The World Health Organization has reported that when
morphine is used to control
pain in
cancer patients, psychological dependence is not a major concern. Our studies were undertaken to ascertain the modulation of psychological dependence on
morphine under a
chronic pain-like state in rats.
Morphine induced a dose-dependent place preference. We found that inflammatory and
neuropathic pain-like states significantly suppressed the
morphine-induced rewarding effect. In an inflammatory
pain-like state, the suppressive effect was significantly recovered by treatment with a κ-
opioid receptor antagonist. In addition, in vivo microdialysis studies clearly showed that the
morphine-induced increase in the extracellular levels of
dopamine (DA) in the nucleus accumbens (N.Acc.) was significantly decreased in rats pretreated with
formalin. This effect was in turn reversed by the microinjection of a specific
dynorphin A antibody into the N.Acc. These findings suggest that the inflammatory
pain-like state may have caused the sustained activation of the κ-opioidergic system within the N.Acc., resulting in suppression of the
morphine-induced rewarding effect in rats. On the other hand, we found that attenuation of the
morphine-induced place preference under
neuropathic pain may result from a decrease in the
morphine-induced DA release in the N.Acc with a reduction in the μ-
opioid receptor-mediated
G-protein activation in the ventral tegmental area (VTA). Moreover, nerve injury results in the continuous release of endogenous β-
endorphin to cause the dysfunction of μ-
opioid receptors in the VTA. This paper also provides a review to clarify misunderstandings of
opioid analgesic use to control
pain in
cancer patients.