Tendons are sturdy bands of connective tissue that function
by connecting muscles to bones. These channel the force created by each
individual muscle to move the bone. Because of this, they must be sufficiently
powerful to endure the force which is conducted through them yet sufficiently
flexible to act as pulleys around bony prominences.
Collagen is a special protein, found in the extracellular
matrix, or ECM, of connective tissue, which provides the tendons with enough
tensile strength to allow them to stretch accordingly without tearing. The collagen
molecules bind together to form a micro fibril, and multiple micro fibrils join
into each other to form a collagen fibre. A group of collagen fibres forms a
fibre bundle, and many fibre bundles joined together are called a tendon
fascicle.
Each fibre bundles and tendon fascicles are enveloped in a
thin layer of loose connective tissue medically referred to as the endotenon.
The endotenon allows the bundles and fascicles to function independently of one
another, sliding against one another according to each movement in order to
properly adjust to the force and angle between the activity of the muscles and
bones. The endotenon is also an addition of the connective tissue that encloses
the entire tendon, called the epitenon. Some tendons have a supplementary
sheath-like covering called the peratenon, which may function similarly
alongside a tendon but it’s a distinct structure.
Within the tendon, there is a cell called the tenocyte that
regulates and balances the secretion of the extracellular matrix and the
accumulation of the collagen within the tendon. Tenocytes can be found in long
rows along the collagen fibres and can also form in the endotenon and epitenon
of the tendon. The tenocytes arrange into a connective web of finger-like
extensions which allow the cells to communicate with each other according to
the required needs for synthesis or degradation of collagen fibres.
These trigger the development of more collagen cells when
they undergo stresses for short periods of time. However, tension for extended
periods of time can cause collagen inhibition where the blood supply to tendons
is considerably less than that of the muscle to which they are attached. The
vessels that do exist within the tendon are particularly small,
and run alongside the fascicles within the endotenon coat.
Some areas of tendon lack a blood supply altogether. If such occurs, these
areas can be especially vulnerable to degeneration and rupture.
Tendon Injuries
Athletes who frequently overuse their muscles or as a result
of direct trauma can develop tendon injuries. Of the 32 million musculoskeletal
injuries documented in the United States annually, 45% of them are injuries to
tendons, ligaments, or joint capsules. The most commonly injured tendons include
the tendons of the rotator cuff of the shoulder, the Achilles tendon, patellar
tendon, and the elbow extensor tendon. Several factors can place additional
strain on the tendon and contribute to injuries caused by overuse, including: abnormal
direction of pull due to skeletal misalignment; differences in limb lengths; muscle
weakness or imbalances; hypermobile joints;
inflexible muscles;
training
errors; and faulty or improperly fitted equipment and/or footwear.
Tendon injuries are believed to be difficult to treat as
they were once historically thought of as an inflammatory condition, referred
before to as tendonitis. Its treatment was therefore focused on reducing the
inflammation through traditional anti-inflammatory medications and modalities
and was extensively unsuccessful. Further research then demonstrated that acute
inflammatory cells were missing, despite a disruption to the collagen
composition within the injured tendon. A new term, tendinosis, was proclaimed
to describe the degenerative injuries observed in the tendon tissue and the
absence of inflammation. Regardless of the new classification and the inclusion
of innovative therapies to address the degeneration of the tendon rather than
the inflammation, successful treatment of tendon dysfunction, otherwise known
as tendinopathy, has remained ambiguous.
The Significance of Inflammation
Medical advances now allow researchers to take a closer look
at the process of tendinopathy. Studies of injured human tendon are difficult
because by the time a person seeks medical help the injury is generally
considered chronic. Therefore, animal models were studied to reveal acute
tendon changes. Researchers from Queen Mary University in London evaluated the
response of the tenocytes of horse tendons to cyclic loading. Fascicle bundles
from six horses were divided into treatment and control groups for the study.
Then, treatment samples sustained repeated loading strain, while controls
remained unloaded.
After a 24-hour cyclic loading protocol, the collagen cells
within the fascicles of the treated tendons appeared rounded and unorganized,
meanwhile the control collagen cells were long, thin, and aligned
longitudinally along the fascicle. Indications of inflammation were found in
the treated samples after their loading cycle, while the control samples displayed
only a few if any indications of inflammation. The scientists of the study
ultimately concluded that tendon cells respond to increased levels of stress
with an inflammatory reaction, especially in the acute period following injury.
These findings correspond with other animal studies which have
found an increase in inflammatory indications after multiple circumstances of tendon
damage as well as an increase in the number and size of the tenocytes. The increased
production of tenocytes is known to occur in the presence of inflammation;
therefore, this reaction believed to reveal a prior surge of inflammation. While
degeneration has been diagnosed in chronic tendon injury, inflammation may cause
those changes within the tendon during the acute period of tendon injury.
Further Evidence
Once the injured tendons were examined with ultrasound, there
appeared to be an increase in blood flow to the tendons. Healthy tendons are
characteristically lacking in blood supply, therefore, to achieve this
increased circulation, new blood vessels must penetrate the tendon. Known as neovascularization,
this process generally occurs in conjunction within a nerve alongside the blood
vessel. The development of new nerves within the injured tendon is thought to
be the source of pain in tendinopathy.
The increase of blood flow is assumed to be evidence of
degeneration within the tendon and an effort at healing the damaged tissue.
Such neovascularization and neo innervation could likely not occur without the
presence of inflammation. Researchers at Cambridge University show that the
appearance of tendinopathy due to overload or injury can be characterized on
ultrasound apart from those patients with known inflammatory conditions such as
rheumatoid arthritis.
Biochemical Influences
The enzyme cyclooxygenase-2,
or COX-2, which in the presence of arachidonic acid, stimulates the production of
prostanoids and produces inflammation. Studies show that levels of prostanoids
are increased in animal tendons subjected to repeated loading. In tendons
administered with injected prostanoids, the changes recorded within the tendon
are consistent with tendinopathy. Therefore, the presence of greater levels of
prostanoids in injured tendons can be ruled as clear evidence of an
inflammatory process within the tendon.
Substance P is a peptide secreted by nerves and inflammatory
cells. The presence of substance P in considerable amounts in chronic
tendinopathy is thought to be the result of an inflammatory process within the
tendon. Substance P causes an increase in the number of tenocytes within a
tendon. As a result, the increased number of tenocytes discovered in an injured
tendon may be the result of inflammatory mediators such as substance P. Substance
P also increases the amount of collagen III to collagen I molecules in the
extracellular matrix, or ECM. Within a healthy tendon, collagen I is the prevalent
type found within the ECM. This change in the balance of the collagen may well explain
the difference in the shape and size of the collagen and simultaneous disorganization
observed in a study conducted in London.
Degeneration Theory
Scientists in Melbourne, Australia, developed a multi-stage
model of tendon injury that surrounds the current thinking on tendinosis. When
a healthy tendon experiences increased amounts of weight, it responds by
increasing its stiffness to handle the greater force demand and increases the
production of collagen cells. The Australian researchers suggested that this non-inflammatory
cell response, is a reactive tendinopathy. Their thought is that the increase
in cells is an attempt by the tendon to increase the cross-sectional area and therefore,
better handle the increased force on it. This short-term adaptation can be unpredictable
if the added load is gradually decreased or the tendon has a chance to rest
before the next amount of increased pressure is applied. A healthy tendon may
easily adapt to the stress by growing larger and thus stronger, but a damaged
or injured tendon does not recover from the stress and progresses to stage two.
In the second stage, identified as tendon disrepair, the
tendon attempts to heal itself by adding more cells to the ECM, increasing the
protein production of proteoglycans and collagen. It’s believed that these
alter the composition and appearance of the collagen and gives the ECM a more disorganized
appearance. According to the scientists, the composition of the ECM can be
altered and healing may still take place at this stage.
The final stage is medically referred to as degenerative
tendinopathy. The indication of this stage is cell death, with areas of tendon
completely lacking healthy cells and an ECM filled with vessels and metabolic
by-products, among several other things. This stage is considered irreversible.
Degenerative tendinopathy is found as distinct lesions within a tendon. The
injured tendon may display various stages of degeneration throughout the
tendon.
Chiropractic and Athletic Performance
Similar Effects
Previous research reveals that inflammatory alterations and
degenerative alterations are both found within the same tendon. A group of
researchers from Italy and Sweden suggested a different model for tendinopathy,
around both the inflammatory and degenerative observations. Termed the “iceberg
theory”, this model begins with the assumption that normal exercise may
stimulate the production of new collagen within a tendon. Simultaneously,
collagen degradation also occurs, most probably to reconstruct the tendon in
order to accommodate the new amount of stress and pressure. Therefore, exercise
stimulates the production of inflammation and growth substances, both which are
needed for stimulating a healthy tendon. In healthy tendons, the tendon becomes
larger and stronger.
When a tendon experiences constant strain or overload, the
collagen fibres within the tendon begin to shift past one another, breaking
their connective bonds. This micro-trauma is believed to weaken the tendon, and
affects both the ECM and the blood supply. Vigorous or repeated exercise also
increases the temperature within the tendon tissue. Decreasing the buildup of
heat is difficult in tendons. The scientists theorize that it may be the
hyperthermia within the tendon that causes the degeneration of cells rather
than hypoxia.
Stopping any activity where weight is added to the region of
the affected tendon, plenty of rest and adequate blood supply are needed for
the tendon to heal from excessive strain. If the tendon does not have the
required blood supply, factors are produced which stimulate angiogenesis. The
appearance of new vessels, which typically include nerves alongside the blood
vessels, is hypothesized to weaken the structure of the tendon. The secretion
of both glutamate and substance P by the creation of nerves can contribute to a
neurogenic inflammation as well as tendon cell death. It is at this point in
the continuum, that athletes may complain of pain and seek medical attention.
Clinical Relevance
Understanding that there may be both inflammation and
degeneration involved in chronic tendinopathy may improve treatment outcomes.
Since inflammation occurs early in the course of tendinopathy, non-steroidal
anti-inflammatory drugs, or NSAIDS, and steroid injections may be most
effective at the onset of pain or when the athlete suffers strain of the
tendon. Sclerosing therapy and eccentric exercise both function to eliminate or
reduce the number of new blood vessels and nerves in the tendon. By reducing
the amount of new vessels, the tendon can return to normal and while reducing symptoms
of pain. Eccentric exercise has an additional benefit of stimulating collagen
production. Manual therapies, such as augmented soft tissue mobilization, are
thought to also stimulate collagen production and return the ratio of type III
collagen to type I collagen within the ECM to normal.
This new standard of tendon injuries and conditions creates
new ideas for treatments. Treatments currently under investigation include
biologic therapy, nitrous oxide, biochemical scaffolding, exogenous growth
factor, platelet rich plasma injection, stem cell injection, and tissue
engineering. Further research is needed to isolate which tendons and in what
stage of injury, respond best to which therapy. In the meantime, the best
recommendation is to treat any tendinopathy early when the anti-inflammatory
methods are most effective and the chance for healing is greatest.
By Dr. Alex Jimenez