Opioid-Induced Pain

Opioid-induced hyperalgesia (OIH) and opioid-induced tolerance (OIT) are paradoxical, centrally mediated phenomena in which chronic or high-dose opioid exposure sensitizes pain pathways and progressively reduces analgesic efficacy, posing a major challenge for long-term opioid therapy and a key differentiation point for next-generation non-opioid or opioid-sparing analgesics.

Transpharmation offers mouse models of OIH and OIT based on repeated opioid dosing paradigms, capturing both the paradoxical hypersensitivity and the loss of analgesic response over time, enabling robust evaluation of compounds designed to mitigate opioid-related liabilities or serve as opioid-sparing alternatives.

Models

Opioid-induced hyperalgesia (OIH),

In opioid-induced hyperalgesia, prolonged opioid use paradoxically increases sensitivity to pain: rather than needing more opioid for the same effect, the patient experiences more pain at the same or higher doses. In Transpharmation’s model, mice receive morphine (10 mg/kg) twice daily from day 0 to day 4. Methadone and buprenorphine serve as positive controls. The model lets clients test whether their compounds reverse established OIH caused by long-term opioid use.

Read the full description: Opioid-induced hyperalgesia (OIH)

Opioid-induced tolerance (OIT),

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. The model lets clients compare the tolerance their compounds produce with that of morphine, or test a compound’s ability to attenuate tolerance.

Read the full description: Opioid-induced tolerance (OIT)

Platforms used

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