Paw pressure test in the rabbit: A new animal model for the study of pain

Background: In order to develope an animal model which is suitable for the pharmacokinetic (PK) and pharmacodynamic (PD) studies of analgesics in the field of pain assessment, we examined a new animal model, the paw pressure test (PPT), in rabbits for the study of pain. Methods : The sensitivity of the model was tested with a broad range of drugs, including mu-opioid agonist (morphine), kappa-opioid agonist (nalbuphine), three non-opioid analgesics (acetaminophen, ketoprofen and indomethacin) and two non-analgesics (droperidol and diazepam). Furthermore, PK and PD studies of nalbuphine (chosen as an example of analgesics) were performed. Results : The authors found that the PPT in rabbits recognized the antinociceptive activities of both opioid and non-opioid analgesics with no positive response to non-analgesics. AD50s determined by the PPT in rabbits for morphine and nalbuphine were 3.1 and 8.4 mg/kg, respectively. In the PK and PD studies, the plasma concentration time profiles of nalbuphine were well fitted to a linear two-compartment open model, and the correlation between pharmacokinetics and pharmacodynamics was significant (p < 0.05). Conclusions : These results suggest that the PPT in rabbits can be used extensively to explore the analgesic effects (PD) of a broad range of analgesics. Also, with this model, PK and PD studies of analgesics can be easily performed.