NSAIDS and Exercise Induced Muscle Soreness

Weiler J.M. Medical modifiers of sports injury. The use of nonsteroidal
anti-inflammatory drugs (NSAIDs) in sports soft-tissue injury. Clin. Sports
Med.
11(3): 625-644, 1992.
This article provides a background for the use of nonsteroidal anti-inflammatory
drugs (NSAIDs) in sports medicine, including the nature of the drugs, the
settings
and rationale for their use, and concerns about their general safety. The
criteria
for the ideal study to examine the efficacy and safety of NSAIDs after acute
injury
is then enumerated, including a review of how many of the published studies have
met each of the major criteria. Selected studies are described to demonstrate
those
that have or have not provided the basis for a rational decision on the use of
NSAIDs in sports medicine and in the treatment of tendinitis. Finally, this
article
draws conclusions based on these published studies.


MacIntyre D.L., Reid W.D., McKenzie D.C. Delayed muscle soreness. The
inflammatory
response to muscle injury and its clinical implications. Sports Med. 20(1):
24-40,
1995.
Delayed onset muscle soreness (DOMS) is a sensation of discomfort that occurs 1
to
2 days after exercise. The soreness has been reported to be most evident at the
muscle/tendon junction initially, and then spreading throughout the muscle. The
muscle activity which causes the most soreness and injury to the muscle is
eccentric activity. The injury to the muscle has been well described but the
mechanism underlying the injury is not fully understood. Some recent studies
have
focused on the role of the cytoskeleton and its contribution to the sarcomere
injury. Although little has been confirmed regarding the mechanisms involved in
the
production of delayed muscle soreness, it has been suggested that the soreness
may
occur as a result of mechanical factors or it may be biochemical in nature. To
date, there appears to be no relationship between the development of soreness
and
the loss of muscle strength, in that the timing of the two events is different.
Loss of muscle force has been observed immediately after the exercise. However,
by
collecting data at more frequent intervals a second loss of force has been
reported
in mice 1 to 3 days post-exercise. Future studies with humans may find this
second
loss of force to be related to DOMS. The role of inflammation during
exercise-induced muscle injury has not been clearly defined. It is possible that
the inflammatory response may be responsible for initiating, amplifying, and/or
resolving skeletal muscle injury. Evidence from the literature of the
involvement
of cytokines, complement, neutrophils, monocytes and macrophages in the acute
phase
response are presented in this review. Clinically, DOMS is a common but
self-limiting condition that usually requires no treatment. Most exercise
enthusiasts are familiar with its symptoms. However, where a muscle has been
immobilised or debilitated, it is not known how that muscle will respond to
exercise, especially eccentric activity.


Mishra D.K., Friden J., Schmitz M.C., Lieber R.L. Anti-inflammatory medication
after muscle injury. A treatment resulting in short-term improvement but
subsequent
loss of muscle function. J. Bone Joint Surg. 77(10): 1510-1519, 1995.
We studied the effect of flurbiprofen, a non-steroidal anti-inflammatory drug,
on
muscles that had been subjected to exercise-induced injury. The muscles of the
anterior compartment in the limbs of rabbits were cyclically activated as the
ankle
was simultaneously moved through passive plantar flexion every two seconds for
thirty minutes. This treatment imposed acute passive lengthening (eccentric
contractions) of the maximally contracted muscles of the anterior compartment.
After the eccentric contraction-induced muscle injury, one group of rabbits was
treated with oral administration of flurbiprofen, two times a day for six days,
while the other group of rabbits served as untreated controls. The contractile,
histological, and ultrastructural properties of the muscles were measured before
the initial exercise and at three, seven, and twenty-eight days afterward. The
group that was treated with flurbiprofen demonstrated a more complete functional
recovery than the untreated controls at three and seven days but had a deficit
in
torque and force generation at twenty-eight days. The administration of
flurbiprofen also resulted in a dramatic preservation of the intermediate
filament
protein desmin. After three days, the proportion of fibers of the extensor
digitorum longus that lost desmin-staining was significantly greater in the
untreated controls than in the treated animals (34 +/- 4.1 compared with 2.9 +/-
1.7 per cent) (p < 0.001), a finding that supports the concept of a short-term
protective effect. However, the muscles in the treated animals still mounted a
dramatic regenerative response, as indicated by the expression of embryonic
myosin.
Early in the recovery period (at three days), significantly fewer fibers of the
extensor digitorum longus (2.2 +/- 1.4 per cent) expressed embryonic myosin in
the
treated animals than in the untreated controls (11.8 +/- 1.9 per cent) (p <
0.001).
However, at seven days, the expression of embryonic myosin by the muscles from
the
treated animals (19.5 +/- 11.9 per cent) actually exceeded that of the muscles
from
the untreated controls (16.2 +/- 4.1 per cent). This finding suggests either a
delayed or an ineffectual regenerative response by the muscles in the treated
animals.

see related comment:

Swaak A.J. Anti-inflammatory medication after muscle injury. A treatment
resulting
in short-term improvement but subsequent loss of muscle function. J. Bone Joint
Surg. 79(8): 1270-1271, 1997.



Thorsson O., Rantanen J., Hurme T., Kalimo H. Effects of nonsteroidal
antiinflammatory medication on satellite cell proliferation during muscle
regeneration. Am. J. Sports Med. 26(2): 172-176, 1998.
Previous experimental studies have indicated delayed muscle regeneration after
nonsteroidal antiinflammatory drug therapy. Successful regeneration of muscle
after
injury requires activation of normally dormant satellite cells that share the
basal
laminae with adjacent muscle cells. In the presence of adequate capillary
ingrowth,
satellite cells proliferate into myotubes and eventually form new muscle cells.
In
this study, the onset and extent of satellite cell and fibroblast proliferation
as
well as the production of myotubes and capillaries were analyzed with
immunohistochemical methods after contusion injuries to rats' gastrocnemius
muscles. Two groups of animals received daily doses of an intramuscular
nonsteroidal antiinflammatory drug (naproxen) starting 6 hours and 3 days after
injury, respectively. Treated animals were compared with similarly injured
untreated animals. Satellite cell and fibroblast proliferation were unaffected
by
the treatment, and there were no significant differences in myotube or capillary
production between treated and control animals. We conclude that naproxen
treatment
does not compromise the basic process of myofiber regeneration after injury.


Almekinders L.C. Anti-inflammatory treatment of muscular injuries in sport. An
update of recent studies. Sports Med. 28(6): 383-388, 1999.
Stretch-induced muscle injuries or strains, muscle contusions and delayed-onset
muscle soreness (DOMS) are common muscle problems in athletes. Anti-inflammatory
treatment is often used for the pain and disability associated with these
injuries.
The most recent studies on nonsteroidal anti-inflammatory drugs (NSAIDs) in
strains
and contusions suggest that the use of NSAIDs can result in a modest inhibition
of
the initial inflammatory response and its symptoms. However, this may be
associated
with some small negative effects later in the healing phase. Corticosteroids
have
generally been shown to adversely affect the healing of these acute injuries.
Animal studies have suggested that anabolic steroids may actually aid in the
healing process, but clinical studies are not yet available and the exact role
of
these drugs has yet to be determined. Studies on anti-inflammatory treatment of
DOMS have yielded conflicting results. However, the effect of NSAIDs on DOMS
appears small at best. Future research may have to focus on different aspects of
these injuries as the emphasis on anti-inflammatory treatment has yielded
somewhat
disappointing results.


Baldwin A.C., Stevenson S.W., Dudley G.A. Nonsteroidal anti-inflammatory
therapy
after eccentric exercise in healthy older individuals. Journals of Gerontology
Series A: Biol. Sci. Med. Sci. 56(8): M510-M513, 2001.
Aging is associated with greater susceptibility to muscle injury and soreness
after
exercise. Although elderly persons regularly consume nonsteroidal
anti-inflammatory
drugs (NSAIDs), it is not clear that NSAIDs alleviate muscle dysfunction and/or
inflammation following injurious exercise. In this double-blind crossover study,
10
men and 5 women (aged 60 +/- 2 years, mean +/- SE) consumed naproxen sodium or
placebo for 10 days after performing 64 unilateral eccentric (ECC) knee
extensions
using 75% of the ECC 1-repetition maximum. Strength was measured before, 3 days
after, and 10 days after each bout. Injury and soreness were assessed using
magnetic resonance images of m. quadriceps femoris (QF) and a visual analog
scale.
Three days after exercise, concentric strength loss was greater for placebo (-32
+/- 9%) than NSAID (-6 +/- 8%; p =.0064). Likewise, isometric strength declined
less for NSAID than placebo (-12 +/- 7% vs -24 +/- 4%; p =.0213), and thigh
soreness while rising from a chair was greater for placebo (p < or =.0393) than
NSAID (43 +/- 7 mm vs 26 +/- 7 mm). QF cross-sectional area (cm(2)) showing
elevated T(2) was 27% and 35% greater (p < or =.0096) for placebo on Days 3 and
10,
respectively. Naproxen sodium attenuated muscle injury, strength loss, and
soreness
following ECC exercise in older individuals and may be beneficial during the
early
stages of increased physical activity.


Baldwin Lanier A. Use of nonsteroidal anti-inflammatory drugs following
exercise-induced muscle injury. Sports Med. 33(3): 177-186, 2003.
The objective of this article is to examine the use of NSAIDs for attenuating
exercise-induced muscle injuries (EIMI), with an emphasis on their safety and
usefulness for improving muscle function and reducing soreness. NSAIDs are some
of
the most widely consumed medications in the world, and NSAID use as therapy for
EIMI has increased dramatically over the last 20 years. However, there is a lack
of
agreement concerning NSAID effectiveness for this purpose. The lack of consensus
about the efficacy of NSAID use in relation to EIMI has spawned a recent
interest
in sports medicine research regarding NSAIDs.The application of a variety of
methods used to induce, assess and quantify muscle injury has contributed to the
inconsistency among the findings regarding the efficacy of NSAIDs for EIMI.
Therefore, future studies should focus on the evaluation of muscle injury and
function, with the use of better functional measurement tools and more
uniformity
in the assessment tools used. However, from review of the current literature, it
is
concluded that NSAID use for brief periods of time is beneficial for short-term
recovery of muscle function and is an important laboratory tool for the study of
EIMI.