Abstract：
Aging is related to a variety of physiological organ changes, including central and peripheral nervous systems. It has been reported that the orexin signaling has a potential analgesic effect in different models of pain, especially inflammatory pulpal pain. However, the age-induced alteration in dental pain perception and orexin analgesia has not yet been fully elucidated. Here, we tested that how aging may change the effect of orexin-A on nociceptive behaviors in a rat dental pulp pain model. The expression levels of orexin receptors and the nociceptive neuropeptides substance P (SP) and calcitonin-related gene peptide (CGRP) were also assessed in the trigeminal nucleus caudalis (TNC) of young and aged rats. Dental pulp pain was induced by intradental application of capsaicin (100 μg). The immunofluorescence technique was used to evaluate the expression levels. The results show less efficiency of orexin-A to ameliorate pain perception in aged rats as compared to young rats. In addition, a significant decrease in the number of orexin 1 and 2 receptors was observed in the TNC of aged as compared to young rats. Dental pain-induced SP and CGRP overexpression was also significantly inhibited by orexin-A injection into the TNC of young animals. In contrast, orexin-A could not produce such effects in the aged animals. In conclusion, the older age-related reduction of the antinociceptive effect of orexin may be due to the downregulation of its receptors and inability of orexin signaling to inhibit the expression of nociceptive neuropeptides such as SP and CGRP in aged rats.
摘要：
衰老与多种生理器官的变化有关,包括中枢和周围神经系统。据报道，食欲素信号在不同的疼痛模型中具有潜在的镇痛作用，尤其是炎性牙髓痛.然而,年龄引起的牙齿疼痛感知和食欲素镇痛改变尚未完全阐明。这里,我们在大鼠牙髓疼痛模型中测试了衰老如何改变食欲素A对伤害性行为的影响。还在年轻和老年大鼠的三叉神经尾核（TNC）中评估了食欲素受体，伤害性神经肽P物质（SP）和降钙素相关基因肽（CGRP）的表达水平。牙髓疼痛是通过在牙内施用辣椒素（100μg）引起的。免疫荧光技术用于评估表达水平。结果表明，与年轻大鼠相比，食欲素A改善老年大鼠疼痛感知的效率较低。此外,与年轻大鼠相比，在老年TNC中观察到食欲素1和2受体的数量显着减少。通过将orexin-A注射到幼年动物的TNC中，也显着抑制了牙科疼痛诱导的SP和CGRP过表达。相比之下,orexin-A不能在老年动物中产生这种作用。总之,与年龄相关的食欲素的抗伤害作用降低可能是由于其受体的下调和食欲素信号无法抑制老年大鼠的伤害性神经肽如SP和CGRP的表达。
