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中脑导水管周围灰质电刺激与丘脑电刺激对大鼠伤害感知行为的差异调节

王宁, 张婷, 苏园林, 王锦琰, 罗非

中国科学院心理研究所，心理健康院重点实验室，北京 100101；温州医科大学应用心理学系，温州 325035

摘要

深部脑刺激是一种广泛用于治疗中枢神经及精神疾病的功能型手术疗法。深部脑刺激在临床应用于疼痛治疗起源于半个多世纪以前，能够有效治疗多种类型的顽固疼痛，然而其作用机制尚不清楚。为了进一步探索其神经机制，首先需要建立合适的深部脑刺激治疗疼痛的动物模型。本研究在大鼠的中脑导水管周围灰质腹外侧区(ventrolateral periaqueductal gray, vlPAG)或丘脑腹后外侧核(ventral posterior lateral nucleus, VPL)埋置刺激电极，研究深部脑刺激对正常大鼠急性痛、完全弗式佐剂(complete Freund’s adjuvant, CFA)注射引起的慢性炎症痛大鼠模型以及脊神经结扎 (spinal nerve ligation, SNL)手术引起神经病理痛大鼠模型的镇痛效果。主要结果如下：(1)在正常大鼠中，单侧vlPAG刺激能够显著提高双侧足底的热辐射痛阈，即产生显著的双侧镇痛作用；(2)在CFA建立的慢性炎症痛模型中，对侧vlPAG刺激和VPL刺激都能够显著提高CFA侧足底的热辐射痛阈，即产生显著的镇痛作用；(3)在SNL手术引发的慢性神经源性痛模型中，对侧VPL刺激能够显著提高SNL侧足底的机械痛阈，而vlPAG刺激对SNL引发的触诱发痛没有影响。以上结果提示，PAG刺激对于急性痛以及慢性炎症痛有着较好的镇痛效果，而VPL刺激更适合慢性炎症痛和慢性神经病理痛的镇痛研究。

关键词： 深部脑刺激; 慢性炎症痛; 神经病理痛; 镇痛

分类号：Q424

Differential modulation of electrical stimulation of periaqueductal gray and thalamus on nociceptive behaviors of rats

WANG Ning, ZHANG Ting, SU Yuan-Lin, WANG Jin-Yan, LUO Fei

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China； Department of Applied Psychology, Wenzhou Medical University, Wenzhou 325035, China

Abstract

Deep brain stimulation (DBS) is a surgical treatment which has shown remarkable therapeutic benefits for patients with a variety of neurologic conditions. As an important application, DBS has been used to treat intractable pain for over 60 years. Clinical studies have revealed that the selection of the stimulation sites depended on the types of pain. In this study, we selected ventrolateral periaqueductal gray (vlPAG) and ventral posterior lateral nucleus (VPL) as the target brain areas, which were widely used in clinical treatment of refractory pain, to clarify and compare the effects of vlPAG and VPL stimulation on different models of pain. Acute pain was evoked by thermal stimulation. The chronic inflammatory pain was produced by complete Freund’s adjuvant (CFA) injection, while neuropathic pain was induced by spinal nerve ligation (SNL) surgery. Some important results emerged from this study: (1) in the experiment of normal rats, we found that unilateral vlPAG stimulation could lead to a significant increase of the thermal withdrawal threshold in bilateral hindpaws of rats, which means a significant bilateral analgesic action; (2) in the CFA test, both contralateral vlPAG and VPL stimulation significantly alleviated the thermal hyperalgesia, which exhibited analgesic effects to the chronic inflammatory pain; (3) in the SNL experiment, the results revealed that contralateral VPL stimulation could significantly abolish the mechanical allodynia induced by SNL, indicating remarkable analgesic effect to neuropathic pain. But the vlPAG stimulation did not have any effect on the mechanical allodynia. These results suggest that the electrical stimulation of the PAG works more effectively on nociceptive pain, including acute pain and chronic inflammatory pain. Besides, the VPL stimulation is much more sensitive for chronic pain, including chronic inflammatory pain and neuropathic pain.

Key words: deep brain stimulation; chronic inflammatory pain; neuropathic pain; analgesia

收稿日期：2015-10-19　　录用日期：2016-02-24

通讯作者：罗非　　E-mail: luof@psych.ac.cn

引用本文：

王宁, 张婷, 苏园林, 王锦琰, 罗非. 中脑导水管周围灰质电刺激与丘脑电刺激对大鼠伤害感知行为的差异调节[J]. 生理学报 2016; 68 (2): 115-125.

WANG Ning, ZHANG Ting, SU Yuan-Lin, WANG Jin-Yan, LUO Fei. Differential modulation of electrical stimulation of periaqueductal gray and thalamus on nociceptive behaviors of rats. Acta Physiol Sin 2016; 68 (2): 115-125 (in Chinese with English abstract).