IMPLICATIONS: Oxycodone, methadone, and especially l-methadone were more effective than morphine in all studied pain models in the rat, including a model of nerve injury pain. Morphine may not be the most effective opioid, whereas l-methadone could be an interesting option when treating neuropathic pain.

Opioids are the first-line pharmacological treatment for cancer pain. The consumption of opioids has increased significantly since opioids were introduced to the management of chronic noncancer pain. Even though the most commonly used strong opioids such as morphine, oxycodone, and methadone are all μ-opioid receptor agonists (1, 2) they have distinctly different molecular structures and may have different effects in different pathophysiological conditions. However, these opioids have not been compared in standardized conditions in different pain models.