Upregulation of tumor necrosis factor-alpha in nucleus accumbens attenuates morphine-induced rewarding in a neuropathic pain model
Upregulation of tumor necrosis factor-alpha in nucleus accumbens attenuates morphine-induced rewarding in a neuropathic pain model
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伏隔核中肿瘤坏死因子-α 的上调减弱了神经病理性疼痛模型中吗啡诱导的奖赏
DOI：
10.1016/j.bbrc.2014.05.025
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发表时间：
2014
影响因子：
3.1
通讯作者：
Liu Xianguo
中科院分区：
文献类型：
--
作者：
Wu Ying;Na Xiaodong;Zang Ying;Cui Yu;Xin Wenjun;Pang Ruiping;Zhou Lijun;Wei Xuhong;Li Yongyong;Liu Xianguo
用阿片类镇痛药治疗神经性疼痛仍然存在争议，主要问题是成瘾的风险。在这里，我们使用大鼠和小鼠神经性疼痛的保留神经损伤（SNI）模型来研究这个问题。SNI可抑制低剂量（3.5 mg/kg）吗啡（莫尔）诱导的条件性位置偏爱（CPP），对痛觉超敏有效，但对高剂量（15.0 mg/kg）莫尔无作用。SNI后，髓核（NAcc）中的肿瘤坏死因子-α（TNF-α）上调。SNI对MOR诱导的CPP的抑制作用可被TNF受体1（TNFR 1）基因缺失或NAcc内注射抗TNF-α阻断，并可被假手术大鼠NAcc内注射TNF-α模拟。此外，SNI还可降低NAcc内多巴胺（DA）水平，上调多巴胺转运体（DAT），但对腹侧被盖区（VTA）内总酪氨酸羟化酶（TH）和磷酸化TH（p-TH）无明显影响。因此，DA再摄取的增加而不是其合成的减少可能导致DA水平的降低。最后，SNI动物的NAcc中DAT的上调再次被TNFR 1的基因缺失或抗TNF-α的NAcc注射阻断，并且在假手术动物中通过NAcc注射TNF-α来模拟。因此，我们的数据提供了新的证据表明，在神经病理性疼痛条件下，NAcc中TNF-α的上调可能通过上调NAcc中DAT来减弱MOR诱导的奖励。
Treatment of neuropathic pain with opioid analgesics remains controversial and a major concern is the risk of addiction. Here, we investigated this issue with spared nerve injury (SNI) model of neuropathic pain in rats and mice. SNI prevented conditioned place preference (CPP) induced by low dose (3.5 mg/kg) of morphine (MOR), which was effective for anti-allodynia, but not by high dose (⩾5.0 mg/kg) of MOR. Tumor necrosis factor-alpha (TNF-α) was upregulated in nucleus accumbens (NAcc) following SNI. The inhibitory effect of SNI on MOR-induced CPP was blocked by either genetic deletion of TNF receptor 1 (TNFR1) or microinjection of anti-TNF-α into the NAcc and was mimicked by intra-NAcc injection of TNF-α in sham rats. Furthermore, SNI reduced dopamine (DA) level and upregulated dopamine transporter (DAT) in the NAcc, but did not affect total tyrosine hydroxylase (TH) or phospho-TH (p-TH), a rate-limiting enzyme of catecholamine biosynthesis, in ventral tegmental area (VTA). Accordingly, the increase in DA reuptake but not decrease in its synthesis may lead to the reduction of DA level. Finally, the upregulation of DAT in the NAcc of SNI animals was again blocked by either genetic deletion of TNFR1 or NAcc injection of anti-TNF-α, and was mimicked by NAcc injection of TNF-α in sham animals. Thus, our data provided novel evidence that upregulation of TNF-α in NAcc may attenuate MOR-induced rewarding by upregulation of DAT in NAcc under neuropathic pain condition.