Comparison of the antinociceptive profiles of morphine and oxycodone in two models of inflammatory and osteoarthritic pain in rat

Abstract

Oxycodone and morphine are two opioid drugs commonly used for the treatment of moderate to severe pain. However, their use in the management of noncancer pain remains a controversial issue and, in this respect, the evidence on their effectiveness and safety, particularly in osteoarthritis, is being questioned. In order to analyse their analgesic profile, two different pain models in rats were used: the formalin-induced inflammatory pain and the monosodium iodoacetate (MIA)-induced knee osteoarthritic pain. Drugs were administered systemically (i.p.) and their antinociceptive effect and potency were assessed. In the formalin test, both morphine and oxycodone produced a dose-dependent antinociceptive effect, but oxycodone outdid morphine in terms of effectiveness and potency (nearly two times) in the early (acute nociceptive) as in the late phase (inflammatory). In the osteoarthritis model, both drugs reduced movement–evoked pain (knee-bend test), mechanical allodynia (von Frey test) and heat hyperalgesia (Plantar test). Pretreatment with naloxone and naloxone methiodide reduced morphine and oxycodone effects. Peripheral mu-opioid receptors play a crucial role in the antinociceptive effect of both drugs on movement-evoked pain and heat hyperalgesia, but not on tactile allodynia. The main finding of our study is that oxycodone has a better antinociceptive profile in the inflammatory and osteoarthritic pain, being more effective than morphine at 14 days post-MIA injection (phase with neuropathic pain); it overcame the morphine effect by improving the movement-induced pain, tactile allodynia and heat hyperalgesia. Therefore, oxycodone could be an interesting option to treat patients suffering from knee osteoarthritis when opioids are required.