Collagen medical device

From the theory to the “real-world practice”

When to intervene with injectable collagen?

Which are the fields of application of injectable collagen?
Panorama on clinical applications in Pain Management

Joint Disease
Tendinopathy
Low Back Pain
Myofascial Pain Syndrome

Which are the injective techniques to apply?

Nicola Alfieri MD
Physiatrist
Sports Medicine Specialist

nicola.alfieri@gmail.com
• Since 2010 the treatment of algic/degenerative
diseases of the musculoskeletal system takes
advantage of the use of the injectable Collagen
Medical Device
• Collagen (type I) + natural support components

• The Collagen MDs are applied locally through:

• peri-articular injections
• intra-articular injections
• intra-muscular injections
• subcutaneous and/or intradermal injections
 In this speech I am going to show you the
possibility of Collagen Medical Devices in 4
pathologies that are frequent in the daily
clinical practice:

Joint Disease
Tendinopathy
Low Back Pain
Myofascial Pain Syndrome
• Composition:
• collagen type 1
• tangential filtration
• sterilization
• contaminant-free
• standardized chemical and physical characteristics
• molecular weight control
• excipients
• ancillary components
• NaCl, water for injection (isotonic)
• SKA technology ensures high solubility and diffusion
properties in biological water and extracellular fluids
 The assembly of collagen fibrils
from tropocollagen molecules.

Uchena N. G. Wudebwe et al. Phil. Trans. R. Soc. B

2015;370:20140200

©2015 by The Royal Society

 The evolution of multicellular
organisms depended on the
formation of an extracellular matrix.
Collagen fibrils, which can be several
millimetres in length, have played a
central role in extracellular matrices for
at least 500 million years.
Current evidence suggests that
collagen fibril formation is Microrheological Characterization of
intrinsically a self-assembly process Collagen Systems: From Molecular
Solutions to Fibrillar Gels.
but that considerable cellular control is PLoS ONE 8(8): e70590. 2013
exerted on the process in vivo
 Collagens self-assemble into fibrils

Myers TW. Meridiani

miofasciali. Milano:
Tecniche nuove,
2006

B0005968 Credit Rob Young, Wellcome Images

Collagen fibril forming in vitro
A collagen fibril forming in a test tube from a solution of purified collagen protein. The new molecules arrange themselves at
the tip of the fibril in a very organised way. The result of the precise alignment of the individual collagen molecules is the
typical pattern of light and dark bands across the fibril. This self-assembly is a naturally occurring process like those exploited
in various forms of nanotechnology. Collagen forms the basis of a lot of the connective tissue in the body and is becoming
increasingly popular as a cosmetic treatment for filling out wrinkles, lips and old scars.
Transmission electron micrograph
Collection: Wellcome Images
Copyrighted work available under Creative Commons by-nc-nd
 Collagen fibers are mainly composed of the collagen protein and arranged in
bundle or reticular form. It is the main protein composition in the extracellular
matrix of the connective tissue. From the perspective of biomechanics,
collagen is a three-dimensional long-range ordered structure, with the nature
of liquid crystalline continuum.

Collagen
network

B0006128 Credit David Gregory&Debbie Marshall, Wellcome Images

Collagen network
Colour-enhanced scanning electron micrograph of a network of collagen.
Scanning electron micrograph 2005
Collection: Wellcome Images

Copyrighted work available under Creative Commons by-nc-nd 2.0 UK: England & Wales, see http://images.wellcome.ac.uk/indexplus/page/Prices.htm
 Extracellular Matrix
• The ECM is a
conglomerate of
substances in which
biochemical and
biophysical properties
allow for the construction
of a flexible network
that integrates
information from loading
and converts it into
mechanical capacities
• Kjaer M. Role of extracellular matrix in adaptation
of tendon and skeletal muscle to mechanical
loading. Physiol Rev 2004, 84, 649–698.
 TYPE 1 COLLAGEN DIFFUSION:

SKA technology ensures high solubility and diffusion

properties in biological water and extracellular fluids

© Dipartimento Scientifico Guna S.p.a.

Cells 2018, 7, 246; doi:10.3390/cells7120246
GUNA Collagen Medical
Devices
Extracellular Matrix Bioscaffolds
Tissue- and site-specific
Collagen Medical Device
Collagen Medical Device
Collagen Medical Device
 I’ll also explain the concept of
overlapping therapy that allows
the use of Collagen Medical
Devices in association with other
treatments
Multimodal therapy
 Collagen Medical Device
Type of Injection

peri-articular injections

intra-articular injections
(obviously in the joints allowing a clear intra-articular approach:
knee, hip, shoulder)

peri-tendinous injections

subcutaneous and/or intradermal injections

(in spontaneously painful points, in points where average
digitopressure causes pain, in local acupuncture points, etc.)

intramuscular injections
(into muscle trigger points)
 Type of Injection

Pain points Intradermic

PP ID

Subcutaneous
Cutaneous SC
Ligamentous
Entheseal Intramuscolar
Muscle IM

Intra-articular
IA
Peri-articular Epidermis
PA
Dermis

Acupuncture Subcutaneous
tissue

points
Muscle
 Needles size

4 mm
13 mm
25 mm

27 G 30 mm
27 G 40 mm
30 G
HRUS Image of Normal Skin
EPISCAN Images showing a Tendon
Achilles Tendinopathy

CMAJ, July 12, 2011, 183(10)

37
Achilles Tendinopathy

38
Knee Surg Sports Traumatol Arthrosc (2010) 18:638–643 39
 Achilles Tendon Injection

Anatomy:
The achilles tendon lies at the end of the gastrocnemius as it inserts into the posterior surface of
the calcaneus.ure.

Technique:
• Patient lies prone with foot held in dorsiflexion over end of bed. This keeps the tendon under
tension and facilitates the procedure
• Identify and mark tender area of tendon - usually along the sides
• Insert needle on medial side and angle parallel to tendon. Slide needle along side of tendon,
taking care not to enter into tendon itself
• Deposit half solution while slowly withdrawing needle
• Insert needle on lateral side and repeat procedure with remaining half of solution
 MD
TISSUE
The depth of the Achilles tendon
from the skin was 2.2 +/- 0.3
mm at its superficial surface and
7.8 +/- 0.4 mm at its deep
surface.
 Different Kinds of
Injections for different
disease
Periarticular - Knee Osteoarthritis

Peritendinous - Shoulder Tendinopathy

Intradermal - Low Back Pain

Trigger point - Myofascial pain

syndrome
 Different Kinds of Injections
for different disease
Periarticular - Knee Osteoarthritis
MD Tissue + MD Knee

Peritendinous - Shoulder Tendinopathy

MD Tissue + MD Shoulder

Intradermal - Acute Low Back Pain

MD Lumbar + MD Muscle/Neural

Trigger point - Myofascial pain

syndrome
MD Muscle
Osteoarthritis
 The most common target joint
affected by osteoarthritis is the knee
joint
Sources of pain include intra-articular
and supportive extra-articular
structures.

Nature Reviews Drug Discovery 4, 331-344 (April 2005)

 Pain is a protective mechanism, not necessarily a symptom of damage

f joint pain are widely variable even in patients with similar ra

 Osteoarthritis (OA)
• OA is a syndrome and not a disease defined by the degenerative changes in the joint.

• OA is often described as ‘wear and tear’ but this is not an accurate reflection of the
pathogenesis of OA.

• OA is a metabolically active process which, in response to various insults,

involves all joint tissues: cartilage, bone, synovium, ligaments and muscles.
• OA is not a one-way process that will get worse with time

• A better representation of the development of OA is ‘tear, flare and repair’:

• Tear – representing aetiological factors such as overuse, obesity or malalignment

• Flare – the role of inflammation in OA

• Repair – repair processes in and around the joint. These repair processes can
lead to a structurally altered but symptom-free joint. However, the repair
processes may be suboptimal, and the ‘tear’ insults may be ongoing, resulting in
the symptomatic OA with persistent pain and disability.

Fraser Birrell. Nick Howells, Mark Porcheret

Osteoarthritis: pathogenesis and prospects for treatment
Reports on the Rheumatic Diseases (Series 6), Hands On 10. Arthritis Research
UK; 2011 Autumn.
 Current osteoarthritis
treatment options

Nature Reviews Drug Discovery 4, 331-344 (April 2005)

All innervated tissues inside and around the knee joint are
potential pain generators in knee OA
Not only intra- but also extra-articular pathology should be
targeted.
Extra- and intra-articular structures consist
basically of collagen
 MD Collagen injections target multiple
potential pain generators around the knee
joint; it may be well-suited to address the
multifactorial cause of knee pain from
osteoarthritis.
J Bone Joint Surg Am, 2003 Jun; 85 (6): 1012 -1017
of joint pain are widely variable even in patients with similar r

injections target multiple potential pain generators around

Structurally altered but symptom-free joint

PAIN
Algofunctional Index
Joint swelling, sonographically assessed
 Authors’
•
conclusions
Collagen MD
1. reduces significantly pain at rest and during
movement and improves the functional activity of
patients.
2. the effectiveness of treatment was evaluated as
excellent + good in 68% of patients and 72% of
physicians.
3. Periarticular edema improves in 90% of cases as
proven by ecography.
4. The effect is maintained even after treatment.
5. The analysed MDs have a very high safety profile
 Reduced thickness of the subcutaneous tissue at the joint
region and proximity to the tissues of the ligaments ensures an
efficient tropocollagen diffusion in the periarticular district

Bursa Epidermis / dermis

Tendon

Subcutaneous tissue
 in MD-KNEE the ancilliary substance is Arnica that
has a modulating action of the inflammatory process
“Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB.”
Lyss G. et al. Biol Chem. 1997
CELL GROWTH COLLAGEN TURNOVER MIGRATION

cell proliferation COL-I synthesis cell migration

COL-I degradation
 “Helenalin, an anti-inflammatory
sesquiterpene lactone from Arnica, selectively
inhibits transcription factor NF-kappaB.”
Lyss G. et al. Biol Chem. 1997

ELENALINA

SAGGIO IN VITRO
PER VALUTARE
NF- L’INIBIZIONE DEL
kB MARKER
PROINFIAMMATORIO
NF-kB

Lyss G. et al. The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by
directly targeting p65. J Biol Chem. 1998
© Dipartimento Scientifico Guna S.p.a.
Knee Osteoarthritis
MD Knee + MD Tissue

Needle size: 30G 13 mm

Periarticular administration

During the first 2 weeks - 2 applications per

week
during the next 6 weeks - 1 application per
week
 Overlap Therapy
Knee Osteoarthritis

Comprehensive management of osteoarthritis should include a

combination of treatment options directed toward the goals of alleviating
pain and improving function.

The recommended hierarchy of management includes

nonpharmacologic methods (weight loss, exercise, braces, and assistive
devices), analgesic medicine (including nonsteroidal anti-inflammatory
drugs [NSAIDs]), and local injection treatment

Peri-articular Collagen MD
Intra-articular?
 JOINT

A double blind randomized active-

controlled clinical trial on the intra-articular
use of Md-Knee versus sodium
hyaluronate in patients with knee
osteoarthritis (“Joint”)
77
 Diagram showing the lateral midpatellar
portal. P = patella, F = femur, T = tibia, and
FP = fat pad.

78
79
Patellar Tendinopathy
 MD
TISSUE

81
Anatomy of the medial collateral ligament
 Pes Anserine

Sartorio
Gracile
Semitendinoso

MD
TISSUE
83
Ilio-Tibial Band
MD
TISSUE

84
Lateral Collateral Ligament
Ligamentous Trigger Point

MD
TISSUE

85
 Ankle Sprain

Grade 1 Grade 2 Grade 3

• Ligament is stretched • Ligament is partially torn • Ligament is completely
• Minimal pain & • Some pain & swelling torn
swelling • Some functional • Severe pain & swelling
• Minimal functional impairment • Severe functional
impairment • Some weight bearing impairment
• No weight bearing difficulties • Almost complete weight
difficulties bearing difficulties

86
Anatomy of the lateral ligaments of the ankle
 MD
TISSUE
89
 Anterolateral aspect of the ankle
joint.
AT, Achilles tendon;C, calcaneus;
DCSPN, dorsal cutaneous branch
of the superficial peroneal nerve;
Fi, fibula; JL, joint line; PT,
peroneal tendons; SuN, sural
nerve.

Anatomy of the ankle

(1) Sural nerve
(2) Superficial peroneal nerve
Plantar Fasciopathy

91
 Plantar Fasciopathy
Plantar fasciopathy is a common disorder that generally affects individuals in the fourth to fifth decades. There are several
underlying conditions or associations, including an increase in the body mass index and occupations that involve prolonged
standing or marching such as in military personnel. Most notable among the medical conditions that can predispose to
plantar fasciopathy is diabetes mellitus, but systemic enthesopathy such as with seronegative arthritides and rheumatoid
arthritis are also important. Other associated predisposing factors include chemotherapy, retroviral infection, and, rarely,
gonococcus and tuberculosis infection.

Semin Musculoskelet Radiol 2010;14:334–343

92
Plantar Fasciopathy

93
Plantar Fasciopathy

94
 MD
TISSUE
 Ligaments and Tendons

• Dense connective tissue

• Hypocellular and Hypovascular

• Collagen 70% - 80% of the dry weight

• Collagen fibrils, which are the subunits of collagen, are

drowned into the extra-cellular matrix

• Fibroblasts are the predominant cell type

• Hsu et al., Functional tissue engineering of ligament healing Sports Medicine, Arthroscopy,
Rehabilitation, Therapy & Technology 2010, 2:12
Collagen fibres - Fibroblast

Hsu et al., Functional tissue engineering of ligament

healing Sports Medicine, Arthroscopy,
Rehabilitation, Therapy & Technology 2010, 2:12

B0002682 Credit Kate Whitley, Wellcome Images

Fibroblast showing actin cytoskeleton - purp
3T3 cell (fibroblast) growing in culture. It shows
the actin cytoskeleton in purple.
Confocal micrograph
Collection: Wellcome Images
Library reference no.: Contributor Reference 3T3D2

Copyrighted work available under Creative Commons by-nc-nd 2.0 UK: England & Wales, see
http://images.wellcome.ac.uk/indexplus/page/Prices.html
B0008289 Credit Anne Weston, LRI, CRUK, Wellcome Images
Connective tissue
False-coloured scanning electron micrograph of collagen/connective tissue removed from a human knee during arthroscopic surgery.
Scanning electron micrograph 2011
Collection: Wellcome Images

Copyrighted work available under Creative Commons by-nc-nd 2.0 UK: England & Wales, see http://images.wellcome.ac.uk/indexplus/page/Prices.html
 Hierarchical structure of tendon
• As an aligned fibre composite
material, the hierarchical structure
of tendon enables it to withstand
high tensile forces, but results in
complex anisotropic and
viscoelastic characteristics.
• The mechanical properties of
tendon as a whole are
determined by the composition
and organization of the matrix at
each structural level and the way in
which they contribute in response to
tensile loading.
• Thorpe C T et al. J. R. Soc. Interface
doi:10.1098/rsif.2012.0362
Response of tendon and skeletal
muscle tissue to unloading

Hindlimb
suspension

Heinemeier KM et al. J Appl Physiol 106:178-186, 2009.

Tendons and ligaments healing

• After injuries tendons and ligaments heal much slower

than other soft tissues because of their hypocellularity
and hypovascularization.
• For extra articular ligaments, such as MCL, the healing
is spontaneous and classically in 4 phases
(haemorragic, inflammatory, proliferative, remodelling).

• For intra-articular ligaments some enviromental limits

make healing more difficult.
• Hsu et al., Functional tissue engineering of ligament healing Sports Medicine, Arthroscopy,
Rehabilitation, Therapy & Technology 2010, 2:12
Tendons and ligaments healing
 Cell-matrix response in
tendon injury

• Inflammatory
phase
• Reparative
phase
• Remodelling
phases
(consolidation
and maturation)
 Inflammation
• One of the most
common mistakes in
the treatment of arthro-
myo-fascial pathologies
is excessive use of anti-
inflammatory drugs
during acute phases or
continuous use of these
drugs in chronic
disorders.
 Tendinopathy
paradigm

• Painful, overuse
tendon conditions
have a non-
inflammatory
pathology

Millar NL et al. Inflammation is present in early human

tendinopathy. Amer J Sorts Med, 2010;38(10):2085-91.
Tendinopathy
Ten of 11 readily available sports medicine texts specifically recommend nonsteroidal
antiinflammatory drugs for treating painful conditions like Achilles and patellar
tendinitis despite the lack of a biological rationale or clinical evidence for this
approach.
Instead of adhering to the myths above, physicians should acknowledge that painful
overuse tendon conditions have a noninflammatory pathology.
Animal studies show that within two to three weeks of tendon insult tendinosis is present
and inflammatory cells are absent.
A critical review of the role of various antiinflammatory medications in soft tissue
conditions found limited evidence of short term pain relief and no evidence of their
effectiveness in providing even medium term clinical resolution of clearly diagnosed
tendon disorders. Laboratory studies have not shown a therapeutic role for these
medications.
Corticosteroid injections provide mixed results in relieving the pain of tendinopathy.
If general practitioners treating musculoskeletal conditions embraced the tendinopathy
paradigm, it would provide patients with an accurate description of their condition. It
would avoid inappropriate pharmacotherapy with its attendant costs and
comorbidity.
Furthermore, by accepting need to allow time for collagen turnover and remodelling
inherent in the pathology of tendinosis, doctors would be free to provide patients with a
realistic prognosis that better reflects the finding of prospective clinical studies.These
conditions take months rather than weeks to resolve.
 Tendinopathy
Treatments

Journal of Sports Science and Medicine (2011) 10, 238-253

 Tendinopathy
Treatments

Journal of Sports Science and Medicine (2011) 10, 238-253

 Movement is essential for tendons
J Musculoskelet
Neuronal Interact Transduction of mechanical
2011; 11(2):115-123
force into biochemical
events
Intake of NSAID results in a
diminished exercise induced
increase in collagen
synthesis
Markers of collagen synthesis
(PINP)

J Appl Physiol
110:137-141,
2011.
growth factor-β-1 (TGF-β-1)
connective tissue growth factor (CTGF)
insulin like growth factor-I (IGF-I)
IL-6
Intake of NSAID results in a diminished
exercise induced increase in collagen
synthesis
Markers of collagen synthesis (PINP)

J Appl Physiol 110:137-141,

2011.
Intake of NSAID results in a diminished
exercise induced increase in collagen
synthesis

J Appl Physiol 110:137-141,

2011.
• Therefore, we can assert that
NSAIDs:

• are useless in chronic

tendinopathies, as the inflammatory
factor is almost absent

• are harmful during rehabilitation, as

they inhibit the collagen synthesis
 Tendon Healing

Rehabilitative exercise

Collagen MD

Physical
Therapy
RICE Millar NL et al.
Painful, overuse tendon conditions
FAN Inflammation is present in early human
tendinopathy. have a non-inflammatory pathology
S Amer J Sorts Med, 2010;38(10):2085-91.
 Pain

EUROPEAN JOURNAL OF MUSCULOSKELETAL DISEASES Vol. 3, no. 1, 15-23 (2014)

CLINICAL AND SONOGRAPHIC ASSESSMENT OF THE EFFECTIVENESS OF COLLAGEN INJECTIONS GUNA MDs IN SHOULDER PERIARTHRITIS WITH BURSITIS
NESTOROVA R1, RASHKOV R2, RESHKOVA V2
 Shoulder Function Assessment

EUROPEAN JOURNAL OF MUSCULOSKELETAL DISEASES Vol. 3, no. 1, 15-23 (2014)

CLINICAL AND SONOGRAPHIC ASSESSMENT OF THE EFFECTIVENESS OF COLLAGEN INJECTIONS GUNA MDs IN SHOULDER PERIARTHRITIS WITH BURSITIS
NESTOROVA R1, RASHKOV R2, RESHKOVA V2
 US

EUROPEAN JOURNAL OF MUSCULOSKELETAL DISEASES Vol. 3, no. 1, 15-23 (2014)

CLINICAL AND SONOGRAPHIC ASSESSMENT OF THE EFFECTIVENESS OF COLLAGEN INJECTIONS GUNA MDs IN SHOULDER PERIARTHRITIS WITH BURSITIS
NESTOROVA R1, RASHKOV R2, RESHKOVA V2
 Authors’ conclusions
• Collagen MD:
1. Help strengthen and regenerate the collagen
structures and improve significantly the shoulder
pain and the functional status as well as the tension
of the subdeltoid bursa.
2. The efficacy of the tested Collagen MDs continues
to last after the end of treatment, and improves the
patients’ quality of life.
3. The Collagen MDs have shown to be completely
safe (no side effects).
EUROPEAN JOURNAL OF MUSCULOSKELETAL DISEASES Vol. 3, no. 1, 15-23 (2014)
CLINICAL AND SONOGRAPHIC ASSESSMENT OF THE EFFECTIVENESS OF COLLAGEN INJECTIONS GUNA
MDs IN SHOULDER PERIARTHRITIS WITH BURSITIS
NESTOROVA R1, RASHKOV R2, RESHKOVA V2
 Shoulder
Tendinopathy
MD Shoulder + MD Tissue

Needle size: 27G 40 mm

Peritendinous - Periarticular

During the first 2 weeks - 2 applications per

week
during the next 6 weeks - 1 application per
week
2012;94-B:1246–52
Subacromial Injection - Posterior
Approach

126
Subacromial Injection - Lateral
Approach

127
 Overlap Therapy
Shoulder Tendinopathy

Comprehensive management of tendinopathy should include a

combination of treatment options directed toward the goals of alleviating
pain and improving function.
The recommended hierarchy of management includes nonpharmacologic
methods (eccentric training, passive physiotherapy), analgesic medicine,
and local injection treatment

Rehabilitative exercise + injection with Collagen MD

130
Anatomy of the rotator cuff
 Supraspinatus Tendon

Anatomy
The supraspinatus tendon inserts into the superior facet on the greater tuberosity of the humerus,
which lies in a direct line with the lateral epicondyle of the elbow. A line joining the two points
passes through the tendon, which is approximately the size of the middle finger at insertion.
Technique
• Patient sits supported at about 45° with forearm medially rotated behind back, bringing the
tendon forward so it lies just anterior to the edge of the acromion
• Identify rounded tendon in the hollow between acromion and tuberosity, in direct line with the
lateral epicondyle
• Insert needle perpendicularly through tendon to touch bone
• Pepper solution perpendicularly into tendon
 Muscular and tendinous geometry of the supraspinatus and infraspinatus. A: Photograph of the superior aspect of a right shoulder, showing the myotendinous
unit of the supraspinatus. B: Photograph of the dorsal aspect of a right shoulder, showing the myotendinous unit of the infraspinatus. C: Photograph of the
superior aspect of a right shoulder, showing the tendinous portion of the supraspinatus. The supraspinatus tendon is composed of two portions: the anterior half
is long and thick (SSP-LT), and the posterior half is short and thin (SSP-ST). D: Photograph of the dorsal aspect of the same specimen, showing the tendinous
portion of the infraspinatus. The superior half of the infraspinatus tendon is long and thick (ISP-LT), while the inferior half is short and thin (ISP-ST). The
tendinous insertion of the supraspinatus takes up only the anteriormost portion of the greater tuberosity, while the insertion of the infraspinatus occupies most of
the greater tuberosity. The border between the infraspinatus and teres minor is indicated by the black line. CP = coracoid process, SS = scapular spine, SSP
= supraspinatus, ISP = infraspinatus, TMi = teres minor, TMi-T = tendinous portion of the teres minor, Ant = anterior, Med = medial, and Sup =
superior.
 Acromioclavicular Joint

Anatomy:
The acromioclavicular joint line runs in the sagittal plane about a thumb's width medial to the
lateral edge of the acromion. The joint plane runs obliquely medially from superior to inferior and
usually contains a small meniscus. Often a small step can be palpated where the acromion abuts
against the clavicle, or a small V-shaped gap felt at the anterior joint margin. Passively gliding
the acromion downwards on the clavicle may help in finding the joint line.

Technique:
• Patient sits supported with arm hanging by side to slightly separate the joint surfaces
• Identify lateral edge of acromion. Move medially about a thumb's width and mark mid-point of
joint line
• Insert needle angling medially about 30° from the vertical and pass through capsule
• Inject solution as a bolus
 MD
TISSUE
 Low Back Pain
• Low back pain is pain,
muscle tension, or
stiffness, localised
below the costal
margin and above the
inferior gluteal folds,
with or without referred
or radicular leg pain
(sciatica), and is
defined as acute when
pain persists for <12
weeks.
Clinical Evidence2011;05:1102
Acute Low Back Pain
• Low back pain affects about 70% of people in
resource-rich countries at some point in their
lives.
• About 19 in 20 cases of sudden-onset (acute)
low back pain are classed as nonspecific.
• Acute low back pain may be self-limiting,
although there is a high recurrence rate with
less-painful symptoms recurring in 50% to 80%
of people within 1 year of the initial episode; 1
year later, as many as 33% of people still
experience moderate-intensity pain and 15%
experience severe pain.
Clinical Evidence2011;05:1102
 Many treatments are
available for acute low
back pain…
• NSAIDs have been shown to effectively improve symptoms
compared with placebo. However, their use is associated with
gastrointestinal adverse effects.
• Muscle relaxants may also reduce pain and improve overall
clinical assessment, but are associated with some severe adverse
effects including drowsiness, dizziness, and nausea.
• The studies examining the effects of analgesics such as
paracetamol or opioids were generally too small to detect any
clinically important differences.
• With regard to non-drug treatments, advice to stay active (be it
as a single treatment or in combination with other interventions
such as back schools, a graded activity programme, or behavioural
counselling) may be effective.

Clinical Evidence2011;05:1102
 Local therapy in
Acute Low Back Pain
• Among the various attempts to reduce
drug toxicity, the use of local therapy
(neural block, intraarticular, or
periarticular injections of corticosteroids)
has gained popularity among physicians,
despite some controversies concerning its
efficacy as a therapeutic remedy
• One of the treatment options is local
injection with collagen Medical Device.
 Collagen MD in
Acute Low Back Pain
Clinical trial FUTURE
• Clinical trial FUTURE (Edukafarm - GUNA - Italy)

• Single-blinded randomized clinical trial

evaluating efficacy and safety of MD–
Lumbar, MD-Muscle and MD-Neural vs.
Trimecain (Mesocain) s.c. in patients with
acute LBP
• Prof. K. Pavelka, M.D., Ph.D. Director of the Institute of
Rheumatology, Charles University, Prague

• Protocol No. 27109640, EudraCT number: 2011-001888-51

• Interim analysis of the first 48 patients

 Collagen MD in
Acute Low Back Pain
Clinical trial FUTURE
• Methods
• Group A / Group B: patients ratio 3:1
• Group A n = 73
• MD-Lumbar + MD-Muscle + MD-
Neural s.c. into 8 predefined
paravertebral points
• Group B n = 24
• Trimecaini hydrochloridum 1 %
• 5 inj. application during 3 weeks
• Rescue medication: paracetamol < 3
g/day
 PAVELKA K., SVOBODOVÁ R., JA- ROŠOVÁ H.

Institute of Rheumaology, Charles University, Prague

MD-LUMBAR, MD-MUSCLE AND MD-NEURAL IN THE TREATMENT OF LOW BACK PAIN

PHYSIOLOGICAL REGULATING MEDICINE 2012/1; 3-6

number of
applications: 5
(2/weeks + 1).
 Collagen MD in
Acute Low Back Pain
Clinical trial FUTURE
• Primary endpoints
• To compare effects of collagen injections vs. trimecaine on
pain intensity of acute LBP
• Evaluation of time period needed to alleviate pain.
• Secondary endpoints
• Evaluation of pain intensity and its effect on functional
status and quality of life
• Evaluation of rescue medication needs - paracetamol
• Evaluation of the treatment post 2-weeks follow-up
• Evaluation of tolerability
Acute Low Back Pain
MD Lumbar + MD Muscle + MD Neural
MD-Lumbar + MD-Neural: low back pain with algic nerve imprint
MD-Lumbar + MD-Muscle: low back pain with prevailing myo-fascial
imprint

Needle size: 30G 13 mm

Local injections

During the first 2 weeks - 2 applications per

week
next week - 1 application
 In addition to collagen, MD-Lumbar contains an extract from the bark and roots of
the medicinal plant Hamamelis virginiana. The active ingredients of this extract are
tannins, organic acids and essential oils; the extract has anti-inflammatory and
antioxidant effects. It protects tissues at the injection site from the development of
the inflammatory process that occur secondary to degenerative changes of the
connective tissue; this inflammation further damages the tissues affected by
degeneration. The anti-inflammatory effect of the extract from Hamamelis
virginiana thus contributes to the effect of collagen. The extract, in addition to its
antioxidative action, protects the integrity of tissues at the application site from the
effects of harmful oxygen radicals.
MD-Neural is a medical device designed primarily to suppress neuropathic pain in
different locations via its effect on the collagen component of the perineurium. In
addition to collagen, it contains an extract from the medicinal plant Citrullus
colocynthis. The extract from this plant is used in low concentration dilution in
traditional medicine as a spasmolytic and analgesic. The analgesic effects of the
ingredients (e.g. bitter compounds, triterpenes, and resins) are used in neuropathic
pain, i.e. the stabbing pain typical for lumbago and sciatica.
MD-Muscle is a medical device which acts as an analgesic due to its effect on
muscle tissue. In addition to collagen, it contains an extract from the medicinal
plant Hypericum perforatum. Besides showing antidepressant action, this extract
has anti-inflammatory and analgesic effects. It contains the full spectrum of active
ingredients (e.g. hypericin, hyperforin, tannins, flavonoids) with anti- inflammatory,
analgesic and regenerative effects. Its analgesic effects can be useful in cases of
neuropathic and muscle pain.
Physiol. Res. 68 (Suppl. 1): S000-S000, 2019
 Overlap Therapy
acute LBP

Comprehensive management of acute LBP should include a combination

of treatment options directed toward the goals of alleviating pain, improving
function, reduce time taken to return to work and prevent the development
of chronic back pain

The recommended hierarchy of management includes nonpharmacologic

methods (advice to stay active, exercise and manual treatment), FANS, and
local injection treatment

Exercise and manual treatment + Local injection with

Collagen MD
 Shortened
Muscle
Syndrome
Shortening of the paraspinal muscles
(particularly the multifidi muscles)
innervated by dorsal ramus of
affected segmental nerves leads to
disk compression and narrowing of
the intervertebral foramina, or direct
pressure on the nerve root, which
subsequently results in peripheral
neuropathy and the development of
supersensitive nociceptors and pain.

mulation (IMS), Pain and Treatment, Dr. Gabor Racz (Ed.), ISBN: 978-953-51-1629-5, InTech, DOI: 10.5772/58565. Available from: http://www.intechopen.
 Clinical Signs
Pilomotor reflex - Matchstick test - Peau d’orange effect - Skin rolling test
 Fascia

Langevin et al. BMC Musculoskeletal Disorders 2011,

12:203
 Fascia

Myers TW. Meridiani

F. H. Willard et al. J. Anat. (2012) doi 10.1111/j.1469- miofasciali. Milano:
7580.2012.01511.x Tecniche nuove,
2006
Fig. 6 These are posterior views of the paraspinal muscles in the lumbosacral region. (A) The
PLF has been removed to expose the iliocostalis lumborum (IcL) and the longissimus thoracis
(LoT), as well as the aponeurosis of these two muscles (apo ES). A narrow rim of the deep
lamina (dPLF) is seen at the point where the apo ES and the overlying TLF fuse to form the
thoracolumbar composite (TLC). This fusion occurs at or slightly above the level of the
posterior superior iliac spine (PSIS). (B) Erector spinae muscles of the lumbar region, IcL and
LoT, have been removed to expose the more medially positioned multifidus lumborum
(MuL). The opaque white bands (arrow) on the posterior surface of the MuL represent regions
where the muscle bands fused with the inner aspect of the overlying apo ES. GM, gluteus
maximus.
 Gunn CC.
The Gunn approach to the treatment of chronic pain.
Churchill Livingstone 1997
Collagen Medical
Devices
MD Neck
MD Muscle

MD Thoracic

MD Neural
MD Lumbar
 Injection points of a single mesotherapic treatment. Drug injections were
administered along the running of sciatic nerve, through specific needles (30 G
× 4 mm)

Evidence-Based Complementary and Alternative

Medicine 2011doi:10.1155/2011/317183
• Composition:
• collagen type 1
• tangential filtration
• sterilization
• contaminant-free
• standardized chemical and physical characteristics
• molecular weight control
• excipients
• ancillary components (Hypericum Perforatum)
• NaCl, water for injection (isotonic)
• SKA technology ensures high solubility and diffusion
properties in biological water and extracellular fluids
Group I was injected into the masseter
trigger points using 2ml of Collagen MD
MD Muscle (Guna, Italy) MUSCLE
Group II 2ml of 2% Lidocaine
(Lignocainum hydrochloricum WZF,
Polfa Warsaw, Poland) without
vasoconstrictor, and Group III 2 ml of
saline as a control (0.9% NaCl) at 2nd
and 3rd visits.
In all groups, disposable syringes (2ml)
and needles (0.4×19mm) were used
for injections.

During the intervention, trigger points

within masseter muscles were
identified with palpation of the
masseter muscle, and each group was
injected with the same amount of the
appropriate substance (2ml) into the
trigger point structure.
Injections were deposited
approximately 1–1.5 cm under the skin
surface.
Temporomandibular Joint
Muscle is the largest organ
in the body

Guyton & Hall – Textbook of Medical Physiology. 10th Ed. P.67.

 Approximately 40% of the human
body is comprised of skeletal muscle

Guyton & Hall – Textbook of Medical Physiology. 10th Ed. P.67.

 Myofascial pain syndrome is a
common cause of pain and
dysfunction in the musculoskeletal
system that accounts for 20% to 95%
of patients with musculoskeletal pain
complaints

Myofascial pain syndrome. OrthopaedicsOne Articles. In: OrthopaedicsOne - The Orthopaedic Knowledge Network. Created Oct
20, 2011 14:35. Last modified Jun 28, 2012 13:26 ver.5. Retrieved 2016-10-29, from http://www.orthopaedicsone.com/x/8ABCB.
Myofascial trigger points are the
most common, yet misdiagnosed
and inadequately treated
component of non-articular
musculoskeletal pain disorders

THE PAIN PRACTITIONER | SUMMER 2012

Vol 22 n 2 26-33
 Myofascial trigger points produce
functional consequences in terms of
a restriction of range of movement
and weakness (probably a reflex
inhibition secondary to pain) which is
usually associated to easy
fatigability of the involved muscle

Best Practice & Research Clinical Rheumatology Vol. 21, No. 3, pp. 427–445, 2007
 Myofascial Pain Syndrome
=
Shortened Muscle Syndrome
Shortened Muscle

Gunn CC.
The Gunn approach to the treatment of chronic pain.
Churchill Livingstone 1997
Shortened Muscle

Gunn CC.
The Gunn approach to the treatment of chronic pain.
Churchill Livingstone 1997
Shortened Muscle

Gunn CC.
The Gunn approach to the treatment of chronic pain.
Churchill Livingstone 1997
Myofascial Release Therapy
focuses on releasing muscular
shortness and tightness
Deep dry needling
 Superficial dry needling

Baldry recommended
inserting an acupuncture
needle into the tissues
overlying each trigger point
to a depth of 5 to 10 mm
for 30 seconds
 Pain arising from muscle is a
more powerful stimulus for
central sensitization than pain
arising from skin

Best Practice & Research Clinical Rheumatology Vol. 21, No. 3, pp. 427–445, 2007
 Segmental paraspinal
muscle spasm
Superficial dry needling
should be performed not
only in muscle at the site of
pain but also in the
paraspinal muscles of the
same spinal segment that
innervates the painful
muscles (according to
Gunn’s approach)
MD Neck

MD Lumbar
Trigger Point
 Deep dry needling is one of the
alternative treatment modalities for
these patients who do not respond to
superficial needling
J Orthop Sports Phys Ther 2013;43(9):635. doi:10.2519/jospt.2013.0505
Trigger Point

MD
MUSCLE
Trigger Point
(Travell e Simons)
 MD
MUSCLE
Myofascial
Pain Syndrome
Trigger point infiltration
MD Muscle
Needle size: 30G 13mm/25mm, 27G 40mm

one weekly until symptoms disappear

according to the clinical experience, pain
symptomatology and movement improves after first
session
 Trigger point injections should
be performed not only in
muscle at the site of pain but
also in the paraspinal muscles
of the same spinal segment that
innervates the painful muscles
(according to Gunn’s approach)
 Example of
Collagen MD
Multitarget Therapy
Tennis Elbow

Shortened
Muscle
Causal
Chain

Gunn CC.
The Gunn approach to the
treatment of chronic pain.
Churchill Livingstone 1997
 Muscles, Ligaments and Tendons Journal 2019;9 (4

MD
TISSUE
Lateral Epicondyle Tendinopathy

MD
TISSUE

201
 “Intramuscular Stimulation for Myofascial Pain
of Radiculopathic Origin”
CC. Gunn

Caus
al
Chain
 THE LANCET
Volume 376, Issue 9754, Pages 1751 - 1767, 20 November 2010
 CORTICOSTEROIDS
short-term gain for long-term pain?
Shortened Muscle
Tennis Elbow

MD
NECK

Caus
MD
al
TISSUE
Chain
MD
MUSCLE Gunn CC.
The Gunn approach to the
treatment of chronic pain.
Churchill Livingstone 1997
Myofascial Meridians

Myers TW. Meridiani

miofasciali. Milano:
Tecniche nuove,
2006
 MD
MUSCLE

MD
TISSUE

MD NECK
Ligamentous
and
Entheseal
Pain
Points
Patient indicates
the pain zone

Looking for pain

points in the pain zone

Injecting pain
MD
points in the pain
TISSUE
zone
Periosteal pain points

MD
TISSUE

Maigne R. Medicina
manuale. Torino:
UTET, 1996
 “Syndrome segmentaire cellulo-périosto-
myalgique”
R. Maigne
C6 Syndrome
MD
TISSUE
Periosteal pain points
 MD
TISSUE

Dots represent some of

the most common
enthesopathy areas at
the fibroosseous
insertions (Enthesis) in
the occiput, humerus,
trochanter, iliac crest, and
spinous processes.
https://www.scienceofmassage.com/2009/05/science-of-trigger-point-therapy-part-2/
 Pain Points

• Cutaneous

• Ligamentous/Entheseal

• Muscle
 MD MD
MUSCLE TISSUE

Anatomy of the nuchal ligament and trapezius muscle

Anatomy of the nuchal ligament
Injections in the lumbar supraspinous ligament

MD
TISSUE
Injections in the right sacroiliac ligament

MD
TISSUE
 Painful enthesopathies should be
injected in the center of the area of
maximum tenderness and in the
surrounding tender area in a three
dimensional configuration.
Maximum tenderness is usually
encountered at the fibroosseous
junction adjacent to periosteum

Pain Physician. 2005;8:167-173

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PP V
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PA (
)
IA +
Alfieri N. 2016
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PP V
IM X
PA ()
IA +
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toolbox
Collagen MD
Nicola ALFIERI
Physiatrist
Sports Medicine Specialist

nicola.alfieri@gmail.com
www.personasalute.it

Grazie per