Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
J Pain. 2018 Dec;19(12):1392-1405. doi: 10.1016/j.jpain.2018.06.004. Epub 2018 Jun 30.
Polytrauma commonly involves concussion (mild traumatic brain injury [mTBI]) and peripheral trauma including limb fractures. Interactions between mTBI and peripheral injuries are poorly understood, both leading to chronic pain and neurobehavioral impairments. To elucidate these interactions, a murine polytrauma model was developed. mTBI alone resulted in similar increased mechanical allodynia in male and female mice. Female fracture and polytrauma groups displayed greater increases in hind paw tactile hypersensitivity for weeks after injury than did the respective male groups. Capsaicin-evoked spontaneous pain behaviors were greater in fracture and polytrauma female mice compared with male mice. The mTBI and polytrauma male mice displayed significant deficits in spatial working memory. All fracture, mTBI, or polytrauma groups had deficits in object recognition memory. Only male mTBI or polytrauma mice showed greater agitation and increased risk-taking behavior in open field testing as well as zero maze tests. Additionally, impaired diffuse noxious inhibitory control was observed in all mTBI and polytrauma mice. The model presented offers clinically relevant features useful for studying persistent pain as well as cognitive and other behavioral changes after TBI including polytrauma. A better understanding of nervous system dysfunction after TBI and polytrauma might help prevent or reduce persistent pain and disability in these patients. PERSPECTIVE: The polytrauma model presented has relevant features of chronic pain and neurobehavioral impairments useful for studying mechanisms involved in their development. This model may have special value in understanding altered descending pain modulation after TBI and polytrauma.
多发伤通常涉及脑震荡（轻度创伤性脑损伤 [mTBI]）和外周创伤，包括四肢骨折。mTBI 和外周损伤之间的相互作用知之甚少，两者都导致慢性疼痛和神经行为障碍。为了阐明这些相互作用，开发了一种小鼠多发伤模型。mTBI 单独导致雄性和雌性小鼠的机械性触诱发痛均增加。与相应的雄性组相比，骨折和多发伤雌性组在受伤后数周内后爪触觉超敏反应增加更为明显。与雄性小鼠相比，骨折和多发伤雌性小鼠的辣椒素诱发自发性疼痛行为更大。mTBI 和多发伤雄性小鼠在空间工作记忆方面存在明显缺陷。所有骨折、mTBI 或多发伤组在物体识别记忆方面均存在缺陷。只有雄性 mTBI 或多发伤小鼠在旷场测试和零迷宫测试中表现出更大的激动和增加的冒险行为。此外，所有 mTBI 和多发伤小鼠均观察到弥漫性伤害性抑制控制受损。提出的模型具有临床相关特征，可用于研究 TBI 后持续性疼痛以及认知和其他行为变化，包括多发伤。更好地了解 TBI 和多发伤后的神经系统功能障碍可能有助于预防或减少这些患者的持续性疼痛和残疾。观点：提出的多发伤模型具有慢性疼痛和神经行为障碍的相关特征，可用于研究其发生机制。该模型在理解 TBI 和多发伤后下行性疼痛调节改变方面可能具有特殊价值。
