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Pointing light at musculoskeletal and neurological conditions: clinical applications 117

degeneration, osteoarthritis is a progressive inflam- how LT can decrease the expression of certain medi-
matory and degenerative disease that involves several ators, such as IL-1 and TNF. Among the enzymes, the

structures and tissues. The articular cartilage degener- most important are matrix metalloproteinases (MMPs),
ates and is progressively lost, the bones undergo hyper- which are released by chondrocytes, synoviocytes,

trophic changes, there is inflammation and fibrosis of and inflammatory cells, contributing to cartilage deg-

the synovial membrane and periarticular structures, radation. Although some MMPs have physiological

as well as qualitative and quantitative changes in syno- functions, others increase during inflammation (and

vial fluid. Nearby ligament attachments are eventually cancer), serve as biomarkers, and are related to the
affected too, and the patient suffers pain and loss of severity of cartilage damage.

functionality. About 20% of dogs that are older than 1 Different etiologies may present different profiles

year suffer from OA and this percentage increases to of mediators – they all have inflammatory soups but

80% if we consider dogs over 8 years. [311, 312] It is the the amounts of the ingredients may vary. For instance,
most common source of pain and loss of mobility in MMP-1, MMP-2, and MMP-9 are clearly increased in
older dogs. The impact on our feline patients is often dogs with OA, [320–322] although some MMP-2 activity

underestimated; although there is no direct correlation can be detected at lower levels in healthy joints. [323]
between radiographic signs and pain, a study in 100 cli- Canine immune-mediated arthritis displays an even
ent-owned cats over 6 years of age found radiographic higher increase in IL-1 and TNF than OA, [324] which
evidence of appendicular OA in more than 60% of correlates with the amount of MMP-3, also elevated
them. [313] Another report increased this number to over in the synovial fluid of dogs with rheumatoid arthri-

90%, [314] with an increase of 13.6% in expected total DJD tis when compared to OA patients. [325] Unfortunately,
score for each 1-year increase in the age of the cat. OA these biomarkers are not yet used in practice due to
also has a huge financial impact; it is the most common the lack of molecular diagnostic tests. Hopefully in the

reason to prescribe non-steroidal anti-inflammatory future these will be available to improve diagnosis and
drugs (NSAIDs), which represents a market of over 400 monitoring of the disease. [326]

million USD per year, [315, 316] with millions of pets being The reason I’m kind of torturing you with the molec-
treated every year. [317] ular basis of articular inflammation is because LT has

A lot has been written about OA treatment, and it is consistently been reported to act at this level. Acute
very clear that its management has to be multimodal. joint inflammation decreases with LT due to the reduc-

There is no such thing as a cure: the focus is on con- tion in the pro-inflammatory mediators IL-1, COX-2,
trolling the painful and limiting consequences and TNF, and IL-6. [37, 41, 78, 296, 327–329] LT can also reduce the

trying to slow down cartilage degradation, using phar- inflammatory infiltrate; in osteoarthritis models, for

macological analgesia, physical modalities, and nutra- instance, it decreases polymorphonuclear cells in the

ceuticals. And we can’t forget weight control, a MUST synovial fluid and capsule. [41, 73] The resolution of the

with or without laser: diet restriction clearly delays the inflammation is further enhanced with the production
onset and decreases the severity of OA. [318] Weight of substances such as TGF-β, both in healthy and exper-
reduction by itself can reduce clinical signs of lameness imentally-induced diabetic models. [330] Besides, LT can
in dogs with osteoarthritis. [319] decrease the above-mentioned MMP levels to inhibit

Other forms of arthritis we may find in small animal cartilage degradation – specifically MMP-2, MMP-3,
practice include septic and traumatic etiologies, rheu- MMP-9, and MMP-13. [8, 78, 295, 296, 331, 332]
matoid arthritis, or those related to systemic infections More recently, the role of nerve growth factor (NGF)

that lead to arthritic pain, including Leishmania and in joint inflammation and cartilage degradation and its
Rickettsia, among others. But all forms of arthritis share use as a therapeutic target has been described with very
the fact that the levels of pro-inflammatory mediators promising results. [333, 334] The effect of LT on this par-

are increased and this changes the metabolism of chon- ticular mechanism should be investigated, since some
drocytes and other cells. studies suggest LT could promote NGF release, [89]

Three groups of canine synovial fluid biomarkers which would theoretically enhance inflammation. But

have been investigated: pro-inflammatory mediators, after reading Chapter 3, you know that the course of
enzymes and their inhibitors, and extracellular cartilage inflammation definitely does not depend on just one

degeneration products. We have previously discussed ingredient.
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