molecular and cellular mechanisms of radial shock wave therapy dr. christoph schmitz, md full...

Molecular and cellular mechanisms of radial shock wave therapy

Dr. Christoph Schmitz, MD

Full Professor and HeadDepartment of Neuroanatomy, Ludwig-Maximilians-University

Munich, Germany

Adjunct ProfessorDepartment of Neuroscience, Mount Sinai School of Medicine

New York, NY, USA

Medical Scientific OfficerEMS Electro Medical Systems

Nyon, Switzerland

2

Example: calcifying tendinitis of the shoulder

Vavken et al. (2009)

3

Don‘t compare apples with pies...

4

Compare within the same settings...

5

A treatment modality becomes successful when...

we know how it workswe know that it workswe know why it works

your patients become enthusiastic about it!

Enthusiastic patients – successful practice!

6

A happy patient...

7

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

8

A happy patient...

9

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

10

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 […]

11

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

12

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.

13

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."

14

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

15

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.”

16

Generation of therapeutic shock waves

piezo-electricelectro-hydraulic

electro-magnetic

pneumatic

Four principles to generate therapeutic shock waves

OssatronOrbason

Orthospec

Epos UltraSonocur

Swiss DolorclastD-ACTOR

17

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.

18

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 [...].”

19

Generation of therapeutic shock waves

piezo-electricelectro-hydraulic

electro-magnetic

pneumatic

Four principles to generate therapeutic shock waves

OssatronOrbason

Orthospec

Epos UltraSonocur

Swiss DolorclastD-ACTOR

20

Therapeutic shock waves generated with the Ossatron

(Source: Chitnis PV, Cleveland RO: Acoustic and cavitation fields of shock wavetherapy 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 [...].”

21

Therapeutic shock waves generated with the Orthospec

(Source:www.accessdata.fda.gov/cdrh_docs/pdf4/P040026b.pdf)

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 [...].”

“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.”

22

Generation of therapeutic shock waves

piezo-electricelectro-hydraulic

electro-magnetic

pneumatic

Four principles to generate therapeutic shock waves

OssatronOrbason

Orthospec

Epos UltraSonocur

Swiss DolorclastD-ACTOR

23

Therapeutic shock waves generated with the Epos

(Source: EMS, unpublished data)

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 [...].”

Energy level 5

24

Generation of therapeutic shock waves

piezo-electricelectro-hydraulic

electro-magnetic

pneumatic

Four principles to generate therapeutic shock waves

OssatronOrbason

Orthospec

Epos UltraSonocur

Swiss DolorclastD-ACTOR

25

What are therapeutic shock waves? – Ueberle et al. (2007)

Hopkins effect (Vakil 1991)

26

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

27

Generation of therapeutic shock waves

piezo-electricelectro-hydraulic

electro-magnetic

pneumatic

Four principles to generate therapeutic shock waves

OssatronOrbason

Orthospec

Epos UltraSonocur

Swiss DolorclastD-ACTOR

28

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)

29

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)

30

Therapeutic relevant part of shock waves (3)

31

Therapeutic relevant part of shock waves (4)

32

Focused shock waves (2)

33

Radial shock waves (EMS Swiss DolorClast®)

34

ESWT: basic physics (1)

35

ESWT: basic physics (2)

36

Subacromial pain syndrome

Tennis elbow (Epicondilitis humeri radialis)

Patellar tip syndrome Medial tibial stress syndrome

Achilles tendinopathy

Plantar fasciopathy

Orthopaedic indications for ESWT (1)

Golfer‘s elbow (epicondylitis humeri ulnaris)

Greater trochanteric pain syndrome

37

Orthopaedic indications for ESWT (2)

Supraspinatus tendon Common extensor tendon

Patella tendon Achilles tendon Plantar fascia

38

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

39

ESWT: molecular and cellular mechanisms of action

Wang, ISMST Newsletter 2006-03

40

Don’t forget neurogenic inflammation...

41

ESWT: molecular and cellular mechanisms of action

Pain Neurogenic inflammation New bone formation ...

42

1 2 3 4 5 6

0

500

1000

No. of eluation tubes

Su

bs

tan

ce

P (p

g/m

l)

1 2 3 4 5 6

0

25

50

75

100

125

150

175

No. of eluation tubes

Su

bs

tan

ce

P (

pg

/ml)

1 2 3 4 5 6

0

1000

2000

No. of eluation tubes

Su

bs

tan

ce

P (p

g/m

l)

six hours aftershock wave application

one day aftershock wave application

42 days aftershock wave application

Clin Orthop Relat Res (2003)

Substance P in periost after ESWT

43

ESWT: mechanisms of action (pain)

44

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.

45

Substance P, pain and inflammation

46

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.

47

Selective loss of nerve fibers after ESWT

48

Emerging results from basic research

49

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)

50

Activation of the G-protein coupled receptor

TranscriptionProgression of cell cycle

51

52

ESWT: mechanisms of action

J Trauma 2008;65:1402-1410

53

ESWT: mechanisms of action

J Trauma 2008;65:1402-1410

Results of microarray studies