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.
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.
Authors: Anna A Birukova; Djanybek Adyshev; Boris Gorshkov; Gary M Bokoch; Konstantin G Birukov; Alexander D Verin Journal: Am J Physiol Lung Cell Mol Physiol Date: 2005-10-28 Impact factor: 5.464
Authors: Kim K Lemberg; Vesa K Kontinen; Antti O Siiskonen; Kaarin M Viljakka; Jari T Yli-Kauhaluoma; Esa R Korpi; Eija A Kalso Journal: Anesthesiology Date: 2006-10 Impact factor: 7.892
Authors: Karine Thibault; Bernard Calvino; Isabelle Rivals; Fabien Marchand; Sophie Dubacq; Stephen B McMahon; Sophie Pezet Journal: PLoS One Date: 2014-03-11 Impact factor: 3.240