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[Treatment of Cancer Pain and Medical Narcotics].

Abstract
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.
AuthorsTsutomu Suzuki
JournalYakugaku zasshi : Journal of the Pharmaceutical Society of Japan (Yakugaku Zasshi) Vol. 135 Issue 12 Pg. 1325-34 ( 2015) ISSN: 1347-5231 [Electronic] Japan
PMID26632147 (Publication Type: English Abstract, Journal Article, Review)
Chemical References
  • Narcotics
Topics
  • Animals
  • Humans
  • Mice
  • Narcotics (administration & dosage, therapeutic use)
  • Neoplasms (complications)
  • Opioid-Related Disorders (prevention & control)
  • Pain (drug therapy)

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