Clinical signs and symptoms of acute reflex sympathetic dystrophy in one hindlimb of the rat, induced by infusion of a free-radical donor.

The acute phase of reflex sympathetic dystrophy (RSD) is characterized by the classical signs and symptoms of inflammation (rubor, calor, dolor, tumor and impaired function). As free radicals are involved in acute inflammation, we studied the effects of free radicals in an animal model, especially as to signs and symptoms found in acute RSD. Awake rats were given continuous intra-arterial infusion (1 ml/h) in the left hindlimb, with saline (n = 6) or the free-radical donor tert-butylhydroperoxide (tert-BuOOH, 25 mM, n = 6). During a 24-h infusion period the skin temperature, volume, skin color, function and pain reactions of the paws were observed. After 24 h the rats were killed and both gastrocnemius muscles were histologically analyzed. Infusion with tert-BuOOH induced in the left paw an increased skin temperature, increased volume, redness of the plantar skin, impaired function and increased pain sensation, while these acute RSD signs and symptoms were absent in the saline infused animals. The alterations in pain sensation (spontaneous, mechanical and thermal pain) were similar to findings in the neuropathic animal model. The gastrocnemius muscles of the saline infused rats and the contralateral gastrocnemius muscle of the tert-BuOOH infused rats showed no histological tissue damage. In the left gastrocnemius muscle free-radical-related damage was visible. Induction of free-radical formation in one hindlimb of awake rats mimics the acute signs and symptoms of acute RSD, with alterations in pain sensation as found in the classical neuropathic animal model of RSD, as well as in acute RSD patients.