Choi Sheu-Ran, Lee Jaehak, Moon Ji-Young, Baek Seung Joon, Lee Jang-Hern
Department of Pharmacology, Catholic Kwandong University College of Medicine, Gangneung 25601, Korea.
Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.
Exp Neurobiol. 2023 Aug 31;32(4):247-258. doi: 10.5607/en23019.
Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1), also known as growth differentiation factor-15 (GDF-15), is associated with cancer, diabetes, and inflammation, while there is limited understanding of the role of NAG-1 in nociception. Here, we examined the nociceptive behaviors of NAG-1 transgenic (TG) mice and wild-type (WT) littermates. Mechanical sensitivity was evaluated by using the von Frey filament test, and thermal sensitivity was assessed by the hot-plate, Hargreaves, and acetone tests. c-Fos, glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule-1 (Iba-1) immunoreactivity was examined in the spinal cord following observation of the formalin-induced nociceptive behaviors. There was no difference in mechanical or thermal sensitivity for NAG-1 TG and WT mice. Intraplantar formalin injection induced nociceptive behaviors in both male and female NAG-1 TG and WT mice. The peak period in the second phase was delayed in NAG-1 TG female mice compared with that of WT female mice, while there was no difference in the cumulative time of nociceptive behaviors between the two groups of mice. Formalin increased spinal c-Fos immunoreactivity in both TG and WT female mice. Neither GFAP nor Iba-1 immunoreactivity was increased in the spinal cord of TG and WT female mice. These findings indicate that NAG-1 TG mice have comparable baseline sensitivity to mechanical and thermal stimulation as WT mice and that NAG-1 in female mice may have an inhibitory effect on the second phase of inflammatory pain. Therefore, it could be a novel target to inhibit central nervous system response in pain.
非甾体抗炎药激活基因-1（NAG-1），也被称为生长分化因子-15（GDF-15），与癌症、糖尿病和炎症相关，而人们对NAG-1在伤害感受中的作用了解有限。在此，我们研究了NAG-1转基因（TG）小鼠和野生型（WT）同窝小鼠的伤害感受行为。通过使用von Frey细丝试验评估机械敏感性，通过热板试验、哈格里夫斯试验和丙酮试验评估热敏感性。在观察福尔马林诱导的伤害感受行为后，检测脊髓中c-Fos、胶质纤维酸性蛋白（GFAP）和离子钙结合衔接分子-1（Iba-1）的免疫反应性。NAG-1 TG小鼠和WT小鼠在机械或热敏感性方面没有差异。足底注射福尔马林在雄性和雌性NAG-1 TG小鼠和WT小鼠中均诱发伤害感受行为。与WT雌性小鼠相比，NAG-1 TG雌性小鼠第二阶段的高峰期延迟，而两组小鼠伤害感受行为的累积时间没有差异。福尔马林增加了TG和WT雌性小鼠脊髓中c-Fos的免疫反应性。TG和WT雌性小鼠脊髓中的GFAP和Iba-1免疫反应性均未增加。这些发现表明，NAG-1 TG小鼠对机械和热刺激的基线敏感性与WT小鼠相当，并且雌性小鼠中的NAG-1可能对炎症性疼痛的第二阶段具有抑制作用。因此，它可能是抑制疼痛中枢神经系统反应的一个新靶点。
