Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Mol Pain. 2021 Jan-Dec;17:17448069211011326. doi: 10.1177/17448069211011326.
Microglia activation following peripheral nerve injury has been shown to contribute to central sensitization of the spinal cord for the development of neuropathic pain. In a recent study, we reported that the amount of nerve damage does not necessarily correlate with chronic pain development. Here we compared the response of spinal microglia, using immunohistochemistry as a surrogate of microglial activation, in mice with two different types of crush injury of the sciatic nerve. We confirmed that incomplete crush of the sciatic nerve (partial crush injury, PCI) resulted in tactile hypersensitivity after the recovery of sensory function (15 days after surgery), whereas the hypersensitivity was not observed after the complete crush (full crush injury, FCI). We observed that immunoreactivity for Iba-1, a microglial marker, was greater in the ipsilateral dorsal horn of lumbar (L4) spinal cord of mice 2 days after FCI compared to PCI, positively correlating with the intensity of crush injury. Ipsilateral Iba-1 reactivity was comparable between injuries at 7 days with a significant increase compared to the contralateral side. By day 15 after injury, ipsilateral Iba-1 immunoreactivity was much reduced compared to day 7 and was not different between the groups. Our results suggest that the magnitude of the early microgliosis is dependent on injury severity, but does not necessarily correlate with the long-term development of chronic pain-like hypersensitivity after peripheral nerve injury.
外周神经损伤后小胶质细胞的激活被证明有助于脊髓对神经性疼痛的中枢敏化。在最近的一项研究中，我们报告说神经损伤的程度不一定与慢性疼痛的发展相关。在这里，我们比较了两种不同类型坐骨神经挤压伤小鼠的脊髓小胶质细胞反应，用免疫组织化学作为小胶质细胞激活的替代物。我们证实不完全挤压坐骨神经（部分挤压损伤，PCI）导致感觉功能恢复后（手术后 15 天）触觉过敏，而完全挤压（完全挤压损伤，FCI）后则没有观察到这种过敏。我们观察到，FCI 后第 2 天与 PCI 相比，FCI 后同侧 L4 脊髓背角中小胶质细胞标志物 Iba-1 的免疫反应性更强，与挤压损伤的强度呈正相关。损伤后第 7 天，同侧 Iba-1 反应性与损伤侧相似，与对侧相比显著增加。损伤后第 15 天，与第 7 天相比，同侧 Iba-1 免疫反应性明显降低，两组之间无差异。我们的结果表明，早期小胶质细胞增生的程度取决于损伤的严重程度，但与外周神经损伤后慢性痛样过敏的长期发展并不一定相关。
