Opioid-Induced Tolerance (OIT) Model

Pain is a major social issue requiring the continuous development of new analgesics. With a lack of effective and safe non-opioid options for pain management, the use of drugs with opioid-based mechanisms of action remains widespread and is associated with numerous adverse effects, including a high risk of substance abuse in some people. Opioid misuse has developed in recent years, leading to a public health crisis. When taken in the prescribed quantities and for a short duration, opioids do not usually result in serious health complications, but their use to excess, compulsive intake or prolonged self-administration can lead, among other issues, to tolerance.

The morphine-induced tolerance assay is widely used for revealing the potency of a new chemical entity to induce a tolerance phenomenon in conscious mice.

In Transpharmation’s model, mice receive morphine (10 mg/kg) twice daily from day 0. The analgesic effect of a morphine dose is measured by hot plate and von Frey 30 minutes after dosing on day 0, and again on day 3, by which point it has fallen significantly. On day 4 the test compound is given with the morning morphine dose to measure whether it restores morphine’s analgesic effect.

Ketamine and dexmedetomidine serve as positive controls, each fully restoring morphine analgesia on day 4. The model lets clients compare the tolerance their compounds produce with that of morphine, or test a compound’s ability to attenuate tolerance.