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

Abstract

BACKGROUND AND PURPOSEBone 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 APPROACHTo clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the m-opioid receptor were examined using a mouse femur bone cancer (FBC) model. KEY RESULTSIn the FBC model, the Bmax of [ CONCLUSION AND IMPLICATIONSThese results show that m-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the m-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine.

Effect of the Norepinephrine Transporter (NET) Inhibition on μ-Opioid Receptor (MOR)-Induced Anti-nociception in a Bone Cancer Pain Model

“…Compared with sham controls, we have determined previously that the expression of MORs on the cell membrane in the FBC model was reduced by approximately 30%, determined by B max of 3 H DAMGO binding, without affecting the K d in pain-related regions (32). In addition, it has been reported that the agonist activity of partial agonists was reduced more by a change in the number of receptors compared to that of full agonists (33,34).…”

Morphine and oxycodone, but not fentanyl, exhibit antinociceptive effects mediated by G-protein inwardly rectifying potassium (GIRK) channels in an oxaliplatin-induced neuropathy rat model

“…Because we had previously validated the optimal dose and preinjection time of tertiapin-Q [9], in the present study we used tertiapin-Q at 30 pmol 10 min before opioid administration. The anitnociceptive effects of MOR agonists were assessed 15 min after administration of oxycodone and fentanyl or 30 min after morphine administration, respectively, because these MOR agonists exhibited peak antinociception at these time points [4,5,17]. As with our previous report [13], chronic oxaliplatin treatment significantly decreased paw withdrawal thresholds, and morphine (3 mg/kg, s.c.) and oxycodone (0.56 mg/kg, s.c.) reversed the decreased paw withdrawal thresholds with maximum paw withdrawal thresholds equipotent to the sham groups while fentanyl (0.017 mg/kg, s.c.) partially reversed the attenuated paw withdrawal threshold (Fig.…”

“…Although these MOR agonists show potent analgesic effects against various types of pain [1,2], they have different analgesic profiles in clinical settings [3]. Consistent with this, MOR agonists have interesting antinociceptive differences in several pain model rodents [4][5][6]. Therefore, it is important to understand pharmacological profiles of those for the appropriate use.…”

Differential Effects of Oxycodone, Hydrocodone, and Morphine on Activation Levels of Signaling Molecules

“…Different opioids have been shown to activate ERK differently [35]. Additionally, oxycodone and morphine have been demonstrated to differentially activate MOR and have differential pain relieving efficacies in various conditions [36]. Moreover, various opioids can have very different levels of side effects, despite equal potency to relieve pain [7,37].…”