Paw Pressure Test in the Rabbit: A New Animal Model for the Study of Pain

白兔壓掌試驗：研究疼痛之新動物模式

胡幼圃(Oliver Yoa-Pu Hu) ； 何善台(Shung-Tai Ho) ； 王志中(Jhi-Joung Wang) ； 李世俊(Shih-Chun Lee)

《Acta Anaesthesiologica Sinica》 34卷1期 (1996/03) Pp. 1-8

https://doi.org/10.6955/AAS.199603.0001

摘要

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 (nalhuphine), 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. AD_(50^S) 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.

關鍵字

Measurement of pain: paw pressure test (PPT) ； Disease model: animal ； Pain ； Opioid ； Biopharmaceutics: pharmacokinetics ； Pharmacology: pharmacodynamics

並列摘要

背景：為了找尋一個動物模式，可以同時進行以藥物動力學及藥效學方式來研究疼痛機轉。本文作者發展了一個新的動物模式，以紐西蘭白兔來進行急性疼痛機轉之研究。方法：我們以多種藥物來證實此動物模式的靈敏性，其中包括類鴉片藥物mu接受體親和劑：嗎啡，kappa接受體親和劑：nalbuphine，非類鴉片之止痛劑：acetaminophen，ketoprofen及indomethacin，及非止痛劑：droperidol，diazepam。另外，藥物動力學及藥效學也同時進行。結果：本動物模式可以偵測類鴉片類止痛劑及非類鴉片止痛劑之止痛作用，而對於非止痛劑則無效。50％之止痛療效在嗎啡為3.1毫克/公斤肌肉注射，而在nalbuphine為8.4毫克/公斤。在藥物動力學及藥效學方面，血中nalbuphine濃度可以用二室式藥物動力學模式來解釋，並且和藥效學間有良好的相關性。結論：由本研究結果推論，白兔壓掌試驗可用來偵測多類之止痛劑的止痛作用，且適用來做為藥物動力學及藥效學之探討。

並列關鍵字

疼痛測量：壓掌試驗 ； 疾病模式：動物 ； 疼痛 ； 類鴉片藥物 ； 生物製藥學：藥物動力學