Wang Gexin, Ji Yaping, Lidow Michael S, Traub Richard J
Department of Biomedical Sciences, University of Maryland Dental School, Baltimore, Maryland 21201, USA.
J Pain. 2004 Oct;5(8):440-9. doi: 10.1016/j.jpain.2004.07.003.
Tissue damage during the first few weeks after birth can have profound effects on sensory processing in the adult. We have recently reported that a short-lasting inflammation of the neonatal rat hind paw produces baseline hypoalgesia and exacerbated hyperalgesia after reinflammation of that hind paw in the adult. Because the contralateral hind paw and forepaws also displayed hypoalgesia, we speculated that effects of the initial injury were not somatotopically restricted and would alter visceral sensory processing as well. In the present study we tested this hypothesis by examining the effects of neonatal hind paw injury at P3 or P14 on visceral and somatic sensitivity in the adult rat. In P3 rats, the visceromotor response evoked by colorectal distention in the absence of colonic inflammation was attenuated in carrageenan-treated neonatal rats compared to naive rats. Colonic inflammation in the adult reversed this hypoalgesia and evoked a level of visceral hyperalgesia similar to naive rats. There were no consequences of the P14 injury observed in the adult. In a second experiment, colonic inflammation in naive rats induced viscerosomatic inhibition to thermal stimulation of the forepaw and hind paw. This inhibition was reversed, and the paw withdrawal latency was slightly decreased in neonatal (P3) carrageenan-treated rats. Rats treated on P14 appeared similar to naive rats. These data support the hypothesis that neonatal hind paw injury during a critical period permanently alters sensory processing of multiple sensory modalities in the adult. Animals develop with greater inhibitory processing of somatic and visceral stimuli throughout the neuraxis. However, inflammation in the adult in previously uninjured tissue reverses the hypoalgesia and evokes development of normal hyperexcitability associated with tissue injury.
Trauma experienced by premature infants can lead to alterations in sensory processing throughout life. This study shows that short-term somatic tissue injury to neonatal rats during a well-defined critical period alters several aspects of viscerosensory processing in the adult, demonstrating that injury to one tissue affects sensory processing throughout the body.
出生后头几周的组织损伤会对成年后的感觉处理产生深远影响。我们最近报道，新生大鼠后爪的短期炎症会导致成年后该后爪再次发炎时出现基线痛觉减退和加剧的痛觉过敏。由于对侧后爪和前爪也表现出痛觉减退，我们推测初始损伤的影响并非躯体定位受限，也会改变内脏感觉处理。在本研究中，我们通过检查出生后第3天或第14天新生大鼠后爪损伤对成年大鼠内脏和躯体敏感性的影响来验证这一假设。在出生后第3天的大鼠中，与未处理的大鼠相比，角叉菜胶处理的新生大鼠在无结肠炎症时由结肠扩张诱发的内脏运动反应减弱。成年大鼠的结肠炎症逆转了这种痛觉减退，并诱发了与未处理大鼠相似程度的内脏痛觉过敏。在成年大鼠中未观察到出生后第14天损伤的后果。在第二个实验中，未处理大鼠的结肠炎症诱导了对前爪和后爪热刺激的内脏-躯体抑制。这种抑制在出生后第3天用角叉菜胶处理的新生大鼠中被逆转，并且爪退缩潜伏期略有缩短。出生后第14天处理的大鼠表现与未处理大鼠相似。这些数据支持这样的假设，即在关键时期新生大鼠后爪损伤会永久性改变成年大鼠多种感觉模式的感觉处理。动物在整个神经轴上对躯体和内脏刺激的抑制性处理会更强。然而，成年时先前未损伤组织的炎症会逆转痛觉减退，并诱发与组织损伤相关的正常过度兴奋的发展。
早产儿经历的创伤可导致终生感觉处理改变。本研究表明，在明确的关键时期对新生大鼠进行短期躯体组织损伤会改变成年大鼠内脏感觉处理的几个方面，表明一个组织受到损伤会影响全身的感觉处理。
