Department of Psychology, College of Liberal Arts, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.
Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.
J Neurotrauma. 2023 May;40(9-10):833-844. doi: 10.1089/neu.2022.0482. Epub 2023 Mar 14.
Spinal cord injury (SCI) in humans frequently causes intractable chronic pain. Females are susceptible to worse pain than males, and females may show higher pain prevalence after SCI. Despite this difference in the clinical prevalence of SCI pain, few pre-clinical studies have systematically studied sex differences in SCI-elicited pain-related behaviors in rodents. Here, we leverage data from a large cohort of mice to test whether contusion SCI consistently causes pain symptoms in mice, and to establish whether female (vs. male) mice display heightened hypersensitivity after SCI. Mechanical and heat sensory thresholds were assessed using the von Frey and Hargreaves tests, respectively. In an initial experiment, female mice receiving moderate 60 kDyn SCI or moderate-to-severe 75 kDyn SCI at T9 both exhibited mechanical and heat pain symptoms compared with sham controls. A 75 kDyn SCI caused excess motor deficits that confounded defining pain sensitivity at acute times; therefore, the moderate SCI force was used for subsequent experiments. Next, adult female and male C57BL6/J mice received sham surgery or T9 moderate contusion SCI. Comparing female to male mice after SCI, we reveal that mice of both sexes displayed mechanical and heat hypersensitivity compared with sham controls, from acute-to-chronic post-injury times. Females had amplified SCI-elicited hypersensitivity compared with males. Our data suggest that thoracic contusion SCI elicits consistent and persistent pain-associated symptoms, which are more intense in female than in male mice. These results have important implications for uncovering sex-specific mechanisms and therapeutic targets to ameliorate neuropathic pain after SCI.
脊髓损伤（SCI）在人类中常导致难治性慢性疼痛。女性比男性更容易受到疼痛的影响，且女性在 SCI 后可能表现出更高的疼痛发生率。尽管 SCI 疼痛的临床发生率存在这种差异，但很少有临床前研究系统地研究了 SCI 诱发的啮齿动物疼痛相关行为中的性别差异。在这里，我们利用大量小鼠的数据来测试挫伤性 SCI 是否会持续引起小鼠的疼痛症状，并确定雌性（与雄性）小鼠在 SCI 后是否表现出更高的过敏反应。使用 von Frey 和 Hargreaves 测试分别评估机械和热感觉阈值。在一项初步实验中，接受 T9 中度 60 kDyn SCI 或中度至重度 75 kDyn SCI 的雌性小鼠与假手术对照组相比，均表现出机械和热痛症状。75 kDyn SCI 引起的过度运动缺陷混淆了急性时疼痛敏感性的定义；因此，后续实验使用中度 SCI 力。接下来，成年雌性和雄性 C57BL6/J 小鼠接受假手术或 T9 中度挫伤 SCI。与 SCI 后雄性小鼠相比，我们发现雌性和雄性小鼠均表现出机械和热敏感性过敏，从急性到慢性损伤后时间。雌性小鼠比雄性小鼠表现出更强的 SCI 诱发的过敏反应。我们的数据表明，胸椎挫伤 SCI 会引起一致且持续的疼痛相关症状，在雌性小鼠中比在雄性小鼠中更为强烈。这些结果对于揭示 SCI 后改善神经性疼痛的性别特异性机制和治疗靶点具有重要意义。
