Opioid-Induced Hyperalgesia (OIH) Model

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. Where tolerance is driven mainly by opioid receptor desensitization and downregulation, hyperalgesia reflects enhanced pain signaling pathways.

In Transpharmation’s model, mice receive morphine (10 mg/kg) twice daily from day 0 to day 4. Mechanical allodynia (von Frey) and thermal sensitivity (hot plate) are measured before dosing, on day 5 to confirm hyperalgesia and randomize treatment groups, and 1 hour after compound dosing on days 6 and 7. The hyperalgesia appears as early as day 3 and is sustained to at least day 14, giving a robust and repeatable window in both endpoints.

Methadone and buprenorphine serve as positive controls. The model lets clients test whether their compounds reverse established OIH caused by long-term opioid use.

Opioid-induced hyperalgesia (OIH)
Study timeline. Morphine twice daily on days 0 to 4; von Frey and hot plate testing on day 5; compound dosing on day 6, with testing 1 hour later; compound dosing on day 7, with testing 1 hour later.

BID dosing of Morphine (10mg/kg) D0-D4
Primary species: Mouse
Primary endpoint: Mechanical allodynia (von Frey) and Thermal allodynia (hot plate)
Positive control: Methadone, Buprenorphine
Recommended N of 10

Key for both charts: sham (white), vehicle (red), methadone 5 mg/kg (light green) and buprenorphine 2 mg/kg (dark green).
Mouse: von Frey
Bar chart of paw withdrawal threshold (g) at baseline, day 5 (NP) and 1 hour after dosing on days 6 and 7, for four groups. Morphine-treated vehicle mice have a lower paw withdrawal threshold than sham from day 5 to day 7, and methadone 5 mg/kg and buprenorphine 2 mg/kg raise it above vehicle on days 6 and 7.
Mouse: Hot plate
Bar chart of hot plate latency (s) at baseline, day 5 (NP) and 1 hour after dosing on days 6 and 7, for the same groups. Hot plate latency is shorter in vehicle mice than sham, and methadone and buprenorphine lengthen it on day 6, methadone also on day 7.

NP: Day 5
Two-way repeated measure ANOVA with Dunnett's multiple comparisons post-hoc test