Rapid cleavage of IL-1β in DRG neurons produces tissue injury-induced pain hypersensitivity.

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Daisuke Fujita, Yutaka Matsuoka, Shunsuke Yamakita, Yasuhiko Horii, Daiki Ishikawa, Kohsuke Kushimoto, Hiroaki Amino, Fumimasa Amaya
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引用次数: 0

Abstract

Background: IL-1β plays a critical role in the pathophysiology of neuroinflammation. The presence of cleaved IL-1β (cIL-1β) in the neurons of the dorsal root ganglion (DRG) implicates its function in biological signaling arising from the sensory neuron. This study was conducted to analyze the role of IL-1β in nociceptive transduction after tissue injury. Methods: A plantar incision was made in C57BL/6 mice, following which immunohistochemistry and RNA scope in situ hybridization were performed at various time points to analyze cIL-1β, caspase-1, and IL-1 receptor 1 (IL-1R1) expression in the DRG. The effect of intrathecal administration of a caspase-1 inhibitor or regional anesthesia using local anesthetics on cIL-1β expression and pain hypersensitivity was analyzed by immunohistochemistry and behavioral analysis. ERK phosphorylation was also analyzed to investigate the effect of IL-1β on the activity of spinal dorsal horn neurons. Results: cIL-1β expression was significantly increased in caspase-1-positive DRG neurons 5 min after the plantar incision. Intrathecal caspase-1 inhibitor treatment inhibited IL-1β cleavage and pain hypersensitivity after the plantar incision. IL-1R1 was also detected in the DRG neurons, although the majority of IL-1R1-expressing neurons lacked cIL-1β expression. Regional anesthesia using local anesthetics prevented cIL-1β processing. Plantar incision-induced phosphorylation of ERK was inhibited by the caspase-1 inhibitor. Conclusion: IL-1β in the DRG neuron undergoes rapid cleavage in response to tissue injury in an activity-dependent manner. Cleaved IL-1β causes injury-induced functional activation of sensory neurons and pain hypersensitivity. IL-1β in the primary afferent neurons is involved in physiological nociceptive signal transduction.

DRG 神经元中 IL-1β 的快速裂解会产生组织损伤诱导的痛觉过敏。
背景 IL-1β 在神经炎症的病理生理学中起着关键作用。背根神经节(DRG)神经元中存在裂解的 IL-1β(cIL-1β),这表明它在感觉神经元发出的生物信号中发挥着作用。本研究旨在分析 IL-1β 在组织损伤后痛觉传导中的作用。方法 对 C57BL/6 小鼠进行足底切口,然后在不同时间点进行免疫组化和 RNA 范围原位杂交,分析 DRG 中 cIL-1β、caspase-1 和 IL-1 受体 1(IL-1R1)的表达。通过免疫组化和行为分析,分析了鞘内注射caspase-1抑制剂或使用局麻药进行区域麻醉对cIL-1β表达和痛觉过敏性的影响。此外,还分析了 ERK 磷酸化,以研究 IL-1β 对脊髓背角神经元活性的影响。结果 足底切口 5 分钟后,caspase-1 阳性的 DRG 神经元中 cIL-1β 表达明显增加。鞘内caspase-1抑制剂可抑制IL-1β的裂解和足底切口后的痛觉过敏。尽管大多数表达IL-1R1的神经元缺乏cIL-1β表达,但在DRG神经元中也检测到了IL-1R1。使用局部麻醉剂进行区域麻醉可阻止 cIL-1β 的处理。caspase-1 抑制剂抑制了足底切口诱导的 ERK 磷酸化。结论 DRG 神经元中的 IL-1β 在组织损伤时以活动依赖的方式迅速裂解。裂解的 IL-1β 会导致损伤诱导的感觉神经元功能激活和痛觉过敏。初级传入神经元中的 IL-1β 参与了生理痛觉信号转导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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