Neuropathic pain (NP) is a common complication that negatively affects the lives of patients with spinal cord injury (SCI). The disruption in the balance of excitatory and inhibitory neurons in the spinal cord dorsal horn contributes to the development of SCI and induces NP. The calcium-binding protein (CaBP) calbindin-D 28K (CaBP-28K) is highly expressed in excitatory interneurons, and the CaBP parvalbumin (PV) is present in inhibitory neurons in the dorsal horn. To better define the changes in the CaBPs contributing to the development of SCI-induced NP, we examined the changes in CaBP-28K and PV staining density in the lumbar (L4-6) lamina I and II, and their relationship with NP after mild spinal cord contusion injury in mice. We additionally examined the effects of alternate thermal stimulation (ATS). Compared with sham mice, injured animals developed mechanical allodynia in response to light mechanical stimuli and exhibited mechanical hyporesponsiveness to noxious mechanical stimuli. The decreased response latency to heat stimuli and increased response latency to cold stimuli at 7 days post injury suggested that the injured mice developed heat hyperalgesia and cold hypoalgesia, respectively. Temperature preference tests showed significant warm allodynia after injury. Animals that underwent ATS (15-18 and 35-40°C; +5 minutes/stimulation/day; 5 days/week) displayed significant amelioration of heat hyperalgesia, cold hypoalgesia, and warm allodynia after 2 weeks of ATS. In contrast, mechanical sensitivity was not influenced by ATS. Analysis of the CaBP-28K positive signal in L4-6 lamina I and II indicated an increase in staining density after SCI, which was associated with an increase in the number of CaBP-28K-stained L4-6 dorsal root ganglion (DRG) neurons. ATS decreased the CaBP-28K staining density in L4-6 spinal cord and DRG in injured animals, and was significantly and strongly correlated with ATS alleviation of pain behavior. The expression of PV showed no changes in lamina I and II after ATS in SCI animals. Thus, ATS partially decreases the pain behavior after SCI by modulating the changes in CaBP-associated excitatory-inhibitory neurons.

中文翻译：

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交替热刺激改善热敏感性并调节小鼠脊髓挫伤模型中 I 层和 II 层以及背根神经节中 calbindin-D 28K 的表达

神经性疼痛 (NP) 是一种常见的并发症，对脊髓损伤 (SCI) 患者的生活产生负面影响。脊髓背角兴奋性和抑制性神经元平衡的破坏有助于 SCI 的发展并诱导 NP。钙结合蛋白 (CaBP) calbindin-D 28K (CaBP-28K) 在兴奋性中间神经元中高度表达，而 CaBP 小清蛋白 (PV) 存在于背角的抑制性神经元中。为了更好地定义导致 SCI 诱导的 NP 发展的 CaBP 的变化，我们检查了腰椎 (L4-6) 椎板 I 和 II 中 CaBP-28K 和 PV 染色密度的变化，以及它们与轻度损伤后的 NP 的关系。小鼠脊髓挫伤。我们还检查了交替热刺激 (ATS) 的影响。与假老鼠相比，受伤的动物对轻微的机械刺激产生机械性异常性疼痛，并对有害机械刺激表现出机械反应性低下。损伤后7天对热刺激的反应潜伏期减少和对冷刺激的反应潜伏期增加表明受伤的小鼠分别出现了热痛觉过敏和冷痛觉减退。温度偏好测试显示受伤后出现明显的热异常性疼痛。接受 ATS（15-18 和 35-40°C；+5 分钟/刺激/天；5 天/周）的动物在 ATS 2 周后表现出热痛觉过敏、冷痛觉减退和温异常性疼痛的显着改善。相比之下，机械敏感性不受 ATS 的影响。L4-6 层 I 和 II 中 CaBP-28K 阳性信号的分析表明 SCI 后染色密度增加，这与 CaBP-28K 染色的 L4-6 背根神经节 (DRG) 神经元数量增加有关。ATS 降低了受伤动物 L4-6 脊髓和 DRG 中的 CaBP-28K 染色密度，并且与 ATS 减轻疼痛行为显着且强相关。PV 的表达在 SCI 动物 ATS 后显示出 I 和 II 层没有变化。因此，ATS 通过调节与 CaBP 相关的兴奋性抑制神经元的变化，部分减少了 SCI 后的疼痛行为。