoli et al. 2016).

TGF-β1 plays a role in tissue remodeling, as a therapeutic intervention massage therapy has the potential to attenuate TGF-β1 induced fibroblast to myofibroblast transformation

Davis's law, Attribution:

Attenuating Tissue Levels of TNF-α
Researchers have also described the pathogenic role that tumour necrosis factor (TNF) plays during the course of Dupuytren disease (Verjee et al. 2013, Kalliolias et al. 2016). High levels of TNF contribute to the contractile activity of myofibroblasts, which drives disease development, in Dupuytren's patients.

A study looking at the use of massage for exercise induced muscle damage (Crane et al. 2012) indicates that massage attenuates the production of tumour necrosis factor-α (TNF-α). Attenuating tissue levels of TNF-α with massage may play a role in disease development by reducing the contractile activity of myofibroblasts.

Impacting Inflammation
Persistent inflammation has the potential to interfere with the remodeling of tissue (Rand et al. 2016). There has been modeled experiments to demonstrate the the impact of stretching on inflammation-regulation mechanisms within connective tissue (Berrueta et al. 2016). Another study suggest that the application of massage induces a phenotype change, prompting the transition of M1 macrophages into the M2 macrophages (Waters-Banker et al. 2014).

Neurophysiological Responses
Other research papers have looked at the neurophysiological mechanisms elicited by massage therapy treatments (Bishop et al. 2015, Bialosky et al. 2009Vigotsky et al. 2015). Physiological, psychological, and sociological factors interplay in a complex manner, there are a number of possible ways that massage treatments may trigger neuroimmune responses at both the peripheral and central levels.

Massage therapy as a adjunctive treatment of Dupuytren's disease
Dupuytren's disease is a topic that I follow closely as I have seen second hand the long term effects of this progressive disorder. If these studies are clinically translatable, prophylactic massage treatments may inhibit inflammatory processes and affect the development of fibrosis by mediating differential cytokine production. Consequently this may stabilize the progression of contractures and in some cases ameliorate the degree of deformity. 

Massage therapy is simple to carry out, economical, has very few side effects, the next step for researchers is to look into what sort of dosage and duration would be needed to optimize the effects of this non-invasive approach. As an added note I will emphasize that therapists should be familiar with the condition and cross frictioning need not be vigorous and stretching should be a gentle exploration of ROM.

More to Explore

Duputren's Playlist

  • Dr. David O'Gorman "The extracellular matrix"
  • Drs. Ilse Degreef and Annelien Brauns "RCT Tension versus compression"
  • Dr. Jagdeep Nanchahal "TNF as a therapeutic target"
  • Dr. Jagdeep Nanchahal "Debate: Contracture in Dupuytren is Active"

Research Links
Apostolopoulos, N., Metsios, G.S., Flouris, A.D., Koutedakis, Y., Wyon, M.A. (2015). The relevance of stretch intensity and position-a systematic review. Front Psychol.

Ball, C., Izadi, D., Verjee, L.S., Chan, J., Nanchahal, J. (2016). Systematic review of non-surgical treatments for early dupuytren's disease. BMC Musculoskelet Disord. (OPEN ACCESS)

Baltzer, H., Binhammer, P.A. (2013). Cost-effectiveness in the management of Dupuytren's contracture. A Canadian cost-utility analysis of current and future management strategies. Bone Joint J.

Begovic, H., Zhou, G.Q., Schuster, S., Zheng, Y.P. (2016). The neuromotor effects of transverse friction massage. Man Ther.

Berrueta, L., Muskaj, I., Olenich, S., Butler, T., Badger, G. J., Colas, R. A., . . . Langevin, H. M. (2016). Stretching Impacts Inflammation Resolution in Connective Tissue. Journal of Cellular Physiology.

Best, T., Gharaibeh, B., & Huard, J. (2013). Stem cells, angiogenesis and muscle healing: A potential role in massage therapies? British Journal of Sports Medicine.

Bialosky, J.E., Bishop, M.D., Price, D.D., Robinson, M.E., George, S.Z. (2009). The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. Man Ther.

Bishop, M. D., Torres-Cueco, R., Gay, C. W., Lluch-Girbés, E., Beneciuk, J. M., & Bialosky, J. E. (2015). What effect can manual therapy have on a patient's pain experience? Pain Management.

Blazevich, A.J., Cannavan, D., Waugh, C.M., Miller, S.C., Thorlund, J.B., Aagaard, P., Kay, A.D. (2014). Range of motion, neuromechanical, and architectural adaptations to plantar flexor stretch training in humans. J Appl Physiol (1985).

Bochaton-Piallat, M., Gabbiani, G., & Hinz, B. (2016). The myofibroblast in wound healing and fibrosis: Answered and unanswered questions. F1000Research. (OPEN ACCESS)

Bouffard, N.A., Cutroneo, K.R., Badger, G.J., White, S.L., Buttolph, T.R., Ehrlich, H.P., Stevens-Tuttle, D., Langevin, H.M. (2008). Tissue stretch decreases soluble TGF-beta1 and type-1 procollagen in mouse subcutaneous connective tissue: evidence from ex vivo and in vivo models. J Cell Physiol. (OPEN ACCESS)

Bove, G., Harris, M., Zhao, H., & Barbe, M. (2016). Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury. Journal of the Neurological Sciences.

Brauns, A., Van Nuffel, M., De Smet, L., Degreef, I. (2017). A clinical trial of tension and compression orthoses for Dupuytren contractures. J Hand Ther.

Cezar, C.A., Roche, E.T., Vandenburgh, H.H., Duda, G.N., Walsh, C.J., Mooney, D.J. (2016). Biologic-free mechanically induced muscle regeneration. Proc Natl Acad Sci U S A. (OPEN ACCESS)

Chaitow, L. (2016). Dosage and manual therapies – Can we translate science into practice? Journal of Bodywork and Movement Therapies.

Chaitow, L. (2016). New evidence of a dynamic fascial maintenance and self-repair process. Journal of Bodywork and Movement Therapies.

Chaitow, L., (2017.) Telocytes: connective tissue repair and communication cells. Journal of Bodywork and Movement Therapies.

Chapelle, S. (2017). Understanding and approach to treatment of scars and adhesions.

Chapman, M.A., Meza, R., Lieber, R.L. (2016). Skeletal muscle fibroblasts in health and disease. Differentiation.

Christie, W.S., Puhl, A.A., Lucaciu, O.C. (2012). Cross-frictional therapy and stretching for the treatment of palmar adhesions due to Dupuytren's contracture: a prospective case study. Man Ther.

Crane, J., Ogborn, D., Cupido, C., Melov, S., Hubbard, A., Bourgeois, J., & Tarnopolsky, M. (2012). Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced Muscle Damage. Science Translational Medicine.

Cuerrier, C., Pelling, A. (2015). Cells, Forces, and the Microenvironment. Pan Stanford Publishing. Chapter 5: The Mechanical Regulation of Myofibroblasts Mechanically Guided Matrix Remodeling and Prevention of Fibrosis in Regenerative Medicine; Jenna L. Balestrini and Boris Hinz

Dunn, S. L., & Olmedo, M. L. (2016). Mechanotransduction: Relevance to Physical Therapist Practice--Understanding Our Ability to Affect Genetic Expression Through Mechanical Forces. Physical Therapy.

Guimberteau, J., Delage, J., & Wong, J. (2010). The role and mechanical behavior of the connective tissue in tendon sliding. Chirurgie De La Main.

Hicks, M., Cao, T., Campbell, D., & Standley, P. (2012). Mechanical strain applied to human fibroblasts differentially regulates skeletal myoblast differentiation. Journal of Applied Physiology.

Hinz, B. (2007). Formation and function of the myofibroblast during tissue repair. J Invest Dermatol. (OPEN ACCESS)

Hofer, H.R., Tuan, R.S. (2016). Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther. (OPEN ACCESS)

Kai, F., Laklai, H., & Weaver, V. M. (2016). Force Matters: Biomechanical Regulation of Cell Invasion and Migration in Disease. Trends in Cell Biology.

Kalliolias, G.D., Ivashkiv, L.B. (2016). TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. (OPEN ACCESS)

Karkampouna, S., Kreulen, M., Obdeijn, M.C., Kloen, P., ... Kruithof-de Julio, M. (2016). Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren's Disease). Curr Mol Biol Rep. (OPEN ACCESS)

Kay, A.D., Husbands-Beasley, J., Blazevich, A.J. (2015). Effects of Contract-Relax, Static Stretching, and Isometric Contractions on Muscle-Tendon Mechanics. Med Sci Sports Exerc. 

Kay, A.D., Richmond, D., Talbot, C., Mina, M., Baross, A.W., Blazevich, A.J. (2016). Stretching of Active Muscle Elicits Chronic Changes in Multiple Strain Risk Factors. Med Sci Sports Exerc.

Kwan, P.O., Tredget, E.E. (2017). Biological Principles of Scar and Contracture. Hand Clin.

Larocerie-Salgado, J., Davidson, J. (2012). Nonoperative treatment of PIPJ flexion contractures associated with Dupuytren's disease. J Hand Surg Eur.

Laumonier, T., & Menetrey, J. (2016). Muscle injuries and strategies for improving their repair. Journal of Experimental Orthopaedics. (OPEN ACCESS)

Liu, W., O'Gorman, D.B., Gan, B.S. (2013). Operative trends and physician treatment costs associated with Dupuytren's disease in Canada. Can J Plast Surg.  (OPEN ACCESS)

Nanchahal, J., Hinz, B. (2016). Strategies to overcome the hurdles to treat fibrosis, a major unmet clinical need. Proc Natl Acad Sci U S A. (OPEN ACCESS)

Parravicini, G., Bergna, A., (2017). Biological effects of direct and indirect manipulation of the fascial system. Narrative review, Journal of Bodywork & Movement Therapies.

Pelletier, R., Higgins, J., Bourbonnais, D. (2017). The relationship of corticospinal excitability with pain, motor performance and disability in subjects with chronic wrist/hand pain. J Electromyogr Kinesiol.

Rand, E., Gellhorn, A.C. (2016). The Healing Cascade: Facilitating and Optimizing the System. Phys Med Rehabil Clin N Am.

Rapaport, M.H., Schettler, P., Bresee, C. (2012). A preliminary study of the effects of repeated massage on hypothalamic-pituitary-adrenal and immune function in healthy individuals: a study of mechanisms of action and dosage. J Altern Complement Med. (OPEN ACCESS)

Rayan, G.M., Moore, J. (2005). Non-Dupuytren's disease of the palmar fascia. J Hand Surg Br.

Schleip, R. (2016) Mechanotransduktion: von der zellulären Ebene bis zum ganzen Körper (Mechanotransduction: from the cellular level to the entire body). Osteopathische Medizin. [Article in German]

Sefton, J.M., Yarar, C., Berry, J.W., Pascoe, D.D. (2010). Therapeutic massage of the neck and shoulders produces changes in peripheral blood flow when assessed with dynamic infrared thermography. J Altern Complement Med.

Stecco, A., Stern, R., Fantoni, I., Caro, R., & Stecco, C. (2016). Fascial Disorders: Implications for Treatment. Pm&r.

Thompson, W. R., Scott, A., Loghmani, M. T., Ward, S. R., & Warden, S. J. (2016). Understanding Mechanobiology: Physical Therapists as a Force in Mechanotherapy and Musculoskeletal Regenerative Rehabilitation. Physical Therapy. (Open Access)

Tripoli, M., Cordova, A., Moschella, F. (2016). Update on the role of molecular factors and fibroblasts in the pathogenesis of Dupuytren's disease. J Cell Commun Signal. (OPEN ACCESS)

Verhoekx, J.S., Mudera, V., Walbeehm, E.T., Hovius, S.E. (2013). Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease. Plast Reconstr Surg.

Verjee, L. S., Verhoekx, J. S., Chan, J. K., Krausgruber, T., Nicolaidou, V., Izadi, D., . . . Nanchahal, J. (2013). Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target. Proceedings of the National Academy of Sciences. (OPEN ACCESS)

Viganò, M., Sansone, V., d'Agostino, M.C., Romeo, P., Perucca Orfei, C., de Girolamo, L. (2016). Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders. J Orthop Surg Res. (OPEN ACCESS)

Vigotsky, A. D., & Bruhns, R. P. (2015). The Role of Descending Modulation in Manual Therapy and Its Analgesic Implications: A Narrative Review. Pain Research and Treatment.  (OPEN ACCESS)

Wallwork, S.B., Bellan, V., Catley, M.J., Moseley, G.L. (2016). Neural representations and the cortical body matrix: implications for sports medicine and future directions. Br J Sports Med.

Waters-Banker, C., Dupont-Versteegden, E. E., Kitzman, P. H., & Butterfield, T. A. (2014). Investigating the Mechanisms of Massage Efficacy: The Role of Mechanical Immunomodulation. Journal of Athletic Training. (OPEN ACCESS)

Weppler, C.H., Magnusson, S.P. (2010). Increasing muscle extensibility: a matter of increasing length or modifying sensation? Phys Ther.

Zein-Hammoud, M., & Standley, P. R. (2015). Modeled Osteopathic Manipulative Treatments: A Review of Their in Vitro Effects on Fibroblast Tissue Preparations. JAOA.

Zhao, B., Guan, H., Liu, J.Q., Zheng, Z., Zhou, Q., Zhang, J., Su, L.L., Hu, D.H. (2017). Hypoxia drives the transition of human dermal fibroblasts to a myofibroblast-like phenotype via the TGF-β1/Smad3 pathway. Int J Mol Med.

Zhou, C., Liu, F., Gallo, P.H., Baratz, M.E., Kathju, S., Satish, L. (2016). Anti-fibrotic action of pirfenidone in Dupuytren's disease-derived fibroblasts. BMC Musculoskelet Disord. (OPEN ACCESS)