SR 57227A, a serotonin type-3 receptor agonist, as a candidate analgesic agent targeting nociplastic pain
SR 57227A, a serotonin type-3 receptor agonist, as a candidate analgesic agent targeting nociplastic pain
复制标题
SR 57227A，一种 3 型血清素受体激动剂，作为针对伤害性疼痛的候选镇痛剂
DOI：
10.1016/j.bbrc.2022.07.027
复制
发表时间：
2022
影响因子：
3.1
通讯作者：
Shimada Shoichi
中科院分区：
文献类型：
--
作者：
Nakamura Yukiko;Sumi Takuya;Mitani Osamu;Okamoto Takashi;Kubo Erika;Masui Kuniharu;Kondo Makoto;Koyama Yoshihisa;Usui Noriyoshi;Shimada Shoichi
疼痛受多种因素的影响，如恐惧、焦虑和记忆。我们之前报道过，小鼠的疼痛样行为可以由先前存在疼痛刺激的环境线索诱导，并且使用芬太尼（一种阿片类药物）可以减轻疼痛。虽然阿片类镇痛药目前用于治疗持续性疼痛，但在美国，它们的不当使用导致了大量死亡。因此，需要阿片类药物的替代药物。在这里，我们报道了SR 57227A，一种血清素3型受体激动剂，可以显著减少疼痛样行为。SR 57227A减少了PFC中因环境因素而增加的c-Fos阳性细胞的数量。此外，SR 57227A降低了福尔马林试验的疼痛样行为，并通过肌肉注射酸性盐水和坐骨神经结扎恢复了足部戒断阈值的降低。与阿片类药物不同，sr57227a在条件位置偏好测试中没有诱导偏好行为。这些数据表明，SR 57227A是针对慢性疼痛的阿片类药物的有效替代止痛药。
Pain is influenced by various factors, such as fear, anxiety, and memory. We previously reported that pain-like behaviors in mice can be induced by environmental cues in which a pain stimulus was previously presented, and that pain was reduced using fentanyl (an opioid). Although opioid analgesics are currently used to treat persistent pain, their inappropriate use causes a significant number of deaths in the United States. Thus, alternative medicines to opioids are needed. Here, we reported that SR 57227A, a serotonin type-3 receptor agonist, significantly reduced pain-like behaviors. The number of c-Fos positive cells increased by environmental cues in PFC was decreased by SR 57227A. Moreover, SR 57227A reduced pain-like behaviors of the formalin test, and restored reductions in paw withdrawal thresholds by acidic saline intramuscular injection and sciatic nerve ligation. Unlike opioids, SR 57227A induced no preference behaviors as measured by the conditioned place preference test. These data suggested that SR 57227A is an effective alternative pain reliever to opioids that targets chronic pain.