Paw pressure test in the rabbit: a new animal model for the study of pain.
BACKGROUND
In order to develop 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, ketorprofen 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.
Hu
O Y
OY
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Ho
S T
ST
Wang
J J
JJ
Lee
S C
SC
D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D010147:Pain Measurement; D011817:Rabbits
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid