Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
Exp Gerontol. 2023 Nov;183:112321. doi: 10.1016/j.exger.2023.112321. Epub 2023 Nov 3.
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.
衰老是与多种生理器官变化相关的，包括中枢和外周神经系统。有报道称，在不同类型的疼痛模型中，食欲素信号具有潜在的镇痛作用，尤其是炎症性牙髓疼痛。然而，年龄对牙齿疼痛感知和食欲素镇痛的影响尚未完全阐明。在这里，我们测试了衰老如何改变食欲素-A 在大鼠牙髓疼痛模型中对伤害性行为的影响。还评估了年轻和老年大鼠三叉神经尾核（TNC）中食欲素受体和伤害性神经肽 P 物质（SP）和降钙素基因相关肽（CGRP）的表达水平。通过向牙髓内施用辣椒素（100μg）来诱导牙髓疼痛。使用免疫荧光技术评估表达水平。结果表明，与年轻大鼠相比，食欲素-A 改善疼痛感知的效果在老年大鼠中较差。此外，与年轻大鼠相比，老年大鼠 TNC 中食欲素 1 和 2 受体的数量明显减少。在年轻动物的 TNC 中注射食欲素-A 也显著抑制了牙髓疼痛诱导的 SP 和 CGRP 过表达。相比之下，食欲素-A 不能在老年动物中产生这种效果。总之，与年龄相关的食欲素镇痛作用降低可能是由于其受体下调以及食欲素信号不能抑制 SP 和 CGRP 等伤害性神经肽的表达所致。
