AstraZeneca R&D Montreal, Canada.
Eur J Pain. 2013 Feb;17(2):210-22. doi: 10.1002/j.1532-2149.2012.00176.x. Epub 2012 Sep 11.
Previous pharmacological validations of the rat mono-iodoacetate (MIA)-induced chronic joint pain model were mostly performed by measuring weight-bearing (WB) deficit with an incapacitance tester. However, conventional incapacitance testers have several drawbacks including restrain stress on animal and sole use of hind limbs WB.
The aim of the present study was to compare pharmacological sensitivity of the early (up to 1 week after MIA) versus late (between 2 and 4 weeks after MIA) phase of the rat MIA model using a highly sensitive tactile pressure measurement system (Tekscan(®)), which can measure weight borne by all four limbs and the tail in a non-restrained animal.
The Tekscan(®) WB measurement system was used in MIA rats to examine the acute and chronic dosing effects of drugs that targeted different mechanisms. Electrophysiological recordings from joint afferents and biochemical analysis of synovial fluid were also performed.
Dexamethasone, duloxetine and morphine significantly alleviated WB deficits in the Tekscan(®) system during both early and late phase of the MIA model while celecoxib and naproxen alleviated WB deficit only during the early phase. Similarly, naproxen was able to inhibit spontaneous neuronal activity from MIA joint afferents only during the early phase. Finally, concentrations of prostaglandin E(2) in synovial fluid were elevated only during the early phase of the rat MIA model.
Our pharmacological validation studies using the Tekscan(®) system along with electrophysiological and biochemical results suggest different mechanisms for early and late phase of MIA-induced chronic joint pain in rat.
先前对大鼠单碘乙酸（MIA）诱导的慢性关节疼痛模型的药理学验证大多是通过使用电容测痛仪测量负重（WB）缺陷来进行的。然而，传统的电容测痛仪有几个缺点，包括对动物的束缚应激和仅使用后肢的 WB。
本研究的目的是使用高度敏感的触觉压力测量系统（Tekscan（®））比较大鼠 MIA 模型的早期（MIA 后 1 周内）与晚期（MIA 后 2 至 4 周之间）的药物敏感性，该系统可以测量非束缚动物的所有四肢和尾巴承受的重量。
使用 Tekscan（®）WB 测量系统在 MIA 大鼠中检查靶向不同机制的药物的急性和慢性给药效果。还进行了关节传入神经的电生理记录和滑液的生化分析。
地塞米松、度洛西汀和吗啡在 MIA 模型的早期和晚期均显著缓解了 Tekscan（®）系统中的 WB 缺陷，而塞来昔布和萘普生仅在早期缓解了 WB 缺陷。同样，萘普生仅在 MIA 关节传入神经的早期阶段能够抑制自发性神经元活动。最后，关节滑液中前列腺素 E（2）的浓度仅在大鼠 MIA 模型的早期阶段升高。
我们使用 Tekscan（®）系统进行的药理学验证研究以及电生理和生化结果表明，大鼠 MIA 诱导的慢性关节疼痛的早期和晚期阶段存在不同的机制。
