The roles of neurotensin and its analogues in pain.
The roles of neurotensin and its analogues in pain.
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DOI：
10.2174/1381612820666141027124915
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发表时间：
2014-12
影响因子：
3.1
通讯作者：
Yu-Peng Feng;Jian Wang;Yu-Lin Dong;Yayun Wang;Yun-Qing Li
中科院分区：
文献类型：
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作者：
Yu-Peng Feng;Jian Wang;Yu-Lin Dong;Yayun Wang;Yun-Qing Li
神经降压素(Neurotensin，NT)是一种内源性13个氨基酸的神经肽，具有深刻的阿片非依赖性镇痛作用。NT的这一作用被认为是由神经降压素受体亚型1(NTS1)和神经降压素受体亚型2(NTS2)共同介导的。NT及其受体广泛分布于中枢神经系统的痛觉环路。因此，NT可能对痛觉通路的许多结构进行调制，如脊髓、延髓旋转腹侧(RVM)和中脑导水管周围灰质(PAG)。鞘内应用NT，或直接将NT注入RVM或PAG，或侧脑室注射NT均有镇痛作用。在急性疼痛和慢性疼痛模型中，NT均具有抗伤害性作用。NT的镇痛作用最初是在急性疼痛实验中发现的。在病理性疼痛中，如福尔马林注射引起的炎症性疼痛和坐骨神经压迫引起的神经病理性疼痛，NT也具有抗伤害作用。对躯体疼痛和由伤害性结直肠扩张(CRD)或扭体试验引起的内脏痛也有影响。值得注意的是，NT在应激诱导的伤害性感受(SIAN)中起着重要作用，特别是在高强度的应激实验中。然而，作为一种神经肽，NT容易被肽酶降解，不能通过血脑屏障。人们一直在努力寻找生物稳定性更好的NT类似物，并通过系统给药来抑制疼痛。本文综述了NT及其类似物在疼痛，特别是慢性疼痛模型中的镇痛作用及其机制。
Neurotensin (NT) is an endogenous 13 amino acid neuropeptide with profound opioid-independent analgesic effects. This role of NT is thought to be mediated by both neurotensin receptor subtype 1 (NTS1) and neurotensin receptor subtype 2 (NTS2). NT and its receptors are widely distributed in the pain circuits in central nervous system. Thus NT might modulate pain in many structures of pain pathway, such as spinal cord, rostroventral medulla (RVM) and periaqueductal gray (PAG). Actually either intrathecal application of NT or direct injection of NT into RVM or PAG or intracerebroventricular injection of NT showed analgesic effects. NT exerted its antinociceptive effects in both acute pain and chronic pain models. The analgesic effects of NT were originally found in acute pain experiments. In the case of pathological pain, for example, formalin injection induced inflammatory pain and sciatic nerve constriction induced neuropathic pain, NT also shows antinociceptive effects. The effects exist in somatic pain as well as visceral pain induced by noxious colorectal distension (CRD) or writhing test. It should be noted that NT plays an important role in stress-induced antinociception (SIAN), especially in higher intensity stress experiments. However as a neuropeptide, NT is susceptible to degradation by peptidases and cannot cross the blood-brain barrier (BBB). Great efforts have been made to find NT analogues that are more biologically stable and could inhibit pain by systematic administration. The present review focuses on the analgesic role and the underlying mechanisms of NT and its analogues in pain, especially in chronic pain models.