This study determined whether
opiates alter vascular components of
inflammation (
hyperthermia,
edema and plasma extravasation) in addition to the suppression of
hyperalgesia. Rats were administered
carrageenan into one hind paw and saline into the other hind paw, followed by i.p. injection of
morphine (0.2-5.0 mg/kg) or saline at 60 min, and testing at 90 min after hind paw
injections.
Morphine produced a dose-dependent reduction in
carrageenan-induced
hyperalgesia (17-53%),
hyperthermia (39-53%) and
edema (24-36%).
Morphine treatment did not alter the temperatures of the contralateral saline-injected paws, indicating that
opiate suppression of
hyperthermia was not confounded by alterations in systemic body temperature or blood flow. The
opiate effects on
inflammation were stereospecific since
levorphanol (1 mg/kg), but not
dextrorphan (1 mg/kg), suppressed
carrageenan-evoked
hyperalgesia,
hyperthermia and
edema. Pre-treatment with
naltrexone (1.5 mg/kg) blocked the effects of a 5 mg/kg dose of
morphine sulfate on
hyperalgesia,
hyperthermia and
edema. In a separate study, i.v. injection of
morphine sulfate (2 mg/kg) reduced plasma extravasation by 41% (P less than 0.01).
Morphine administration resulted in significantly greater increases in paw withdrawal latencies in the inflamed (38-139%) than the contralateral, saline-treated paws (4-19%). The results indicate that
opiates exert a moderate, though significant, reduction in the vascular signs of
inflammation in addition to their reduction of
hyperalgesia. The mechanisms for this vascular effect involve inhibition of both vasodilation (as indicated by a decrease in
hyperthermia) and inhibition of vascular permeability. In addition,
opiates exhibit enhanced antinociceptive effects in inflamed paws, even when compared to uninjured paws in the same animal.