Program in Neurobiology, F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Pain. 2012 Apr;153(4):876-884. doi: 10.1016/j.pain.2012.01.016. Epub 2012 Feb 15.
Inflammatory pain impacts adversely on the quality of life of patients, often resulting in motor disabilities. Therefore, we studied the effect of peripheral inflammation induced by intraplantar administration of complete Freund's adjuvant (CFA) in mice on a particular form of voluntary locomotion, wheel running, as an index of mobility impairment produced by pain. The distance traveled over 1 hour of free access to activity wheels decreased significantly in response to hind paw inflammation, peaking 24 hours after CFA administration. Recovery of voluntary wheel running by day 3 correlated with the ability to support weight on the inflamed limb. Inflammation-induced mechanical hypersensitivity, measured with von Frey hairs, lasted considerably longer than the impaired voluntary wheel running and is not driving; therefore, the change in voluntary behavior. The CFA-induced decrease in voluntary wheel running was dose-dependently reversed by subcutaneous administration of antiinflammatory and analgesic drugs, including naproxen (10-80 mg/kg), ibuprofen (2.5-20mg/kg), diclofenac (1.25-10mg/kg), celecoxib (2.5-20mg/kg), prednisolone (0.62-5mg/kg), and morphine (0.06-0.5mg/kg), all at much lower doses than reported in most rodent models. Furthermore, the doses that induced recovery in voluntary wheel running did not reduce CFA-induced mechanical allodynia, indicating a greater sensitivity of the former as a surrogate measure of inflammatory pain. We conclude that monitoring changes in voluntary wheel running in mice during peripheral inflammation is a simple, observer-independent objective measure of functional changes produced by inflammation, likely more aligned to the global level of pain than reflexive measures, and much more sensitive to analgesic drug effects.
炎症性疼痛会对患者的生活质量产生不利影响，常常导致运动障碍。因此，我们研究了足底注射完全弗氏佐剂（CFA）引起的外周炎症对一种特殊形式的自愿运动（即滚轮运动）的影响，将其作为由疼痛引起的运动障碍的指标。在自由接触活动滚轮的 1 小时内，后爪炎症导致的运动距离显著减少，在 CFA 给药后 24 小时达到峰值。第 3 天恢复自愿滚轮运动与在炎症肢体上承重的能力相关。使用 von Frey 毛发测量的炎症引起的机械性超敏反应持续时间明显长于受损的自愿滚轮运动，且不会导致变化；因此，自愿行为的变化。通过皮下给予抗炎和镇痛药，包括萘普生（10-80mg/kg）、布洛芬（2.5-20mg/kg）、双氯芬酸（1.25-10mg/kg）、塞来昔布（2.5-20mg/kg）、泼尼松龙（0.62-5mg/kg）和吗啡（0.06-0.5mg/kg），可以剂量依赖性地逆转 CFA 引起的自愿滚轮运动减少，这些药物的剂量都远低于大多数啮齿动物模型中报道的剂量。此外，诱导自愿滚轮运动恢复的剂量不会减轻 CFA 引起的机械性痛觉过敏，表明前者作为炎症性疼痛的替代测量指标更为敏感。我们得出结论，监测外周炎症期间小鼠自愿滚轮运动的变化是一种简单、观察者独立的客观测量方法，可测量炎症引起的功能变化，可能比反射性测量更能反映整体疼痛水平，并且对镇痛药物的作用更敏感。
