Freeman Katie T, Koewler Nathan J, Jimenez-Andrade Juan M, Buus Ryan J, Herrera Monica B, Martin Carl D, Ghilardi Joseph R, Kuskowski Michael A, Mantyh Patrick W
Neurosystems Center and Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
Anesthesiology. 2008 Mar;108(3):473-83. doi: 10.1097/ALN.0b013e3181649351.
Because of the relative lack of understanding of the mechanisms that drive skeletal pain, the purpose of this study was to adapt a previously validated closed femur fracture model to quantitatively evaluate skeletal pain in female and male rats.
Three-month-old female and male Sprague-Dawley rats were anesthetized, and a stainless steel pin was inserted into the intramedullary space of the left femur. Three weeks later, the rats were reanesthetized, and left femoral diaphyses were fractured using a standardized impactor device. At 1-21 days after fracture, skeletal pain was measured by quantitatively assessing spontaneous guarding, spontaneous flinching, and weight bearing of the fractured hind limb.
Females and males showed highly robust pain behaviors that were maximal at day 1 after fracture and returned gradually to normal nonfractured levels at days 14-21 after fracture. The magnitude of fracture pain was not significantly different at most time points between female and male rats. In both females and males, the pain-related behaviors were attenuated by subcutaneous morphine in a dose-dependent manner.
This model may help in developing a mechanism-based understanding of the factors that generate and maintain fracture pain in both females and males and in translating these findings into new therapies for treating fracture pain.
由于对导致骨骼疼痛的机制了解相对不足,本研究的目的是采用先前验证过的闭合性股骨骨折模型来定量评估雌性和雄性大鼠的骨骼疼痛。
对3个月大的雌性和雄性Sprague-Dawley大鼠进行麻醉,将一根不锈钢针插入左股骨的骨髓腔内。三周后,再次对大鼠进行麻醉,使用标准化冲击装置使左股骨干骨折。在骨折后1至21天,通过定量评估自发护痛、自发退缩和骨折后肢的负重情况来测量骨骼疼痛。
雌性和雄性大鼠均表现出强烈的疼痛行为,在骨折后第1天达到峰值,并在骨折后第14至21天逐渐恢复到正常非骨折水平。在大多数时间点,雌性和雄性大鼠的骨折疼痛程度没有显著差异。在雌性和雄性大鼠中,疼痛相关行为均被皮下注射吗啡以剂量依赖的方式减弱。
该模型可能有助于对雌性和雄性大鼠产生和维持骨折疼痛的因素形成基于机制的理解,并将这些发现转化为治疗骨折疼痛的新疗法。