Background: Integrins, important extracellular matrix (ECM) receptor proteins, are affected by inflammation and can participate in the maintenance of many painful conditions. Although they are ubiquitous and changeable across all cell types, the roles of these cell adhesion molecules in pathological pain have not been fully explored. Objective: We evaluated the effects of the subcutaneous injection of lebecetin, a C-type lectin isolated from Macrovipera lebetina snake venom, previously reported to inhibit α5β1 and αv integrin activity, on different components of inflammation induced by the formalin administration in the hind paw of mice. Methods: The formalin-induced nocifensive behavior, edema, and histopathological changes in the hind paw associated with cytokine, iNOS, and COX2 expression, nociceptive-specific neuron activity, and microglial activation analysis in the spinal cord were evaluated in mice receiving vehicle or lebecetin pretreatment. Results: Lebecetin inhibited the nocifensive responses in the formalin test, related edema, and cell infiltration in the injected paw in a biphasic, hormetic-like, and dose-dependent way. According to that hormetic trend, a reduction in pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha and upregulation of the anti-inflammatory cytokine IL-10 in the spinal cord were found with the lowest doses of lebecetin. Moreover, COX2 and iNOS expression in serum and spinal cord followed the same biphasic pattern of cytokines. Finally, nociceptive neurons sensitization and activated microglia were normalized in the dorsal horn of the spinal cord by lebecetin. Conclusion: These findings implicate specific roles of integrins in inflammation and tonic pain, as well as in the related central nervous system sequelae.

中文翻译：

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Lebecetin（一种蛇毒 C 型凝集素）对福尔马林诱导的小鼠炎症的双相激效作用

背景：整合素是重要的细胞外基质 (ECM) 受体蛋白，受炎症影响，可参与许多疼痛状况的维持。尽管它们在所有细胞类型中普遍存在且可变，但这些细胞粘附分子在病理疼痛中的作用尚未得到充分探索。目的：我们评估了皮下注射 lebecetin（一种从 Macrovipera lebetina 蛇毒中分离出来的 C 型凝集素，先前报道可抑制 α5β1 和 αv 整合素活性）对福尔马林注射后爪引起的不同炎症成分的影响。老鼠。方法：在接受载体或lebecetin的小鼠中评估福尔马林诱导的伤害行为、水肿和与细胞因子、iNOS和COX2表达相关的后爪组织病理学变化、伤害感受特异性神经元活性以及脊髓中小胶质细胞活化分析预处理。结果：Lebecetin 以双相、类兴奋剂和剂量依赖性方式抑制福尔马林试验中的伤害反应、相关水肿和注射爪子中的细胞浸润。根据这种毒效效应趋势，最低剂量的lebecetin发现脊髓中促炎细胞因子IL-6、IL-8和TNF-α的减少以及抗炎细胞因子IL-10的上调。此外，血清和脊髓中COX2和iNOS的表达遵循相同的细胞因子双相模式。最后，lebecetin 使脊髓背角的伤害性神经元敏化和活化的小胶质细胞正常化。结论：这些发现表明整合素在炎症和强直性疼痛以及相关中枢神经系统后遗症中的特定作用。