Department of Psychology, University of New England, Biddeford, ME 04005, United States.
Pharmacol Biochem Behav. 2011 Mar;98(1):35-42. doi: 10.1016/j.pbb.2010.12.009. Epub 2010 Dec 10.
Pain stimulates some behaviors (e.g., withdrawal responses) and depresses other behaviors (e.g., feeding and locomotion). We are developing methods for testing candidate analgesics using measurements of pain-depressed behaviors. Such assays may model important aspects of clinical pain and complement traditional procedures that measure pain-stimulated behaviors. The present study characterized the effects of a chronic pain manipulation (monosodium iodoacetate (MIA)-induced osteoarthritis) on wheel running in rats. Rats had 24 h voluntary access to running wheels. Duration of running wheel acquisition was manipulated such that rats had either 21 or 7 days of running wheel access prior to MIA administration. Wheel running was monitored for an additional 21 days following MIA administration. MIA produced concentration- and acquisition length-dependent decreases in wheel running. Parallel experiments demonstrated that MIA produced concentration-dependent tactile allodynia and shifts in hind limb weight bearing. MIA was differentially potent across assays with a potency rank: weight-bearing≥von Frey>running wheel. MIA produced greater depression of wheel running in rats with relatively high baseline running rates compared to rats with relatively low baseline running rates. The differential potency of MIA across assays and apparent rate-dependent effects in running wheels may impact our traditional interpretations of preclinical nociceptive and antinociceptive testing.
疼痛刺激某些行为（例如，退缩反应），而抑制其他行为（例如，进食和运动）。我们正在开发使用疼痛抑制行为测量来测试候选镇痛药的方法。此类测定方法可能模拟临床疼痛的重要方面，并补充测量疼痛刺激行为的传统方法。本研究描述了慢性疼痛操作（碘乙酸单钠（MIA）诱导的骨关节炎）对大鼠跑步轮活动的影响。大鼠有 24 小时自由进入跑步轮。通过操纵跑步轮的获取时间，使大鼠在接受 MIA 之前有 21 天或 7 天的跑步轮使用。在 MIA 给药后，又监测了 21 天的跑步轮活动。MIA 导致轮跑活动呈浓度和获取长度依赖性减少。平行实验表明，MIA 产生了浓度依赖性的触诱发痛和后肢负重的变化。MIA 在不同的测定方法中具有不同的效力，效力等级为：负重>von Frey>跑步轮。与基线跑步率相对较低的大鼠相比，基线跑步率相对较高的大鼠的轮跑活动受到 MIA 的抑制作用更大。MIA 在不同测定方法中的效力差异以及在跑步轮中似乎的速率依赖性效应可能会影响我们对临床前疼痛和镇痛测试的传统解释。
