Molecular and cellular mechanisms of radial shock wave therapy Dr. Christoph Schmitz, MD Full Professor and Head Department of Neuroanatomy, Ludwig-Maximilians-University Munich, Germany Adjunct Professor Department of Neuroscience, Mount Sinai School of Medicine New York, NY, USA Medical Scientific Officer EMS Electro Medical Systems Nyon, Switzerland

Example: calcifying tendinitis of the shoulder Vavken et al. (2009)

Don‘t compare apples with pies...

Compare within the same settings... Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Enthusiastic patients – successful practice! A treatment modality becomes successful when... we know how it works we know that it works we know why it works your patients become enthusiastic about it! Enthusiastic patients – successful practice! Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

A happy patient...

A patient... (at Home Depot Stadium, Los Angeles, CA, USA on July 19, 2009)

A happy patient...

RSWT® at AC Milan (www.acmilan.com/InfoPage.aspx?id=41293) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

RSWT® at AC Milan (www.acmilan.com/InfoPage.aspx?id=41293) Objectives: to optimising the team‘s results to enable athletes to achieve the most optimum performance possible, to reduce the risk of injury, and […] Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Milanello Training Center, Carvado, Italy, on April 26, 2011

What are shock waves? Wikipedia: A shock wave (also called shock front or simply "shock") is a type of propagating disturbance. Like an ordinary wave, it carries energy and can propagate through a medium (solid, liquid or gas) [...]. Shock waves are characterized by an abrupt, nearly discontinuous change in the characteristics of the medium. Across a shock there is always an extremely rapid rise in pressure, temperature and density of the flow. [...] A shock wave travels through most media at a higher speed than an ordinary wave.

What are shock waves? Encyclopedia Britannica online: a „[...] strong pressure wave in any elastic medium such as air, water, or a solid substance, produced by supersonic aircraft, explosions, lightning, or other phenomena that create violent changes in pressure. Shock waves differ from sound waves in that the wave front, in which compression takes place, is a region of sudden and violent change in stress, density, and temperature. Because of this, shock waves propagate in a manner different from that of ordinary acoustic waves. In particular, shock waves travel faster than sound, and their speed increases as the amplitude is raised; but the intensity of a shock wave also decreases faster than does that of a sound wave, because some of the energy of the shock wave is expended to heat the medium in which it travels."

What are therapeutic shock waves? – Ogden et al. (2001) Characteristics of therapeutic shock waves (1) (Source: Ogden JA, Tóth-Kischkat A, Schultheiss R: Principles of Shock Wave Therapy. Clin Orthop Relat Res 2001 [387] 8-17) Typical form of a therapeutic shock wave

What are therapeutic shock waves? Ogden et al., Clin Orthop Rel Res 2001;(387):8-17: “A shock wave is a sonic pulse that has certain physical characteristics. There is a high peak pressure, sometimes more than 100 MPa (500 bar), but more often approximately 50 to 80 MPa, a fast initial rise in pressure during a period of less than 10 ns, a low tensile amplitude (up to 10 MPa), a short life cycle of approximately 10 µs, and a broad frequency spectrum, typically in the range of 16 Hz to 20 MHz.” Shrivastava and Kailash, J Biosci 2005;30:269-275: “Shock waves are characterized by high positive pressure, a rise time lower than 10 ns and a tensile wave.”

Generation of therapeutic shock waves Four principles to generate therapeutic shock waves electro- hydraulic piezo-electric electro- magnetic pneumatic Ossatron Orbason Orthospec Epos Ultra Sonocur Swiss Dolorclast D-ACTOR

Generation of therapeutic shock waves Mode of operation of radial shock wave devices (Swiss Dolorclast) Schematic representation of the mode of operation of the handpiece of the Swiss Dolorclast. Compressed air is used to fire a projectile within a guiding tube that strikes a metal applicator placed on the skin. The projectile generates stress waves in the applicator that transmit pressure waves into tissue.

Therapeutic shock waves generated with the Dolorclast (Source: Chitnis PV, Cleveland RO: Acoustic and cavitation fields of shock wave therapy devices. In: Clement GT, McDannold NJ, Hynynen K: CP829, Therapeutic Ultrasound: 5th international symposium on therapeutic ultrasound. 2006, American Institute of Physics.) Ogden et al. (2001): “[...] a high peak pressure, sometimes more than 100 MPa (500 bar), but more often approximately 50 to 80 MPa, a fast initial rise in pressure during a period of less than 10 ns, a low tensile amplitude (up to 10 MPa), a short life cycle of approximately 10 µs, and [...].”

Generation of therapeutic shock waves Four principles to generate therapeutic shock waves electro- hydraulic piezo-electric electro- magnetic pneumatic Ossatron Orbason Orthospec Epos Ultra Sonocur Swiss Dolorclast D-ACTOR

Therapeutic shock waves generated with the Ossatron (Source: Chitnis PV, Cleveland RO: Acoustic and cavitation fields of shock wave therapy devices. In: Clement GT, McDannold NJ, Hynynen K: CP829, Therapeutic Ultrasound: 5th international symposium on therapeutic ultrasound. 2006, American Institute of Physics.) Ogden et al. (2001): “[...] a high peak pressure, sometimes more than 100 MPa (500 bar), but more often approximately 50 to 80 MPa, a fast initial rise in pressure during a period of less than 10 ns, a low tensile amplitude (up to 10 MPa), a short life cycle of approximately 10 µs, and [...].”

Therapeutic shock waves generated with the Orthospec (Source:www.accessdata.fda.gov/cdrh_docs/pdf4/P040026b.pdf) “In order to measure the rise time and pulse duration of the shock waveform, the measurement was repeated with the oscilloscope sampling rate increased to 100 Msmp/s. From a series of measurements, the average rise time was 400±100 ns; the average pulse width was 1200+45 ns.” Ogden et al. (2001): “[...] a high peak pressure, sometimes more than 100 MPa (500 bar), but more often approximately 50 to 80 MPa, a fast initial rise in pressure during a period of less than 10 ns, a low tensile amplitude (up to 10 MPa), a short life cycle of approximately 10 µs, and [...].”

Generation of therapeutic shock waves Four principles to generate therapeutic shock waves electro- hydraulic piezo-electric electro- magnetic pneumatic Ossatron Orbason Orthospec Epos Ultra Sonocur Swiss Dolorclast D-ACTOR

Therapeutic shock waves generated with the Epos (Source: EMS, unpublished data) Energy level 5 Ogden et al. (2001): “[...] a high peak pressure, sometimes more than 100 MPa (500 bar), but more often approximately 50 to 80 MPa, a fast initial rise in pressure during a period of less than 10 ns, a low tensile amplitude (up to 10 MPa), a short life cycle of approximately 10 µs, and [...].”

Generation of therapeutic shock waves Four principles to generate therapeutic shock waves electro- hydraulic piezo-electric electro- magnetic pneumatic Ossatron Orbason Orthospec Epos Ultra Sonocur Swiss Dolorclast D-ACTOR

What are therapeutic shock waves? – Ueberle et al. (2007) Hopkins effect (Vakil 1991)

What are therapeutic shock waves? – Rompe et al. (2007) Characteristics of therapeutic shock waves (2) (Source: Rompe JD, Furia J, Weil L, Maffulli N: Shock wave therapy for chronic plantar fasciopathy. Br Med Bull 2007;81-82:183-208) Typical form of a therapeutic shock wave used in pain management

Generation of therapeutic shock waves Four principles to generate therapeutic shock waves electro- hydraulic piezo-electric electro- magnetic pneumatic Ossatron Orbason Orthospec Epos Ultra Sonocur Swiss Dolorclast D-ACTOR

Therapeutic relevant part of shock waves (1) "A significant tissue effect is cavitation consequent to the negative phase of the wave propagation." (Ogden et al., 2001) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Therapeutic relevant part of shock waves (2) „[...] Bioeffects of shock waves on nervous tissue appear to result from cavitation. It is suggested that cavitation is also the underlying mechanism of shock wave-related pain during extracorporeal SW lithotripsy in clinical medicine.” (Schelling et al., Biophys J 1994;66:133-140) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Therapeutic relevant part of shock waves (3) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Therapeutic relevant part of shock waves (4) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Focused shock waves (2)

Radial shock waves (EMS Swiss DolorClast®)

ESWT: basic physics (1) ____________________________________ Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

ESWT: basic physics (2) ____________________________________ Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Orthopaedic indications for ESWT (1) Tennis elbow (Epicondilitis humeri radialis) Subacromial pain syndrome Golfer‘s elbow (epicondylitis humeri ulnaris) Greater trochanteric pain syndrome Medial tibial stress syndrome Patellar tip syndrome Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ Achilles tendinopathy Plantar fasciopathy

Orthopaedic indications for ESWT (2) Supraspinatus tendon Common extensor tendon Patella tendon Achilles tendon Plantar fascia

RSWT®: RCTs with positive outcome Chronic plantar fasciopathy: Gerdesmeyer et al., Am J Sports Med 2008; 36: 2100-2109 Chow and Cheing, Clin Rehab 2007;21: 131-141 Greve et al., Clinics 2009; 64: 97-103 Midportion Achilles tendinopathy: Rompe et al., Am J Sports Med 2007;35:374-381 Rompe et al., Am J Sports Med 2009;37:463-470 Insertion Achilles tendinopathy: Rompe et al., Am J Bone Joint Surg 2008;90:52-61 Medial tibial stress syndrome: Rompe et al., Am J Sports Med 2009 [Epub Sep 23] Greater trochanteric pain syndrome: Furia et al., Am J Sports Med 2009;37:1806-1813 Rompe et al., Am J Sports Med 2009;37:1981-1990 Subacromial pain syndrome: Engebretsen et al., Brit Med J 2009:339:b3360 Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

ESWT: molecular and cellular mechanisms of action Wang, ISMST Newsletter 2006-03

Don’t forget neurogenic inflammation...

ESWT: molecular and cellular mechanisms of action Pain Neurogenic inflammation New bone formation ...

Substance P in periost after ESWT Clin Orthop Relat Res (2003)

ESWT: mechanisms of action (pain) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Substance P, pain and inflammation Pain afferents: myelinated or unmyelinated. Myelinated pain fibers: A-delta fibers: respond to either mechanical stimuli or temperature stimuli in the painful realm produces the acute sensation of sharp, bright pain neurotransmitter in the dorsal horn: glutamate receptor: AMPA receptors Unmyelinated pain fibers: C fibers: respond to a broad range of painful stimuli, including mechanical, thermal or metabolic factors. produce slow, burning, and long lasting pain. neurotranmitter in the dorsal horn: glutamate along with certain peptides such as substance P receptors: AMPA but also NMDA (only open following prolonged depolarization), Continual stimulation of C fibers eventually causes greater excitation in the postsynaptic neurons in the dorsal horn as the NMDA receptors start added to the response. Receptor for capsaicin: located in the C fibers (normally opened by hot stimuli). C fibers: interconnected with the process of inflammation by axon reflex (action potentials in certain branches of an afferent neuron moving peripherally). Release of substance P there increases inflammation by causing histamine release and dilation of blood vessels.

Substance P, pain and inflammation

ESWT: mechanisms of action (pain) Prolonged activation of pain and heat sensing neurons (unmyelinated C fibers) by capsaicin depletes presynaptic substance P, one of the body's neurotransmitters for pain and heat. The result appears to be that capsaicin mimics a burning sensation, the nerves are overwhelmed by the influx, and are unable to report pain for an extended period of time. With chronic exposure to capsaicin, neurons are depleted of neurotransmitters and it leads to reduction in sensation of pain and blockade of neurogenic inflammation. If capsaicin is removed, the neurons recover. Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Selective loss of nerve fibers after ESWT

Emerging results from basic research

ESWT: basic physics - cavitation Which part of shock waves mediates their biological efffects on tissue? "A significant tissue effect is cavitation consequent to the negative phase of the wave propagation." (Ogden et al., 2001) Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Activation of the G-protein coupled receptor Transcription Progression of cell cycle Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

ESWT: mechanisms of action Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ J Trauma 2008;65:1402-1410

Results of microarray studies ESWT: mechanisms of action Notizen: ____________________________________ ________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ Results of microarray studies J Trauma 2008;65:1402-1410