功能磁共振脑连接度中心性对精神分裂症症状的预测评估

精神分裂症是一种严重影响患者身心健康的精神类疾病,绝大部分患者需要终身服药以控制症状,因此药物疗效的评估预测对于患者治疗方法的选择十分重要。采用功能磁共振的脑连接度中心度(DC)指标,分析临床常用抗精神病药物利培酮和氯氮平对大脑功能的影响,并尝试建立预测评估两种药物疗效的方法。基于44例精神分裂症患者(20例利培酮治疗组、24例氯氮平治疗组)和30例健康志愿者的脑静息态功能磁共振成像数据,首先采用方差分析得到患者组与正常组间的差异脑区,然后根据这些脑区的DC值,用多变量支持向量回归算法构建回归模型,探讨用DC值评测患者症状的可行性。结果发现,两个患者组的丘脑、脑岛及初级感知运动相关皮层的功能连接特征存在显著的异常(P< 0.05),且可以有效地预测氯氮平组患者的阴性症状(r=0.448, P<0.05),但未能较好地预测利培酮患者的症状。在统计对比分析的基础上,利用回归模型,标识出抗精神疾病药物作用的部分重要脑区,因而有助于将来患者治疗的药物选择。     

基于功能连接算法的斜视性弱视儿童静息态功能磁共振成像的研究

目的探索斜视性弱视儿童脑功能区及其功能连接的改变,揭示斜视性弱视的发生与脑功能改变的相关性。方法在静息态下采集22位斜视性弱视儿童和10名健康儿童脑功能磁共振图像,利用DPARSF软件计算全脑与ROI功能区的连接系数,并应用t检验对实验组和健康对照组进行组内和组间功能连接系数分析。结果发现斜视性弱视儿童部分脑功能连接低于正常对照组的相应脑区连接,这些功能区主要分布于枕叶、颞叶、小脑后叶、顶叶、额叶、扣带回等脑区。结论基于静息态的f MRI的脑功能连接算法可以反映斜视性弱视儿童视皮层的变化和多脑区神经活动的变化。     

吸烟成瘾者戒烟前后的静息态功能磁共振研究

为了发现吸烟成瘾者在戒烟前后的脑功能特征改变,探索戒烟过程的神经生理理论基础,14名吸烟成瘾者同意戒烟并完成了试验,另外11名健康不吸烟的志愿者参与了对照试验。采取两因素混合实验设计方法,以静息态功能磁共振影像技术为技术手段,利用区域一致性算法来研究吸烟成瘾者在戒烟前后的神经活动及其与正常人之间的差异,并对这些差异进行组内与组间交互分析。戒烟两周后,在补充运动区、中央旁小叶、距状裂周围皮层、楔叶和舌回等区域的Re Ho值明显上升,意味着在这些脑区的神经活动同步性增强,而在楔前叶和后扣带回脑区同步性降低。在补充运动区、中央旁小叶、中央前回、中央后回、眶部额上回等脑区存在组间交叉效应。本研究结果显示吸烟成瘾者戒烟2周后在补充运动区的功能显著增强。     

基于低频振幅算法的屈光参差性弱视自发脑活动研究

目的基于低频振幅(amplitude of low frequency fluctuation,ALFF)算法分析屈光参差性弱视和正常对照组的功能性磁共振成像(functional magnetic resonance imaging,f MRI)图像数据,对比揭示弱视患者脑部自发活动的异常,以及这些异常与弱视视力损失的相关性。方法在闭眼静息条件下采集22例弱视成年人和21例正常对照组f MRI数据,对f MRI数据进行预处理,计算每个被试脑区的ALFF值。应用双样本t检验对ALFF结果进行组间分析,采用皮尔森分析弱视不同脑区的ALFF与其损伤的相关程度。结果在屈光参差性成人弱视与正常组有显著性差异的脑区中,脑部自发活动增加的脑区主要分布在颞下回、颞上回、枕叶等区域,脑部自发活动降低的脑区主要分别在小脑后叶、额下回、额上回等区域。首次发现小脑后叶、楔回、枕叶、颞上回和额叶等区域脑区自发活动与弱视损伤有显著相关性。结论基于低频振幅的静息态磁共振分析是有效的非侵入式脑区同步性异常研究方法,能够反映屈光参差性弱视自发脑部活动脑区异常表现,这些同步性异常表现与视力损失程度有较强的相关性,这些结果对于弱视致病机制模型研究和提出新的治疗方法都有重要启发。     

小胶质细胞在VPA孤独症模型大鼠脑增龄过程中的变化

目的:检测小胶质细胞在孤独症发病相关脑区的活化改变,探讨小胶质细胞在孤独症发病中的作用。方法:免疫组织化学技术检测丙戊酸盐(valproic acid sodium salt,VPA)孕鼠注射法建立的子代孤独症模型大鼠脑内小胶质细胞在不同周龄时前额叶皮层,海马及小脑中的活化改变;Western Blot检测小胶质细胞内电离钙绑定衔接分子-1(ionized calcium binding adaptor molecule-1,Iba-1)的表达。结果:小胶质细胞免疫组化染色显示:与正常组相比,VPA模型组大鼠不同脑区小胶质细胞的数量和密度增多,胞体增大、突起的长度和直径均增加,表明小胶质细胞的活化现象明显。Western Blot检测显示:孤独症VPA模型组前额叶皮层、海马、小脑内Iba-1的表达不同程度高于正常对照组(P0.05),同样印证小胶质细胞在VPA模型组大鼠不同脑区的活化改变。结论:小胶质细胞的活化改变广泛存在于孤独症大鼠脑内,这可能是导致孤独症脑神经元发育与连结异常及脑内神经炎症病理过程的部分原因。     

神经病理痛模型大鼠前扣带皮层不同水平磷酸化细胞外信号调节激酶表达差异比较

目的探讨痛相关情绪模型大鼠前扣带皮层(ACC)磷酸化细胞外信号调节激酶(p-ERK)的分布特点。方法将12只雄性SD大鼠随机分为对照组和模型组。模型组大鼠进行右侧腰5脊神经结扎制做模型。采用右后足跖机械痛阈检测观察行为变化,旷场实验和高架O迷宫实验检测痛相关情绪变化,免疫荧光技术检测同侧前扣带皮层前囟前3.2、2.7及2.2mm 3个水平p-ERK表达。结果大鼠经神经病理痛模型制做成功后机械痛阈显著下降,焦虑样行为产生。前扣带皮层前囟前3.2、2.7及2.2mm水平p-ERK阳性细胞表达量分别为11.89±2.57、32±4.67和17.56±2.04。对照组相应的p-ERK阳性细胞表达量分别为12.44±2.16、10±0.87和10.11±1.36。除前囟前3.2mm水平对照组与模型组相比没有显著性差异(P0.05)之外,其他两个水平p-ERK阳性细胞表达量模型组显著高于对照组(P0.01)。结论神经病理性疼痛能诱发大鼠焦虑情绪的产生及ACC脑区pERK的表达增高,这种变化可能主要与ACC脑区前囟前2.7及2.2mm水平p-ERK的变化相关,而与前囟前3.2mm水平无关。     

糖尿病视网膜病变患者自发活动性异常的脑区与MoCA的相关性研究

目的 基于静息态功能磁共振局部一致性技术探讨糖尿病视网膜病变患者局部脑区一致性的改变及与认知关系.方法 选择27例糖尿病视网膜病变(DR)及与之年龄、性别、受教育年限相匹配的单纯糖尿病(N-DR)患者27例,均进行实验室检查、蒙特利尔量表(MoCA)检测及头颅磁共振扫描.利用多元回归分析及Pearson回归分析观察临床变量与活动性异常活动脑区ReHo值之间的关系.结果 相对于N-DR,DR患者在左小脑后叶、右额叶/额中回/内侧回、右枕叶/楔叶/距状回、左颞叶/上/中回、右边缘叶/后扣带回、左顶叶/中央后回ReHo值降低;在左额叶/眶部额上回、左顶叶/楔前叶ReHo值增强.而且MoCA量表评分与颞叶及楔前叶异常活动的脑区存在相关性.降低的枕叶距状回及颞叶中回与糖化血红蛋白呈负相关,增强的眶额叶与糖化血红蛋白呈正相关.结论 糖尿病视网膜病变患者存在多个脑区活动性异常的表现,且这些局部异常活动的脑区与认知功能及糖化血红蛋白存在相关.     

基于独立成分分析和时间相关分析的脑功能连通研究方法[英文]

目的:利用静息状态功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,提出联合独立成分分析(independent component analysis,ICA)和时间相关分析的人脑功能连通性研究方法。方法:首先采用空间ICA定位任务激活的脑区;然后选择一个激活区作为感兴趣区域(region of interest,ROI),采用时间相关分析方法检测静息状态大脑特定皮层的功能连通性,并通过检测人脑运动皮层的功能连通性验证方法的有效性。结果:大脑运动皮层功能连通网络包括初级运动区、辅助运动区、初级感觉皮层、背侧前运动区和后顶骨体觉区。实验结果表明,静息状态下,时间相关分析检测到的运动皮层的功能连通网络与已知的解剖连通相一致。结论:利用静息fMRI,结合空间ICA和时间相关分析方法,检测了静息时人脑运动皮层的功能连通网络,为脑区间功能连通的研究提供了一种简便的、无损的、有效的研究方法。     

2型糖尿病患者异常活动脑区的改变

目的 应用静息态脑功能技术观察2型糖尿病患者脑区活动性的异常改变.方法 选择24例符合2型糖尿病诊断标准的患者为糖尿病组,与之匹配的24例健康志愿者为对照组,均进行头颅MR扫描,将采集的临床资料及提取活动性异常脑区进行多元回归分析.结果 2型糖尿病患者组相对于对照组存在多个异常的脑区活动ALFF值降低的脑区在颞叶、左扣带回、左小脑,增强的脑区位于右额叶、左海马、双侧楔叶.楔叶及颞叶改变与糖化血红蛋白存在相关性,楔叶与餐后血糖存在正相关.结论 2型糖尿病患者在尚未出现并发症阶段即出现脑区异常的改变,及早发现脑部病变对于临床早期发现及诊治具有积极意义.     

基于ReHo方法的大学生网络成瘾静息功能磁共振成像研究

目的:探讨网络成瘾大学生静息状态脑功能特点。方法:采用ReHo分析方法 ,19名网络成瘾大学生及19名对照进行磁共振脑功能成像,比较两组平均脑ReHo图的差异。结果:IAD组ReHo值升高区域主要集中在小脑、脑干、扣带回(右侧)、双侧海马旁回、右侧额叶(直回,额中回及额下回)、左侧额上回、左侧楔前叶、右侧中央后回、右侧枕中回、右侧颞下回、左侧颞上回及颞中回;ReHo降低的区域仅表现在左侧顶叶的楔前叶。结论:网络成瘾大学生局域一致性存在异常,大部分脑区同步性增强,小脑、脑干、边缘叶、额顶叶同步性增强可能与网络成瘾奖赏通路有关。     

Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats

Both myelinated and unmyelinated afferents are implicated in transmitting diabetic neuropathic pain. Although unmyelinated afferents are generally considered to play a significant role in diabetic neuropathic pain, pathological changes in diabetic neuropathy occur mostly in myelinated A-fibers. In the present study, we first examined the role of capsaicin-sensitive C-fibers in the development of allodynia induced by diabetic neuropathy. We then studied the functional changes of afferent nerves pertinent to diabetic neuropathic pain. Diabetes was induced in rats by i.p. streptozotocin. To deplete capsaicin-sensitive C-fibers, rats were treated with i.p. resiniferatoxin (300 microg/kg). Mechanical and thermal sensitivities were measured using von Frey filaments and a radiant heat stimulus. Single-unit activity of afferents was recorded from the tibial nerve. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic rats. Resiniferatoxin treatment did not alter significantly the degree and time course of allodynia. Post-treatment with resiniferatoxin also failed to attenuate allodynia in diabetic rats. The electrophysiological recordings revealed ectopic discharges and a higher spontaneous activity mainly in Adelta- and Abeta-fiber afferents in diabetic rats regardless of resiniferatoxin treatment. Furthermore, these afferent fibers had a lower threshold for activation and augmented responses to mechanical stimuli. Thus, our study suggests that capsaicin-sensitive C-fiber afferents are not required in the development of allodynia in this rat model of diabetes. Our electrophysiological data provide substantial new evidence that the abnormal sensory input from Adelta- and Abeta-fiber afferents may play an important role in diabetic neuropathic pain.     

p-ERK1/2-AP-1通路在姜黄素抗大鼠糖尿病神经病理性痛中的作用

目的: 观察p-ERK1/2-AP-1通路在姜黄素(Cur)抗大鼠糖尿病神经病理性痛(DNP)中的作用。方法: 雄性SD大鼠96只,随机分为4组(n=24):正常对照组、DNP组、DNP+溶剂组(DNP+Sol组)和DNP+Cur 100 mg/kg组(DNP+Cur组)。除正常对照组外,其余各组采用腹腔注射链唑霉素75 mg/kg的方法制备DNP模型,造模成功后每天1次腹腔注射相应的溶剂或Cur,持续2周。于造模前2 d、造模后14 d、腹腔给药后3、7、14 d时测定机械缩足痛阈(MWT)、热缩足潜伏期(TWL)和非空腹尾静脉血糖值,取脊髓腰膨大及L₄/L₅背根神经节(DRG),采用免疫组化及Western blotting法测定脊髓背角和DRG p-ERK1/2的表达,电泳迁移率变动分析AP-1的表达。结果: 与正常对照组相比,DNP组各时点MWT降低、TWL缩短;血糖值升高;脊髓背角及DRG p-ERK1/2均出现表达上调(P<0.05);脊髓背角AP-1表达上调(P<0.05)。与DNP组相比,DNP+Cur组在给药后7 d MWT回升、TWL延长;在给药后14 d脊髓背角及DRG p-ERK1/2、脊髓背角AP-1表达下调(P<0.05),但并不影响血糖水平。结论: Cur可减轻大鼠糖尿病神经病理性痛,其机制可能与抑制脊髓背角和DRG神经元p-ERK1/2-AP-1通路激活有关。     

Curcumin Attenuates Diabetic Neuropathic Pain by Downregulating TNF-α in a Rat Model

The mechanisms involved in diabetic neuropathic pain are complex and involve peripheral and central pathophysiological phenomena. Proinflammatory tumour necrosis factor α (TNF-α) and TNF-α receptor 1, which are markers of inflammation, contribute to neuropathic pain. The purpose of this experimental study was to evaluate the effect of curcumin on diabetic pain in rats. We tested 24 rats with diabetes induced by a single intraperitoneal injection of streptozotocin and 24 healthy control rats. Twelve rats in each group received 60 mg/kg oral curcumin daily for 28 days, and the other 12 received vehicle. On days 7, 14, 21, and 28, we tested mechanical allodynia with von Frey hairs and thermal hyperalgesia with radiant heat. Markers of inflammation in the spinal cord dorsal horn on day 28 were estimated with a commercial assay and Western blot analysis. Compared to control rats, diabetic rats exhibited increased mean plasma glucose concentration, decreased mean body weight, and significant pain hypersensitivity, as evidenced by decreased paw withdrawal threshold to von Frey hairs and decreased paw withdrawal latency to heat. Curcumin significantly attenuated the diabetes-induced allodynia and hyperalgesia and reduced the expression of both TNF-α and TNF-α receptor 1. Curcumin seems to relieve diabetic hyperalgesia, possibly through an inhibitory action on TNF-α and TNF-α receptor 1.     

Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats

Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for >/=7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.     

Does the Tibial and Sural Nerve Transection Model Represent Sympathetically Independent Pain?

Neuropathic pain can be divided into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Rats with tibial and sural nerve transection (TST) produce neuropathic pain behaviors, including spontaneous pain, tactile allodynia, and cold allodynia. The present study was undertaken to examine whether rats with TST would represent SMP- or SIP-dominant neuropathic pain by lumbar surgical sympathectomy. The TST model was generated by transecting the tibial and sural nerves, leaving the common peroneal nerve intact. Animals were divided into the sympathectomy group and the sham group. For the sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6 one week after nerve transection. The success of the sympathectomy was verified by measuring skin temperature on the hind paw and by infra red thermography. Tactile allodynia was assessed using von Frey filaments, and cold allodynia was assessed using acetone drops. A majority of the rats exhibited withdrawal behaviors in response to tactile and cold stimulations after nerve stimulation. Neither tactile allodynia nor cold allodynia improved after successful sympathectomy, and there were no differences in the threshold of tactile and cold allodynia between the sympathectomy and sham groups. Tactile allodynia and cold allodynia in the neuropathic pain model of TST are not dependent on the sympathetic nervous system, and this model can be used to investigate SIP syndromes.     

内质网应激蛋白BiP在姜黄素抗2型糖尿病神经病理性疼痛大鼠的作用

目的: 探讨姜黄素对2型糖尿病诱导的神经病理性疼痛(DNP)大鼠机械痛敏(MWT)、热痛敏(TWL)、脊髓背角和背根神经节(DRG)的保护作用及机制。方法: 高脂高糖饲料喂养8周诱导胰岛素抵抗后,继以单次小剂量链脲佐菌素(STZ)35 mg/kg腹腔注射,在注射STZ前和14 d后采用Electronic Von Fery触觉测痛仪和甩尾/足底测试仪测大鼠MWT和TWL,注射STZ 3 d后血糖≥16.7 mmol/L且在注射STZ 14 d后痛阈下降至基础值85%以下者入选为D组(81只)。将D组随机分为3组(n=27): DNP组、DNP+姜黄素100 mg·kg^-1·d^-1组(DCur组)和DNP+溶剂组(DSC组),另取27只为正常对照组(C组),给予普通饲料喂养。给姜黄素3、7、14 d后测血糖、MWT与TWL,并在同时点取大鼠L4~L6脊髓和DRG,用免疫组化和免疫印迹法测定脊髓背角和DRG中免疫球蛋白重链结合蛋白(BiP)的表达。结果: 与C组相比,DNP组各时点MWT降低,TWL缩短,血糖值升高,脊髓背角和DRG中BiP均出现表达上调(P<0.05)。与DNP组相比,DCur组在给姜黄素7 d后MWT升高,TWL延长;给姜黄素14 d后脊髓背角和DRG中BiP表达下调(P<0.05)。DSC组和DNP组相比差异无统计学意义。结论: BiP参与了2型糖尿病神经病理性疼痛的发病机制。姜黄素减轻2型糖尿病大鼠神经病理性疼痛的机制可能与抑制BiP表达有关。     

Streptozotocin-induced diabetic hyperalgesia in rats is associated with upregulation of toll-like receptor 4 expression

Neuropathic pain is one of the common complications of diabetes mellitus, and current treatments often do not meet medical needs. Toll-like receptor 4 (TLR4) has been implicated as a potential therapeutic target in neuropathic and other pain models. In this study, we investigated whether TLR4 expression in spinal cord would be altered in streptozotocin-induced diabetic rat model, which had persistent mechanical and thermal hypersensitivity. The results showed that the mRNA expression of TLR4 was upregulated in streptozotocin-treated animals. Furthermore, TLR4 expression was associated with both paw-pressure withdrawal threshold toward mechanical stimulus and paw withdrawal latency toward thermal stimulus. The protein levels of TNF-α and IL-1β, two downstream proinflammatory cytokines of TLR4 signaling pathway, were also significantly raised and correlated with mechanical/thermal hypersensitivity in diabetic rats. Together, these data have demonstrated that TLR4 and its signaling pathway are associated with neuropathic pain in a diabetic model. It may imply that TLR4 could be a novel target for treating diabetic neuropathy.     

基于静息态功能磁共振形态学腰椎间盘突出症慢性下肢痛模型大鼠的实验研究

【摘要】目的:基于静息态功能磁共振（RS-fMRI）技术和疼痛行为学技术，观察腰椎间盘突出症（LDH）慢性下肢痛模型大鼠脑结构及功能改变的特点，揭示LDH慢性下肢痛的脑机制。方法:选用6~8周龄健康的SD雄性大鼠24只，体质量（250±20） g，采用随机数字表法分为3组:正常组、假手术组、模型组，模型组采用自体髓核移植法建立LDH慢性下肢痛大鼠模型。各组分别于建模前0天、建模后第2、7、14、21、28天进行大体行为学观察、机械痛阈值测定、热痛阈值测定。每组随机选取4只大鼠分别于建模前0天、建模后第14、28天，利用Bruker公司7.0T核磁收集BOLD数据，采用局部一致性（ReHo）、分数低频振幅（fALFF）方法处理BOLD数据，对所得数据进行统计学分析。结果:（1）3组大鼠建模前机械缩足反射阈值（PWT）和热缩足反射潜伏期（TWL）比较差异无统计学意义（P>0.05）；假手术组建模后各时间点PWT和TWL与正常组比较，差异无统计学意义（P>0.05）；模型组大鼠建模后各时间点PWT和TWL与正常组、假手术组比较，差异有统计学意义（P<0.05）。（2）3组大鼠不同时间点脑结构区域比较存在交互作用，差异有统计学意义（P<0.05）。脑区图结果显示ReHo值存在显著差异的脑区有:左室周灰质、右纹状体；fALFF值存在显著差异的脑区有:右纹状体、左嗅球、双侧小脑分子层。结论:（1）大鼠采用自体髓核移植法进行LDH建模后，机械痛阈值和热痛阈值明显降低，出现痛觉过敏反应，提示LDH慢性下肢痛大鼠建模成功；（2）LDH慢性下肢痛模型大鼠静息态下某些脑区功能活动有明显改变，可能与慢性疼痛的发生和维持有关。     

Expression of IL-1beta in supraspinal brain regions in rats with neuropathic pain

We examined mRNA expression of the pro-inflammatory cytokine IL-1beta in the brainstem, thalamus, and prefrontal cortex in two rat models of neuropathic pain. Rats received a neuropathic injury: spared nerve injury (SNI) or chronic constriction injury (CCI), sham injury, or were minimally handled (control). Neuropathic pain-like behavior was monitored by tracking tactile thresholds. SNI-injured animals showed a robust decrease in tactile thresholds of the injured foot, while CCI-injured animals did not show tactile threshold changes. Ten or 24 days after nerve injury, IL-1beta gene expression in the brain was determined by RT-PCR. IL-1beta expression changes were observed mainly at 10 days after injury in the SNI animals, contralateral to the injury side, with increased expression in the brainstem and prefrontal cortex. The results indicate that neuro-immune activation in neuropathic pain conditions includes supraspinal brain regions, suggesting cytokine modulation of supraspinal circuitry of pain in neuropathic conditions.     

Periaqueductal gray stimulation suppresses spontaneous pain behavior in rats

Methods for evaluating analgesic effect for spontaneous pain are increasingly important because it is reported by most patients with neuropathic pain. The present study assessed the analgesic effects of periaqueductal gray (PAG) stimulation in the spared nerve injury (SNI) model of neuropathic pain of the rat. Spontaneous rapid paw withdrawal movements were used as the index of spontaneous pain. Deep-brain stimulation in the PAG was performed in rats 3 weeks after SNI. Significant analgesic effects on spontaneous pain behavior were observed at the same stimulation parameter that reversed the reduced mechanical threshold of the von Frey test. Both analgesic effects lasted 30-40min beyond the 3min stimulation period. In summary, PAG stimulation was effective in alleviating spontaneous pain and mechanical allodynia in the SNI rat. The frequency of spontaneous paw lifting, a behavioral index of spontaneous pain used in this study, will be useful for future testing of therapeutic methods.