Sex differences in a Murine Model of Complex Regional Pain Syndrome.
Sex differences in a Murine Model of Complex Regional Pain Syndrome.
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DOI：
10.1016/j.nlm.2015.06.004
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发表时间：
2015-09
影响因子：
2.7
通讯作者：
David Clark J
中科院分区：
文献类型：
--
作者：
Tajerian M;Sahbaie P;Sun Y;Leu D;Yang HY;Li W;Huang TT;Kingery W;David Clark J
复杂性局部疼痛综合征（CRPS）是手术或肢体创伤后慢性疼痛的主要原因。尽管有证据表明，许多形式的慢性疼痛（包括CRPS）的患病率和严重程度在男性和女性之间存在差异，但尚未获得CRPS动物模型中性别相关差异的实验室研究，并且性别对从急性向慢性CRPS疼痛和残疾转变的影响尚未探索。在这里，我们利用胫骨骨折/铸型小鼠模型，概括了CRPS的伤害性，功能，血管，营养，炎症和免疫方面。我们的目的是描述慢性时间过程中的伤害性，运动和记忆的变化与骨折/管型在雄性和雌性小鼠，除了探索其潜在的脊柱机制。我们的行为数据表明，与雄性相比，雌性小鼠在骨折后表现出较低的伤害性阈值，在持续性或自发性疼痛方面没有任何差异。此外，雌性小鼠表现出夸张的运动功能障碍，恐惧记忆缺陷，以及在伤害性阈值正常化后很久才表现出的潜在致敏迹象。我们的生化数据显示，脊髓谷氨酸受体NR 2b水平的差异，表明中枢致敏机制的性别差异，可以解释两组之间CRPS症状的持续时间和严重程度的差异。
Complex Regional Pain Syndrome (CRPS) is a major cause of chronic pain after surgery or trauma to the limbs. Despite evidence showing that the prevalence and severity of many forms of chronic pain, including CRPS, differ between males and females, laboratory studies on sex-related differences in animal models of CRPS are not available, and the impact of sex on the transition from acute to chronic CRPS pain and disability are unexplored. Here we make use of a tibia fracture/cast mouse model that recapitulates the nociceptive, functional, vascular, trophic, inflammatory and immune aspects of CRPS. Our aim is to describe the chronic time course of nociceptive, motor and memory changes associated with fracture/cast in male and female mice, in addition to exploring their underlying spinal mechanisms. Our behavioral data shows that, compared to males, female mice display lower nociceptive thresholds following fracture in the absence of any differences in ongoing or spontaneous pain. Furthermore, female mice show exaggerated signs of motor dysfunction, deficits in fear memory, and latent sensitization that manifests long after the normalization of nociceptive thresholds. Our biochemical data show differences in the spinal cord levels of the glutamate receptor NR2b, suggesting sex differences in mechanisms of central sensitization that could account for differences in duration and severity of CRPS symptoms between the two groups.