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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nishiyori, Atsushi Kato, Akira Hasegawa, Minoru Narita, Minoru Suzuki, Tsutomu Minami, Kazuhisa Tomii, Takako Nakamura, Atsushi Kanbara, Tomoe |
| Description | Author Affiliation: Nakamura A ( Pain & Neurology, Discovery Research Laboratories, Shionogi Co., Ltd, Toyonaka, Osaka, Japan.) |
| Abstract | BACKGROUND AND PURPOSE: Bone cancer pain is chronic and often difficult to control with opioids. However, recent studies have shown that several opioids have distinct analgesic profiles in chronic pain. EXPERIMENTAL APPROACH: To clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the µ-opioid receptor were examined using a mouse femur bone cancer (FBC) model. KEY RESULTS: In the FBC model, the B(max) of [(3) H]-DAMGO binding was reduced by 15-45% in the periaqueductal grey matter (PAG), region ventral to the PAG (vPAG), mediodorsal thalamus (mTH), ventral thalamus and spinal cord. Oxycodone (10(-8) -10(-5) M) and morphine (10(-8) -10(-5) M) activated [(35) S]-GTPγS binding, but the activation was significantly attenuated in the PAG, vPAG, mTH and spinal cord in the FBC model. Interestingly, the attenuation of oxycodone-induced [(35) S]-GTPγS binding was quite limited (9-26%) in comparison with that of morphine (46-65%) in the PAG, vPAG and mTH, but not in the spinal cord. Furthermore, i.c.v. oxycodone at doses of 0.02-1.0 µg per mouse clearly inhibited pain-related behaviours, such as guarding, limb-use abnormalities and allodynia-like behaviour in the FBC model mice, while i.c.v. morphine (0.05-2.0 µg per mouse) had only partial or little analgesic effect on limb-use abnormalities and allodynia-like behaviour. CONCLUSION AND IMPLICATIONS: These results show that µ-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the µ-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 168 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2013-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Analgesics, Opioid Pharmacology Bone Neoplasms Physiopathology Morphine Oxycodone Pain Receptors, Opioid, Mu Physiology Therapeutic Use Animals Behavior, Animal Drug Effects Drug Therapy Metabolism Brain Cell Line, Tumor Disease Models, Animal Guanosine 5'-O-(3-Thiotriphosphate) Mice Mice, Inbred C3H Spinal Cord |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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