
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.
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Humanized Models PXB humanized-liver mice
SPIDAR Rapid analgesic screening
Transgenics Genetically modified mice
Have a program in mind?
Talk to a Transpharmation researcher about your study design and timelines.