Department of Human Anatomy, Histology and Embryology and K.K. Leung Brain Research Centre, Air Force Military Medical University, Xi'an, China.
Department of Emergency Medicine, Inner Mongolia Armed Police Corps Hospital, Hohhot, China.
Brain Behav. 2022 Nov;12(11):e2783. doi: 10.1002/brb3.2783. Epub 2022 Oct 9.
Under the condition of stress, the hypothalamic-pituitary-adrenal axis (HPA axis) is activated and causes the secretion of corticotropin-releasing factor (CRF). Previous studies have demonstrated that CRF is involved in the regulation of pain and itch. Thus, it remains worthy to explore whether the desensitization of pain and itch under high-intensity acute stress (such as high fear and tension) is related to the sharp increase of CRF.
Forced swimming was used to simulate acute stress. ELISA and pharmacological methods were conducted to observe the effects of forced swimming on acute pain or itch and the relationship between blood CRF content and itch or pain behavior. Intracerebroventricular (ICV) administration of CRF was conducted to examine the effects of CRF on acute pain or itch. Intrathecal administration of CRF receptor agonist or antagonist was conducted to examine the receptor mechanisms of the regulatory role of CRF in pain and itch.
ELISA experiment showed that the serum CRF in mice reached its peak within 5-10 min after acute stress (forced swimming). Behavioral data showed that the scratching behavior induced by itch agents decreased after acute swimming, while the mechanical pain threshold increased significantly. The inhibitory effect of acute stress on pain and itch is mediated by CRF receptor2 (CRFR2). Then, ICV injection of CRF was used to simulate the massive release of CRF under acute stress, and we observed that the scratching behavior induced by histamine or chloroquine was significantly inhibited after ICV injection of CRF. The above effects of CRF are mainly mediated by CRFR2. These results suggest that 5-10 min after acute stress, a large amount of CRF is released into the blood from the hypothalamus, which significantly inhibits acute pain and itch by acting on CRFR2. ICV injection of CRF can replicate the antipruritus effects of acute stress.
The present study investigated the mechanism of acute stress-induced analgesia and antipruritus and provided theoretical support for the treatment of pain and itch.
在应激条件下，下丘脑-垂体-肾上腺轴（HPA 轴）被激活，导致促肾上腺皮质释放因子（CRF）的分泌。先前的研究表明，CRF 参与了疼痛和瘙痒的调节。因此，探索高强度急性应激（如高度恐惧和紧张）下的疼痛和瘙痒脱敏是否与 CRF 的急剧增加有关，仍然具有重要意义。
采用强迫游泳模拟急性应激。酶联免疫吸附试验（ELISA）和药理学方法观察强迫游泳对急性疼痛或瘙痒的影响，以及血液 CRF 含量与瘙痒或疼痛行为的关系。通过脑室内（ICV）给予 CRF 观察 CRF 对急性疼痛或瘙痒的影响。通过鞘内给予 CRF 受体激动剂或拮抗剂观察 CRF 对疼痛和瘙痒调节作用的受体机制。
ELISA 实验显示，急性应激（强迫游泳）后 5-10 分钟，小鼠血清 CRF 达到峰值。行为学数据显示，瘙痒剂诱导的搔抓行为在急性游泳后减少，而机械痛阈显著增加。急性应激对疼痛和瘙痒的抑制作用是通过 CRF 受体 2（CRFR2）介导的。然后，通过 ICV 注射 CRF 模拟急性应激下 CRF 的大量释放，我们观察到 ICV 注射 CRF 后组胺或氯喹诱导的搔抓行为明显受到抑制。CRF 的上述作用主要是通过 CRFR2 介导的。这些结果表明，急性应激后 5-10 分钟，大量 CRF 从下丘脑释放到血液中，通过作用于 CRFR2 显著抑制急性疼痛和瘙痒。ICV 注射 CRF 可复制急性应激的止痒作用。
本研究探讨了急性应激诱导镇痛和止痒的机制，为疼痛和瘙痒的治疗提供了理论依据。
