Department of Anesthesiology and Pain Management, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Dev Psychobiol. 2024 Apr;66(3):e22478. doi: 10.1002/dev.22478.
Exposure to repetitive painful procedures in the neonatal intensive care unit results in long-lasting effects, especially visible after a "second hit" in adulthood. As the nociceptive system and the hypothalamic-pituitary-adrenal (HPA) axis interact and are vulnerable in early life, repetitive painful procedures in neonates may affect later-life HPA axis reactivity. The first aim of the present study was to investigate the effects of repetitive neonatal procedural pain on plasma corticosterone levels after mild acute stress (MAS) in young adult rats. Second, the study examined if MAS acts as a "second hit" and affects mechanical sensitivity. Fifty-two rats were either needle pricked four times a day, disturbed, or left undisturbed during the first neonatal week. At 8 weeks, the animals were subjected to MAS, and plasma was collected before (t0), after MAS (t20), and at recovery (t60). Corticosterone levels were analyzed using an enzyme-linked immunosorbent assay, and mechanical sensitivity was assessed with von Frey filaments. Results demonstrate that repetitive neonatal procedural pain reduces stress-induced plasma corticosterone increase after MAS only in young adult females and not in males. Furthermore, MAS does not affect mechanical sensitivity in young adult rats. Altogether, the results suggest an age- and sex-dependent effect of repetitive neonatal procedural pain on HPA axis reprogramming.
新生儿重症监护病房中反复出现的疼痛操作会导致持久的影响，尤其是在成年后再次受到“打击”时。由于伤害性感受系统和下丘脑-垂体-肾上腺（HPA）轴在生命早期相互作用且易受影响，新生儿反复出现的疼痛操作可能会影响其成年后 HPA 轴的反应性。本研究的首要目的是探讨新生儿反复程序性疼痛对年轻成年大鼠轻度急性应激（MAS）后血浆皮质酮水平的影响。其次，研究还考察了 MAS 是否作为“二次打击”影响机械敏感性。52 只大鼠在新生儿期的第一周内每天接受 4 次针刺、干扰或不干扰。在 8 周时，对动物进行 MAS，并在应激前（t0）、MAS 后（t20）和恢复时（t60）采集血浆。使用酶联免疫吸附试验分析皮质酮水平，用 von Frey 纤维测量机械敏感性。结果表明，在年轻成年雌性大鼠中，反复的新生儿程序性疼痛会降低 MAS 后应激诱导的血浆皮质酮增加，但在雄性大鼠中则没有。此外，MAS 并不影响年轻成年大鼠的机械敏感性。总之，这些结果表明，反复的新生儿程序性疼痛对 HPA 轴重编程具有年龄和性别依赖性的影响。
