Zuqing Zhu , Gang Chen , Jiangtao He , Yuanting Xu
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Abstract
Chronic pain induced by pathological insults to the sensorimotor system is a typical form of neuropathic pain (NP), and the underlying mechanism is complex. Currently, there are no successful therapeutic interventions for NP. Orexin B is a neuropeptide with a wide range of biological functions. However, the pharmacological function of orexin B in chronic neuropathic pain has been less studied. Here, we aim to examine the neuroprotective effects of orexin B in chronic constriction injury (CCI)- induced NP. Firstly, we found that orexin type 2 receptor (OX2R) but not orexin type 1 receptor (OX1R) was reduced in the spinal cord (SC) of CCI-treated rats. Mechanical withdrawal threshold and thermal withdrawal latency assays display that administration of orexin B clearly ameliorated CCI-evoked neuropathic pain dose-dependently. Notably, orexin B treatment also effectively prevented microglia activation by reducing the levels of IBA1. Additionally, orexin B was also found to suppress the inflammatory response in the SC tissue by reducing the levels of IL-6, TNF-α, iNOS, and COX-2 as well as the production of NO and PGE2 in CCI-treated rats. Furthermore, orexin B administration attenuated oxidative stress (OS) by increasing the activity of SOD and the levels of GSH. Mechanically, orexin B prevented activation of JNK/NF-κB signaling in the SC of CCI-treated rats. Based on these findings, we conclude that orexin B might have a promising role in ameliorating CCI-evoked neuropathic pain through the inhibition of microglial activation and inflammatory response.
感觉运动系统受到病理损伤而诱发的慢性疼痛是神经病理性疼痛（NP）的一种典型形式，其潜在机制十分复杂。目前，还没有成功治疗 NP 的干预措施。Orexin B 是一种神经肽，具有广泛的生物学功能。然而，关于奥曲肽 B 在慢性神经病理性疼痛中的药理功能研究较少。在此，我们旨在研究奥曲肽 B 在慢性收缩性损伤（CCI）诱导的 NP 中的神经保护作用。首先，我们发现在经 CCI 处理的大鼠脊髓（SC）中，奥曲肽 2 型受体（OX2R）减少，而奥曲肽 1 型受体（OX1R）没有减少。机械戒断阈值和热戒断潜伏期实验表明，给予奥曲肽 B能明显改善CCI诱发的神经病理性疼痛，且呈剂量依赖性。值得注意的是，奥曲肽 B 还能通过降低 IBA1 的水平有效阻止小胶质细胞的激活。此外，研究还发现奥曲肽 B 还能抑制 SC 组织中的炎症反应，降低 CCI 治疗大鼠体内 IL-6、TNF-α、iNOS 和 COX-2 的水平以及 NO 和 PGE2 的产生。此外，奥曲肽 B 还能提高 SOD 的活性和 GSH 的水平，从而减轻氧化应激（OS）。从机理上讲，奥曲肽 B 可阻止 JNK/NF-κB 信号在 CCI 治疗大鼠 SC 中的激活。基于这些发现，我们认为奥曲肽 B 可通过抑制小胶质细胞活化和炎症反应来改善 CCI 诱发的神经病理性疼痛。
期刊介绍：
The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems.
The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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