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The Journal of Bone and Joint Surgery, Vol 77, Issue 10 1510-1519, Copyright © 1995 by Journal of Bone and Joint Surgery, Inc
Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function
DK Mishra, J Friden, MC Schmitz and RL Lieber
Department of Orthopaedics, Veterans Administration Medical Center, San Diego, California, USA.
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.
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