0954 - Trocoxil Pre Launch Advertorial_FINAL.
pdf 24/7/09 09:28:00
Pain and the progression of canine OA
A growing body of evidence
suggests that we should re-assess
our management of osteoar-
thritis (OA) if we are to provide
pets with the best possible
long-term prognosis.
In recent years our understanding of joint
pain, and in particular the mechanisms that
drive it, has changed. It is now apparent that
pain is not only a consequence of osteoarthritis,
but may also play a part in driving the disease
process.1
This new understanding has profound implica-
tions for the way we manage dogs with
osteoarthritis. It increases the importance of
minimising or preventing pain. Providing
intermittent NSAID treatment, to treat flare-
ups, may not provide the best long-term
outcome. Instead, continuous NSAID therapy
may be more beneficial.
Sensitization
Research has shown that the components of the
pain pathway can change in response to a
pain stimulus. Pain receptors `up-regulate´ in
response to painful stimuli and become more
sensitive to subsequent pain. As a result,
previously non-painful events (such as touch)
can be interpreted as painful stimuli. Pain
sensitization (`wind-up´) can also result in
hyperalgesia where the pain threshold to
noxious stimuli is lessened, so that mild to
moderate pain is experienced as a more
intense pain. These changes occur in both
peripheral and central pain pathways.2,3
In the central pain pathways, exposure to
repeated painful stimuli changes the way pain is
processed. This so-called `central sensitization´
PAIN
INFLAMMATION
Central
Sensitization
`WIND-UP´
Rate
of cartilage
degradation
Joint
instability
The pain sensitization `wind-up´ cycle
heightens the intensity of pain experienced
following noxious stimuli. This is very important
because the changes are anatomical and
long lasting. Once established, central
sensitization is difficult to control, even with
potent analgesics – so prevention can be the
key to management.
Osteoarthritic pain is harmful in several ways:
A vicious cycle develops whereby repeated
exposure to pain leads to central sensitization
which in turn makes the pain more severe and
difficult to control and further perpetuates
central sensitization.
Dogs with painful OA are reluctant to
exercise. Reduced activity leads to muscle
wasting, which is one of the factors that may
contribute to OA disease progression.4
Central sensitization can increase the level
of inflammation in joints.5 Inflammatory
mediators such as PGE2 have been shown to
contribute to cartilage degradation.6
The role of NSAID therapy
COX-2 enzymes have been shown to play
a role in the development of central
sensitization7, and their inhibition by NSAIDs
can prevent its development.8 Treatment of
central sensitization has been shown to
reduce joint inflammation in models of
arthritis.9
If administration of daily NSAIDs is not
continuous, there is a risk that dogs will suffer
pain which will stimulate pain pathways
resulting in central sensitization.
The message is clear: potentially if pain
can be prevented by continuous
pain management, then the pain
pathways will not be sensitized and
central sensitization will not occur.
Load
Obesity
Inactivity
DISUSE
muscle wasting
For further information please contact Pfizer Animal Health, Walton Oaks, Tadworth, Surrey KT20 7NS POM-V
Reassessing pain management
– Clinical evidence supporting
this theory
A soon-to-be-published systematic review
of all the published studies on long-term
continuous NSAID therapy (daily for 28 days
or longer) in dogs with OA indicated a benefit
of long-term continuous treatment with
NSAIDs over short-term treatment and no
evidence of any increase in side-effects.10
Will owners play their part?
With continuous NSAID therapy owners can
be reassured that their pet is relieved of the
pain and inflammation of OA, allowing
improved joint function and mobility, and
perhaps slower disease progression.
However this approach requires an increased
commitment from the owner. Daily dosing is
undoubtedly inconvenient and at times may
reduce compliance. One answer lies in the
use of a new long-acting NSAID.
Trocoxil™ – the first and
only once-monthly NSAID
Trocoxil (mavacoxib) is a new, innovative
preferential COX-2 inhibitor with a profile
which is ideally suited to continuous
treatment of pain and inflammation
associated with canine OA. After the
second dose, Trocoxil is administered
once a month in the form of flavoured
chewable tablets.
A multicentre study involving client owned
dogs with OA has shown that successive
monthly dosing with Trocoxil leads to contin-
ued improvement.
11
In clinical field studies, the side-effects
seen with Trocoxil have been similar in
type, frequency and duration to those seen
with daily carprofen.
11
References 1. Fiorentino PM et al. Spinal Interleukin-1β in a mouse model of arthritis
and joint pain. Arthritis Rheum 2008. 58(10): 3100-9 2. Hellyer P et al. AAHA/AAFP
Pain Management Guidelines for Dogs & Cats. J Am Anim Hosp Assoc 2007; 43(5):
235-48 3. Schaible HG et al. Pathophysiology and treatment of pain in joint
disease. Adv Drug Deliv Rev 2006; 58(2): 323-42 4. Herzog W et al. The role of
muscles in joint degeneration and osteoarthritis. J Biomech 2007; 40(suppl 1):
S54-63 5. Sluka KA et al. Joint inflammation is reduced by dorsal rhizotomy and not
by sympathectomy or spinal cord transection. Ann Rheum Dis 1994; 53(5): 309-14
6. Hardy MM et al. Cyclooxygenase 2-dependent Prostaglandin E2 modulates
cartilage proteoglycan degradation in human osteoarthritis explants. Arthritis Rheum
2002; 46(7): 1789-803 7. Samad TA et al. Interleukin-1β–mediated induction of
COX-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001;
410(6827): 471-5 8. Veiga AP et al. Prevention by celecoxib of secondary
hyperalgesia induced by formalin in rats. Life Sci 2004; 75(23): 2807-17 9. Sluka
KA et al. Reduction in joint swelling and hyperalgesia following post-treatment with a
non-NMDA glutamate receptor antagonist. Pain 1994; 59(1): 95-100 10. Innes et
al. Systematic review of the safety and efficacy of long term NSAID use in the
treatment in canine osteoarthritis. Vet Record. (In press) 11. Payne-Johnson et al.
Determination of the efficacy and safety of mavacoxib tablets administered monthly
at 2mg/kg bw in the treatment of pain and inflammation associated with
osteoarthritis in dogs. BSAVA abstract 2009.
Trocoxil contains Mavacoxib.
AH314/09