Morphine, Oxycodone, and Fentanyl Exhibit Different Analgesic Profiles in Mouse Pain Models

Abstract

Abstract. Morphine, oxycodone, and fentanyl are clinically prescribed drugs for the management of severe pain. We investigated whether these opioids possess different efficacy profiles on several types of pain in mouse pain models. When the three opioids were tested in the femur bone cancer model, all of them significantly reversed guarding behavior, whereas the effects on limb-use abnormality and allodynia-like behavior differed among the opioids. Particularly, although oxycodone (5 -20 mg/kg) and fentanyl (0.2 mg/kg) significantly reversed limb-use abnormality, not even a high dose of morphine (50 mg/kg) could reverse it. When the effects of these opioids were examined in a sciatic nerve ligation (SNL) model of neuropathic pain, oxycodone was the most effective, producing an antinociceptive effect without affecting the withdrawal threshold of sham-treated animals. When the effects of these opioids were examined with the tail-flick test using naive animals, oxycodone, morphine, and fentanyl exhibited antinociceptive effects on thermal nociception. These results show that the three opioids exhibit different efficacy outcomes in multiple pain models and that the efficacy profile of oxycodone does not overlap those of morphine and fentanyl.

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

“…To prepare the FBC model, NCTC 2472 tumor cells were injected as described previously (8,10). Briefly, C3H/HeN mice were anesthetized with 3% isoflurane, and left knee arthrotomy performed.…”

“…In the sham group, 5 ml of Hank's balanced salt solution was injected instead of the tumor cells in the same manner. The effects of opioids were assessed 14 days after tumor implantation, which is the optimal time for evaluation of allodynia in this model (10). Allodynia-like behavior was recognized as ipsilateral paw withdrawal in response to tactile stimuli using a series of von-Frey monofilaments (pressure: 0.008, 0.02, 0.04, 0.07, 0.16, 0.4, 0.6, and 1 g).…”

“…Allodynia-like behavior was recognized as ipsilateral paw withdrawal in response to tactile stimuli using a series of von-Frey monofilaments (pressure: 0.008, 0.02, 0.04, 0.07, 0.16, 0.4, 0.6, and 1 g). The up-down method of the von-Frey monofilament test was used as described previously (10).…”

“…The FBC model is produced by injecting osteolytic sarcoma cells into the intra-medullary space of the mouse left distal femur. Tumor cell growth is correlatively observed with several pain-related behaviors, such as on-going pain, ambulatory pain, and allodynia, considered to be complex pain, followed by neuropathic, nociceptive, and inflammatory pain (10). Using the FBC animal model, we reported previously that oxycodone inhibits all of the on-going, ambulatory, and allodynia pain related behaviors over a similar dose range, whereas morphine and fentanyl have less effect on ambulatory pain (10).…”

A pharmacological and transcriptomic approach to exploring novel pain targets

“…Oxycodone, a commonly used µ opioid receptor agonist, successfully reversed mechanical allodynia, thermal allodynia, as well as weight bearing parameters. Notably, burn injury-induced pain behaviours were relatively opioid-resistant compared with doses required to elicit analgesia in simple nociceptive models (1-2 mg/kg) 303,304 . A requirement for higher opioid doses to achieve effective analgesia has also been noted for human burn patients 305 , suggesting that the pathophysiological mechanisms underpinning burn-injury induced pain incorporate elements that lead to decreased efficacy of opioids.…”