1) Tendinopathy refers to non-inflammatory tendon damage and dysfunction. It is characterized by tendon pain and swelling that is worsened with activity. 2) Multiple factors can contribute to tendinopathy, including mechanical overload, vascular insufficiency, and neural involvement. 3) Current treatment approaches include eccentric exercises, shockwave therapy, laser therapy, prolotherapy, and stem cell therapy, which aim to reduce pain and promote tendon healing.

1. Current Concepts in
Tendinopathies
BY
PALAS PRAMANICK
MPT SPORTS PHYSIOTHERAPY – 2ND
YEAR

2. What is Tendon ?

3. . Tendons are dense connective tissue
structures that connect muscle to bone.
. These are located in and around the joints of
the body, and as a result, they are subjected to
large distractive or tensile loads.
. These structures are largely responsible for
providing movement and function.

4. Physiology of Tendon

5. Hierarchical structure of Tendon

6. Structure of a Tendon
. All body tendons have a similar histological organization, that is, a soft tissue structure
mainly composed by connective cells. This connective tissue includes an extracellular
matrix (ECM) described as a macromolecular network with structural and changing
functions.
. Tendon has a hierarchical structure, well-observed in the ECM, which is high organized
with collagen molecules connecting into filamentous collagen fibrils. These groups of
fibrils are known as collagen fibers, the main structural element of the tendon. Fibrils are
ordered in fibrils packs, fascicles and fiber packs that are aligned in the same direction to
the axis of the tendon, named primary, secondary and tertiary bundles.
. The ECM is composed of parallel collagen fibers that can be further divided into
fascicles, fibrils, subfibrils, microfibrils, and tropocollagen components. Collectively, the
bundled fibers are surrounded by connective tissue layers – epitenon and endotenon –
that allow for frictionless movement and supply blood vessels, nerves, and lymphatics to
deeper tendon structures. Regulation of this highly organized structure by tenocytes,
tenoblasts, and tendon stem progenitor cells (TSPCs) is crucial to maintain proper
mechanical properties and prevent injury.

7. Ultrastructure features of ECM in
Tendon (Type I Collagen) fibrils
Type I Collagen fibrils are in
contact to thin fibrils of
Collagen V

8. Tenoblasts Cells
Tenocytes & Tendon
Stem Progenitor Cells

9. Ultrastructure features of Epitenon

10. Biomechanics of the Tendon
. These structures achieve a mechanical advantage, increasing the force generated by the
muscle by the pulley or lengthening systems. In addition, viscoelastic material properties
allows to maintain and release energy, which is a main mechanism for injury prevention.
. At the first loading stages, tendons suffer an initial stiffness expansion directly
proportional to the received load. Tendon biomechanics, due to this nonlinear
characteristic shows two separate zone in the load- elongation curve.
. It shows the behavior of tendon tissue in response to load activity. On the left side of the
curve, when the load is starting, a low deformation can be ob-served in the stress-strain
curve. After that, there is a cut point where a load increase providing greater tissue
deformity.
. As deformation increases, there is a second cut point where tendon experience
irreversible injury and, if sustained, could suffer a tear or rupture.

11. Load-elongation curve

12. What is Tendinopathy ?

13. . Tendinopathy is a clinical syndrome, often but not always implying
overuse tendon injuries, characterized by a combination of pain, diffuse or
localized swelling and impaired performance.
. Tendinopathy can also occur without signs of overuse, and is then mostly
associated with medical conditions.
. Midportion and insertional tendinopathy (enthesopathy) should be
distinguished as two different clinical diagnoses.
. The tendons most vulnerable to overuse in lower extremities are the
Achilles and patellar tendons and in the upper extremities, the rotator cuff
and extensor carpi radialis brevis (tennis elbow) tendons.

14. Pathophysiology

15. . Maffuli et al. were considered one of the first researchers to
promote a change in the clinical terminology from tendinitis to
tendinopathy.
. Currently, tendinopathy is an accepted term which is used to
indicated a variety of tissue conditions that appear in injured tendons
and describes a non-rupture damage in the tendon or para-tendon,
which is intensified with mechanical loading.
. This shift in the nomenclature has been related with new advances
in the understanding of tendon pathophysiology, implying:
1. Further description of the overuse cycle and the following
structural and functional damage in tendons with chronic pain
2. Increased knowledge about the biomechanical disturbances
which provoke chronic tendon pathology
3. A better picture about the importance of intrinsic and extrinsic
factors related to lifestyle.

16. Phases of Tendinopathy

17. Phase 1
. Reactive tendinopathy is the result of an acute compressive and/or tensile load
which provokes a non-inflammatory proliferative cell and matrix response. This
situation occurs after an acute overload such as an excessive physical activity
periods.
. It is noticed that damaged tendons suffered structural changes observed through
ultrasound.
. Nowadays, some studies show that this adaptive response can be explain as an
effort to maintain an available amount of aligned fibrillar structured to avoid
overloading in the damaged area.
. This enlargement of the tendon surface can decrease stress and increase
stiffness. If there is enough time between loads or the overload is reverted, the
tendon structure can return to normal.

18. Phase 2
. Second phase is defined as tendon disrepair, which
is determined for the development of fibrillar
disorganization.
. This phase is observed as the attempt at tendon
healing, also known before as “failed healing”.
. Changes in the matrix level are more noticeable and
could be caused by an increase of the vascularization
of the tendon due to neuronal maturity.

19. Phase 3
. The last stage is known as degenerative tendinopathy.
. In this phase, a variety of changes can be observed within the matrix
and cells.
. During this period, the possibility of natural recovery decreases.
. Several areas of cells will die related to trauma or tenocyte
apoptosis.
. As a result, large zones of acellularity can be observed and the
disordered zones of the matrix will appear filled with vessels.

21. Aetiology of Tendinopathy
The Mechanical Theory :
. Related to mechanical overload of tendon
. Damage to collagen or other matrix components can accumulate with
repeated stretching, even within physiological limit
. Explains degenerative nature of tendon histology
. Consistent with observation, cumulative damage can lead to ‘spontaneous’
tendon rupture
. Makes sense physiologically
. Does not explain why exercise can improve diseased tendon
. Does not explain why certain tendons are more susceptible than others
. Does not explain spontaneous rupture in patients with lack of exercise
history

22. The Vascular Theory
. States that tendons heal poorly because they, or at least certain parts
of a tendon, have a poor blood supply. They are thus prone to vascular
insufficiency.
. May explain why tendons have vulnerable sections (e.g. mid portion
of Achilles)
. Does not explain why exercise (eccentric loading) can heal tendon
. No convincing evidence of vascular compromise in healthy
individuals
. Role of neovascularization unclear

23. The Neural Theory
. Possible neural aetiology for tendinopathy has been explored. This has been based on a
number of separate observations:
(i) The fact that tendons are innervated
(ii) The close association within tendons of nerve cell endings and mast cells. This raises
the possibility of neurally mediated mast cell degranulation and release of mediators
such as substance P (a nociceptive neurotransmitter) and calcitonin gene related
peptide.
(iii) That increased levels of substance P have been found in rotator cuff tendinopathy
(iv) The fact that substance P has been implicated as a pro-inflammatory mediator
(v) The finding of glutamate, a neurotransmitter, within the ultra-dialysate in Achilles
tendinopathy
(vi) An association between radiculopathy and tendon disorders. Maffulli et al. found an
association between Achilles tendinopathy requiring surgery and sciatica in a
study using peer-nominated controls.

24. Overview of Tendon Injury
. There are many mechanisms of injury that lead to tendinopathy or
tendon rupture, and the injury can be due to a combination of both
acute and chronic trauma.
. Intrinsic factors - Common intrinsic factors that can influence
tendon pathology include :
• Age,
• Gender,
• Biomechanics
• The presence or absence of systemic diseases either inherited (such as
Marfan’s or Ehlers–Danlos syndromes) or acquired (such as
rheumatoid arthritis or diabetes mellitus).

25. . Extrinsic factors - Common extrinsic factors include :
• Physical load on a tendon (load and frequency),
• The environment (e.g. equipment, the working environment,
footwear) and occupation.
• Training error (a rapid, not gradual, increase in workload that does not
allow any adaptation of the tendon over time)
● Genetic factors : It has been reported in some studies that there
is an increased incidence of blood group O in patients with tendon
injuries, particularly Achilles tendon injuries. These results suggest a
genetic linkage between the ABO blood group and the molecular
structure of tendons.
Indeed recent studies have revealed the alpha 1 type V collagen
(COL5A1) gene, which encodes for a structural protein found in
tendons, and the guanine–thymine dinucleotide repeat polymorphism
within the tenascin-C gene, are both associated with chronic Achilles
tendinopathy.

27. A specimen from a patient with chronic patellar tendinopathy
showing collagen fibril separation and frank discontinuity (arrows)
within some fibrils

28. Clinical presentations of
Tendinopathies
. Pain some time after exercise or, more frequently, the following morning upon
rising.
. It can be pain free at rest and initially becomes more painful with use.
. Athletes can "run through" the pain or the pain disappears when they warm up,
only to return after exercise when they cool down.
. The athlete is able to continue to train fully in the early stages of the condition;
this may interfere with the healing process.
. Examination reveals local tenderness and/or thickening on palpation (primary
hyperalgesia).
. Frank swelling and crepitus may be present, although crepitus is more usually
a sign of associated tenosynovitis (it is not-inflammatory fluid").

29. Tendon-healing
Physiology

30. 1. Inflammation (Days) :
. Formation of hematoma
. Invasion of cells for phagocytosis (Neutrophils, macrophages )
. Release of pro-inflammatory cytokines
. Molecular mediators : 1. IGF1 - Stimulation of proliferation and migration
2. TGFβ - Stimulates collagen production and cell
migration, regulates proteinases.
3. PDGF - Stimulates DNA and protein synthesis
2. Proliferation (Weeks) :
. Deposition of randomly organized proteoglycans and collagen
. Increased cellularity (Fibroblasts increase type III collagen )
. Activation of TSPCs

31. . Molecular mediators :
1. IGF1 - Stimulation of proliferation and migration
2. TGFβ - Stimulates collagen production and cell migration, regulates
proteinases
3. PDGF - Stimulates DNA and protein synthesis
4. FGF2 - Regulates angiogenesis and cellular migration
5. VEGF - Promote neovascularization
6. BMPs - Regulate differentiation of stem cells
3. Remodeling (Months–years) :
. Decrease in cellularity and matrix production
. Transition from type III to type I collagen (Fibroblasts regulate type III –I
collagen transition)
. Increase collagen-fiber cross-linking

32. Molecular mediators :
1. IGF1 - Stimulation of proliferation and migration
2. TGFβ - Stimulates collagen production and cell
migration, regulates proteinases
3. FGF2 - Regulates angiogenesis and cellular
migration
4. VEGF - Promotes neovascularization
5. MMPs - Collagen degradation and reorganization

33. Current Trends
in the Management
of
Tendinopathies

34. 1. Gene Therapy Approaches
. Matrix molecules (tenomodulin - Tnmd, periostin) (Jiang et al.
2016, Noack et al. 2014).
. Growth factors (platelet-derived growth factor B - PDGF-B,
vascular endothelial growth factor - VEGF, basic fibroblast
growth factor - FGF-2, growth and differentiation factor 5 -
GDF-5, insulin-like growth factor I - IGF-I, TGF-βeta, bone
morphogenetic protein 12 - BMP-12) (Basile et al. 2008, Cai et al.
2013, Hasslund et al. 2014, Lou et al. 2001, Majewski et al. 2008,
2012, Nakamura et al. 1998, Rickert et al. 2005, Schnabel et al.
2009, Tang et al. 2008, 2014, 2016, Wang et al., 2004, 2005, 2007).
. Anti-inflammatory molecules (peroxiredoxin - PRDX5) (Yuan et
al. 2004) and chemokines (CXC chemokine ligand 13 - CXCL13)
(Tian et al. 2015).

35. 2. “ P E A C E ” & “ L O V E ”
P (Protection) – avoid activities & movements that increase the pain from the day of
injury
E (Elevation) - Elevate the limb higher than the heart as possible
A (Avoid Anti-Inflammatories) – They reduce tissue healing
C (Compression) – Use elastic adhesive bandage to reduce swelling
E (Education) – Avoid unnecessary passive treatments medical investigations
&
L (Load) - Let play guide your gradual return to normal activities & to increase the load
O (Optimism) – Condition your body for optimal recovery by being positive & confident
V (Vascularization) – Choose pain free cardiovascular activities to increase blood flow for
healing
E (Exercise) - Restore mobility, strength by adopting active approach to recovery

36. 3. Eccentric exercises
. Eccentric exercises have been proposed to promote collagen fiber
cross-link formation within the tendon, thereby facilitating tendon
remodeling.
. The basic principles in an eccentric loading regime are length of
tendon, load, and speed. If the tendon is pre-stretched, its resting length
is increased, and there will be less strain on that tendon during
movement.
. By progressively increasing the load exerted on the tendon, there
should be a resultant increase in the inherent strength of the tendon
itself.
. By increasing the speed of contraction, greater force will be developed.

37. Eccentric loading of the right gastrocnemius muscle/Achilles tendon showing the
starting position (A) and finishing position (B). Three sets of 15 repetitions are
performed twice per day, 7 days per week for 12 weeks.
A B

38. Typical appearance of a hypoechoic Achilles
tendon prior to commencing an eccentric
loading programme.
The appearance after a long-term eccentric
loading programme. Loss of hypoechoic
appearance and reduced tendon thickening are
demonstrated.
Ultrasound appearance of Achilles tendon before and after a long
term eccentric loading programme

39. 4. Extracorporeal shock wave
therapy
. Extracorporeal SWT is a noninvasive procedure which uses single pulsed acoustic
or sonic waves generated outside the body and focused at a specific site within the
body.
. Low-energy SWT in tendinopathy has been proposed to stimulate soft tissue healing
and inhibit pain receptors.
. Experimentally, low-energy SWT stimulates soft tissue healing and inhibits pain
receptors. Effects after repetitive application were significantly greater than after
single application.
. Combining eccentric training and shock wave therapy (SWT) produces higher
success rates compared with eccentric loading alone or SWT alone.

40. 5. Low-energy Laser Therapy
. Low-level Laser Therapy (LLLT) has the ability to reduce
inflammation and stimulate collagen production.
. The anti-inflammatory effect of LLLT in humans has been analyzed
through microdialysis, a minimally invasive sampling technique that
provides continuous measurement of peritendinous fluid.
. As more studies emerge that effectively demonstrate the validity of
LLLT as a therapy for injury repair and investigate ideal application
methods, LLLT has the potential to become more widely accepted for
clinical use.

41. 6. Regenerative Injection Therapy
(Prolotherapy)
. Regenerative injection therapy (prolotherapy) is the injection of growth factors or growth factor production
stimulants to promote the regeneration of normal cells and tissue. Inflammation is not required, and scarring is
not the result.
. Conditions that are critically blocking full performance in the athlete and that are not amenable to surgery or
that would require long periods of sports cessation are suitable for consecutive patient study using
noninflammatory or inflammatory proliferant solutions.
. An example is a study by Topol and colleagues of 24 consecutive elite athletes (22 rugby and 2 soccer)
with career threatening or, potentially, career-ending chronic groin pain preventing full sports
participation that was nonresponsive to therapy with graded sports reintroduction.23 Patients received
monthly injection of 12.5% dextrose and 0.5% lidocaine in adductor and abdominal insertions and the
symphysis pubis, depending on palpation tenderness. Injections were given until complete resolution or
lack of improvement for two consecutive treatments occurred. A mean of 2.8 treatments were given. A
reduction in the visual analog pain scale score for pain with sports was from a mean of 6.3 to 1.0 (P <
0.0001), and the reduction in the Nirschl pain phase scale score was from 5.25 to 0.79 (P < 0.0001).
Twenty out of 24 patients had no pain in the groin at an average follow-up time of 17 months, and 22
out of 24 patients were no longer restricted with regard to sports participation, with a success rate of
return to elite sports of 92% (LOE: D).

42. 7. Surgeries
1. Radiofrequency microtenotomy : Safe and effective
procedure to manage patients with chronic tendinopathy.
Early degeneration followed by later regeneration of nerve
fibers after bipolar radiofrequency treatment may explain
long-term postoperative pain relief after microtenotomy for
tendinopathy.
2. Neovessel destruction : These procedures are
intrinsically different from the classical ones in present use,
because they do not attempt to directly address the
pathologic lesion, but act only to denervate them.

43. Existing Treatments
1. Cryotherapy : Cryotherapy is believed to reduce blood flow and tendon metabolic
rate and hence swelling and inflammation in an acute injury.
2. Therapeutic ultrasound : Therapeutic ultrasound is a common physical treatment for
tendon disorders. Ultrasound has a thermal effect on tissues, causing local heating,
although this may be attenuated by the use of a pulsed (intermittent) process.
3. Manual therapy techniques : A popular technique is of soft tissue mobilization.
Mobilization via massage of the area around an injured tendon will stimulate blood supply
in the vicinity of the injury and this is thought to promote healing of the affected tendon.

44. Thank You