Motamedi-Manesh Atefeh, Khazaei Sepideh, Bahrami Anahita, Moradi Meysam, Moradi Hamed, Sayad-Deghatkar Ramel, Vaseghi Salar
Cognitive Neuroscience Lab, Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, P.O. Box: 1419815477, Karaj, Iran.
Science and Research Branch, Islamic Azad University, Tehran, Iran.
Exp Brain Res. 2025 Aug 18;243(9):196. doi: 10.1007/s00221-025-07145-1.
Evidence has shown a wide range of changes in pain perception in posttraumatic stress disorder (PTSD). The present study aimed to explore changes in thermal pain threshold in both sexes of rats exposed to electrical footshocks in different periods after fear conditioning. Fear conditioning (PTSD-like model) was induced by three footshocks (0.8 mA, 3 s) paired with sounds (75 dB, 3 s). Extinction was performed using twenty sounds (75 dB, 3 s) with no footshocks, 1 h after footshocks. Freezing and pain threshold were measured 2 h, 2 days, 7 days, or 30 days after PTSD or extinction (there was not any recall session). The results showed freezing behavior showed a downward trend over time in males, while an upward trend over time in females. Extinction slightly decreased freezing behavior in males, while significantly decreased it in females. Pain threshold was increased in male PTSD rats, while after 30days, there was no change in pain perception. In females, pain threshold was restored in both PTSD-7d and - 30d groups. Extinction decreased pain threshold in males, with stronger effect in females. BDNF was decreased and GSK-3beta was increased in male PTSD rats, except PTSD-30d only for BDNF. In females, BDNF level was restored in both PTSD-7d and - 30d, and also, increased in PTSD-2d group, while GSK-3beta was increased. In conclusion, significant sex differences were observed in freezing behavior, pain threshold, and BDNF. Notably, it seems that GSK-3beta may be involved in freezing and pain perception changes only in females exposed to extinction session.
有证据表明创伤后应激障碍（PTSD）患者的疼痛感知存在广泛变化。本研究旨在探讨在恐惧条件反射后的不同时间段接受电击足底刺激的雌雄大鼠热痛阈值的变化。通过三次电击（0.8 mA，3秒）与声音（75分贝，3秒）配对诱导恐惧条件反射（类PTSD模型）。电击后1小时，使用20次无电击的声音（75分贝，3秒）进行消退训练。在PTSD或消退训练后2小时、2天、7天或30天测量僵住行为和疼痛阈值（没有任何回忆环节）。结果显示，雄性大鼠的僵住行为随时间呈下降趋势，而雌性大鼠则呈上升趋势。消退训练使雄性大鼠的僵住行为略有下降，而使雌性大鼠的僵住行为显著下降。雄性PTSD大鼠的疼痛阈值升高，而30天后，疼痛感知没有变化。在雌性大鼠中，PTSD - 7天和 - 30天组的疼痛阈值均恢复。消退训练降低了雄性大鼠的疼痛阈值，对雌性大鼠的影响更强。雄性PTSD大鼠中，除了PTSD - 30天组仅BDNF降低外，BDNF降低而GSK - 3β升高。在雌性大鼠中，PTSD - 7天和 - 30天组的BDNF水平均恢复，并且在PTSD - 2天组中也升高，而GSK - 3β升高。总之，在僵住行为、疼痛阈值和BDNF方面观察到显著的性别差异。值得注意的是，似乎GSK - 3β可能仅在接受消退训练的雌性大鼠的僵住行为和疼痛感知变化中起作用。
