Victoria Nicole C, Karom Mary C, Murphy Anne Z
Neuroscience Institute, Center for Behavioral Neuroscience, Georgia State University, Atlanta, Ga., USA.
Dev Neurosci. 2015;37(1):1-13. doi: 10.1159/000366273. Epub 2014 Nov 12.
Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants.
先前对大鼠的研究已证实，出生当天（P0）经历的炎性疼痛会降低对急性伤害性、引发焦虑和应激刺激的敏感性。然而，迄今为止，早期生活疼痛对成年后应对慢性应激反应的影响尚不清楚。此外，在受伤时给予吗啡，对减轻成年后行为和激素对急性或慢性应激源反应变化的能力尚未进行研究。对P0期的雄性和雌性斯普拉格-道利大鼠幼崽进行足底注射1%角叉菜胶，或在有或没有吗啡的情况下以相同方式处理。成年后，经历过早期生活疼痛的大鼠对急性应激源的敏感性降低，这表现为在旷场试验的内部区域停留时间增加，在强迫游泳试验（FST）中不动潜伏期延长且不动时间减少。还观察到皮质酮加速恢复到基线水平。在受伤时给予吗啡可完全逆转这种“低反应性”表型。相比之下，在经历7天慢性可变应激后，受伤动物表现出“高反应性”表型，因为它们在FST中开始不动并比对照组花费显著更多时间不动。在受伤时接受吗啡的动物对慢性应激的反应也得到了改善。这些数据表明，对早期生活疼痛的镇痛可预防成年后对急性焦虑和应激刺激的低敏感性以及增加对慢性应激的易感性，并且对婴儿疼痛管理具有重要的临床意义。
