چكيده لاتين :
It has been shown that stress and chronic pain could prevent the development of tolerance to
morphine analgesia, which appears to be related to the activation of hypothalamus-pitutitaryadrenal
(HPA) axis, activation of neuroendocrine systems and changes in neurochemical levels.
Moreover, the involvement of nitric oxide (NO) in the development of tolerance to morphine
analgesia has been implicated. In the present study, we have tried to investigate the effect of
swim stress, as a painless kind of stress, on the development of tolerance to find out whether the
inhibition of tolerance is mediated by the direct effect ofpain on the pain conduction pathway, or
by its stress aspect. Besides, we evaluated the probable interactions between swim stress, nitric
oxide level and the development of morphine tolerance. Adult male Wistar rats, weighing 180220
g, were used in all these experiments. The experimental groups received chronic morphine
(20 mg/kg, i.p), swim stress in 200e water bath (4 min), or a combination of swim stress and
chronic morphine (20 mg/kg, i.p), each for 4 days, while the first control group received saline
(I ml/kg, i.p) for 4 days. On the 5th day, all the experimental and control groups received a
single dose of morphine (10 mg/kg i.p). The second control group received saline for 5 days.
The intact group received only one single dose of morphine (10 mg/kg, i.p). All the mentioned
groups were subjected to tail-flick and formalin tests on the 5th day. Other experimental groups
were subjected to the assay for measuring nitrite as an indicator ofNO, using the Griess method.
Our results showed that co-administration of swim stress with chronic morphine prevented the
development of morphine tolerance and the level ofNO increased in the presence of swim stress
(p(LESS THAN)0001). The combination of morphine and swim stress significantly decreased NO production
in comparison with the chronic morphine administered group (p(LESS THAN)O.OOl). These data suggest that
the activation of HPA axis and consequently the suppression of (NO) production induced by
chronic morphine, lead to the inhibition of morphine tolerance
