Differential activation of the μ-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model.

Autor: Nakamura, Atsushi, Hasegawa, Minoru, Minami, Kazuhisa, Kanbara, Tomoe, Tomii, Takako, Nishiyori, Atsushi, Narita, Minoru, Suzuki, Tsutomu, Kato, Akira
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Zdroj: British Journal of Pharmacology; Jan2013, Vol. 168 Issue 2, p375-388, 14p, 1 Chart, 7 Graphs
Abstrakt: 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 Bmax of [3 H]- DAMGO binding was reduced by 15-45% in the periaqueductal grey matter ( PAG), region ventral to the PAG (v PAG), mediodorsal thalamus (m TH), 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, v PAG, m TH 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, v PAG and m TH, 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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