痛抑郁二联征模型大鼠中缝背核不同水平5羟色胺表达差异

目的 探讨痛抑郁二联征模型大鼠中缝背核（DRN）5羟色胺（5-HT）阳性细胞的分布特点。 方法 20只雄性SD大鼠随机分为对照组和模型组。模型组大鼠连续3d皮下注射利血平,每日1次,以诱发痛抑郁二联征模型。模型制作后第1天和第2天检测左后足机械缩足阈观察大鼠痛阈变化,模型制作后第2天旷场实验和高架O迷宫实验检测大鼠情绪变化,免疫荧光技术观察DRN前囟后6.8mm、7.3mm和7.8mm水平的5-HT表达。 结果 模型组大鼠经利血平注射后机械痛阈显著下降,并产生抑郁样行为。对照组的DRN前囟后6.8mm、7.3mm和7.8mm水平的5-HT阳性细胞表达量分别为106.00±10.21、96.67±24.50和195.67±2.33。模型组相应的表达量分别为61.67±14.53,72.33±34.35和53.67±26.77。除前囟后7.8mm水平模型组与对照组相比有显著性差异（P<0.05）之外,其他两个水平5-HT阳性细胞表达量模型组和对照组之间差异无显著性（P>0.05）。 结论 利血平诱导的痛抑郁二联征大鼠模型以及中缝背核5-HT表达的降低,可能主要与DRN前囟后7.8mm水平的5-HT阳性细胞数变化有关,而与前囟后6.8mm和后7.3mm 水平无关。     

糖尿病神经病理性疼痛大鼠脑异常活动的功能磁共振研究

目的　构建糖尿病神经病理性疼痛大鼠模型,利用功能磁共振成像技术,观察脑功能活动变化情况,探索异常功能活动的脑区。 方法　雄性SD大鼠48只,随机分为糖尿病组（n=36）和对照组（n=12）。糖尿病组通过腹腔注射60 mg/kg链脲佐菌素构建糖尿病模型,同时测定50％机械刺激缩足反射阈值的变化情况,根据触觉诱发性疼痛标准,糖尿病组大鼠被分成疼痛组及无痛组。利用锰离子增强功能磁共振成像技术进行大鼠脑功能成像,图像后处理分析糖尿病神经病理性疼痛大鼠脑内异常功能活动区域。 结果　成功构建糖尿病神经病理性疼痛大鼠模型,发现脑内存在显著性功能活动增强的区域,包括感觉皮层、腹内侧前额叶皮层、前扣带皮层、下橄榄核、梨状皮层、杏仁核及岛叶部分皮层。 结论　糖尿病神经病理性疼痛大鼠脑内部分脑区具有异常功能活动的表现,这些脑区很有可能参与该疼痛调控的中枢机制。     

前扣带回TRPC1/4/5通道在小鼠慢性炎性痛所致焦虑样行为中的作用

目的:探讨前扣带回(ACC)中瞬时感受器电位通道1/4/5(TRPC1/4/5)在小鼠慢性炎性痛诱发焦虑样行为过程中的表达变化。方法:将雄性C57/BL6小鼠(n=30)随机分为3组:正常对照组(Control组)、CFA1 d组和CFA 7 d组,小鼠左后肢足底皮下注射完全弗氏佐剂(CFA)建立慢性炎性痛模型。采用小鼠机械痛和热痛敏方法检测痛阈变化,旷场和高架十字迷宫法检测小鼠焦虑样行为,real time RT-PCR和Western Blot方法检测TRPC1/4/5通道表达水平变化。结果:小鼠左后肢足底注射CFA后出现明显的机械性痛敏和热痛敏现象。旷场和高架十字迷宫实验显示CFA诱发炎性痛敏7 d后,小鼠在高架十字迷宫开臂进入次数和时间、旷场中央区活动距离均明显降低,提示慢性炎性痛后小鼠出现显著的焦虑样行为。采用real time RT-PCR和Western Blot实验,观察到炎性痛诱发焦虑样小鼠ACC脑区中TRPC1/4/5通道的mRNA和蛋白表达水平较正常组均出现显著上调。结论:CFA诱发的慢性炎性痛模型中,小鼠出现明显的焦虑样症状,同时ACC脑区的TRPC1/4/5通道表达水平显著升高,提示慢性炎性痛诱发的焦虑样行为可能与痛觉神经通路中ACC脑区的TRPC1/4/5通道蛋白表达有密切关系。     

N-甲基-D-天冬氨酸受体/MAPK/环磷腺苷效应元件结合蛋白通路在前扣带皮层介导痛相关情绪

目的 探讨N-甲基-D-天冬氨酸(NMDA)受体/MAPK/环磷腺苷效应元件结合蛋白(CREB)通路参与前扣带皮层介导痛相关情绪的机制。方法 选取健康SD大鼠共42只，随机分为空白对照组(Ctrl)、脚掌注射生理盐水(NS)组、脚掌注射完全弗氏佐剂(CFA)模型组(CFA)、脚掌注射CFA及前扣带皮层吻侧部(rACC)中注射NS组(CFA+NS)、脚掌注射NS及rACC中注射NS组(NS+NS)、脚掌注射CFA及rACC内注射NMDA受体拮抗剂(APⅤ)组(CFA+APⅤ)、脚掌注射NS及rACC内注射APⅤ组(NS+APⅤ),每组n=6只。分析大鼠回避分数及观察大鼠热缩足潜伏期(PWL),采用免疫组织化学染色检测脑rACC区NMDA受体表达；免疫荧光染色检测脑rACC区NMDA受体、磷酸化ERK(p-ERK)、磷酸化CREB(p-CREB)表达；尼氏染色观察脑rACC区尼氏小体数量；Western blotting检测rACC区NMDA受体、MAPK、CREB、ERK、p-ERK、p-CREB、突触小体相关蛋白25的相互作用蛋白30(SIP30)蛋白表达；Real-time PCR检...     

鞘内注射丹参酮ⅡA对神经病理性疼痛大鼠的镇痛作用

目的:研究丹参酮ⅡA对坐骨神经慢性压迫大鼠的的镇痛效果及大鼠脊髓背角内半胱氨酸天冬氨酸蛋白酶3(caspase-3)和胶质纤维酸性蛋白(GFAP)表达的影响.方法:检测大鼠在手术前及术后14d的机械痛阈和热痛阈;PCR及免疫组织化学分别检测大鼠脊髓背角内caspase-3和GFAP基因及蛋白的表达,TUNEL法检测脊髓背角内的细胞凋亡.结果:与假手术组比较,模型组大鼠的机械痛阈和热痛阈明显降低,caspase3和GFAP的表达均增多,凋亡染色阳性细胞数目也增多;与模型组比较,丹参酮ⅡA处理组大鼠的机械痛阈和热痛阈明显升高,脊髓背角内caspase-3和GFAP的表达均下降,凋亡染色阳性细胞数目也减少,差异均有统计学意义.结论:鞘内注射丹参酮ⅡA对坐骨神经慢性压迫模型大鼠有镇痛作用,其机制可能与降低脊髓背角内caspase-3和GFAP的表达有关.     

慢性炎性痛诱致小鼠焦虑样行为和前扣带回TRPC3和TRPC6通道的表达上调

目的:探讨慢性炎性痛诱致小鼠焦虑样行为情况下前扣带回(anterior cingulate cortex,ACC)TRPC 3/6通道的表达改变。方法:采用小鼠痛行为检测方法、旷场行为检测方法和免疫印迹实验(Western Blot)。结果:小鼠后肢足底皮下注射完全弗氏佐剂(complete freund’s adjuvant,CFA)建立慢性炎性痛模型。痛行为检测结果显示足底皮下注射CFA可以诱致小鼠产生长时程的机械性和热痛觉过敏现象。旷场实验可见CFA致炎致痛后的小鼠较正常小鼠在旷场中央区活动距离明显降低,停留时间明显减少,提示慢性炎性痛小鼠表现为显著的焦虑样行为。进一步采用Western Blot实验发现炎性痛焦虑样小鼠前扣带回脑区的TRPC3和TRPC6通道蛋白表达水平较对照组动物显著上调。结论:CFA引发的慢性炎性痛模型中,小鼠产生焦虑样情绪,TRPC3和TRPC6通道蛋白在ACC部位的蛋白表达水平明显升高。提示这些焦虑样痛情绪的发生与疼痛痛觉通路中ACC脑区的TRPC3及TRPC6表达密切相关。     

前扣带皮层中碱性成纤维细胞生长因子及其受体在慢性炎症性疼痛中的表达变化

目的 探讨完全弗氏佐剂（CFA）外周注射诱导的碱性成纤维细胞生长因子（FGF-2）及其受体在大脑前扣带皮层（ACC）中的表达变化。方法 单侧足底注射CFA 150μl诱导大鼠慢性炎症性疼痛,在不同时间点取前扣带皮层（每组3只动物）,通过RT-PCR和Western blotting方法分别检测FGF-2及其主要受体FGFR1-4 mRNA和FGF-2蛋白的表达变化。结果 大鼠单侧足底皮下注射CFA诱导了慢性炎症性疼痛。注射对侧脑区中,在注射后6 h、3 d、7 d、14 d,ACC中FGF-2和FGFR1的mRNA表达相对于正常组明显增加,FGFR2 mRNA在3 d、7 d、14 d表达增加。注射同侧脑区中,FGF-2和FGFR1mRNA的表达在注射CFA后6 h、3 d、7 d、14 d相对于正常组明显增加。双侧脑区的FGF-2蛋白表达在注射CFA后6 h、3 d和7 d明显增加。结论 CFA诱导的慢性炎症性疼痛状态下,FGF-2可能通过受体FGFR1参与疼痛在高级中枢部位的信号调节。     

阿利吉仑对慢性坐骨神经缩窄性损伤大鼠TNF-α表达的影响

目的探讨阿利吉仑对慢性坐骨神经缩窄性损伤(CCI)大鼠模型热痛阈和机械痛阈表达和肿瘤坏死因子-α(TNF-α)表达的影响。方法通过在坐骨神经上结扎四个松结制备实验CCI大鼠模型,大鼠随机分为正常组、CCI组和阿利吉仑组(50 mg/kg,腹腔注射)。造模后14 d检测各组热痛阈和机械痛阈,实时荧光定量PCR检测坐骨神经TNF-αmRNA表达。结果与正常组比较,模型组和阿利吉仑组热痛阈和机械痛阈显著降低,TNF-αmRNA表达水平显著增高(0.01)。与模型组比较,阿利吉仑组坐骨神经热痛阈、机械痛阈显著增高,TNF-αmRNA表达水平显著降低(0.01)。结论阿利吉仑上调坐骨神经缩窄性损伤大鼠坐骨神经热痛阈和机械痛阈可能与下调TNF-αmRNA表达相关。     

宫内感染后低龄大鼠脑组织中胶质纤维酸性蛋白的表达变化

目的:探讨胶质纤维酸性蛋白(GFAP)在宫内感染后低龄大鼠脑组织中的表达变化及其意义。方法: 对孕大鼠子宫内注入大肠杆菌建立宫内感染的大鼠模型,以子宫内注入生理盐水为对照组。两组分别于生后1、3、7、14及21 d取幼鼠脑组织,应用免疫组化方法检测脑组织中不同脑区GFAP的表达。结果: 生后1、3 d龄大鼠仅脑室旁白质区可见少许GFAP阳性细胞,两组细胞数无显著差异(P>0.05),其余脑区未见明显GFAP表达。感染组7日龄大鼠脑室旁白质和海马区GFAP阳性细胞数增多,与对照组比较差异显著(脑室旁白质区:9.73±3.55 vs 5.67±1.90,P<0.05;海马区:7.81±3.61 vs 2.16±1.11,P<0.05)。感染组14 d龄大鼠脑室旁白质、胼胝体及皮层区GFAP阳性细胞数增多,与对照组比较均有显著差异(脑室旁白质区:12.72±1.81 vs 9.00±0.93,P<0.01;胼胝体区:10.98±3.26 vs 4.44±1.15,P<0.01;皮层区:5.43±1.79 vs 2.71±0.67,P<0.01)。两组21 d龄大鼠各脑区GFAP阳性细胞数无显著差异(P>0.05)。结论: 宫内感染后低龄大鼠脑组织中GFAP表达增加。     

加巴喷丁复合吗啡预防慢性压迫坐骨神经致痛觉敏化的疗效分析

目的观察加巴喷丁复合吗啡预防性镇痛对大鼠慢性压迫坐骨神经（CCI）后导致的机械缩足阈变化以及脊髓背角肿瘤坏死因子-α（TNF-α）表达的影响。方法随机选择重量（180±20）g的成年雄性SD大鼠24只,分为假手术组（S组）、模型组（M组）、预防性镇痛组（P组）和常规镇痛组（N组）。观察不同方式给药的模型组和对照组大鼠的行为学变化。术后10d分离脊髓通过免疫组化检测TNF-α水平的变化。结果术前各组大鼠机械痛阈差异无统计学意义,与M组相比,手术后各时段S、P、N组都存在不同程度的改变,差异均有统计学意义（P〈0.05）;P、N组TNF-α的积分光密度均值（IOD）水平分别为（0.2185±0.01980）、（0.2301±0.01386）,与M组的（0.2902±0.01325）比较明显降低,差异均有统计学意义（P〈0.05）。结论加巴喷丁复合吗啡对大鼠采用预防性镇痛有较好的效果,可显著降低CCI后导致的机械痛阈,降低TNF-α在脊髓背角的表达。     

脊髓刺激术对神经病理性痛模型大鼠脊髓背角内NR2B受体和星形胶质细胞激活的影响

目的:探讨脊髓刺激术(spinal cord stimulation,SCS)对L5脊神经结扎(spinal nerve ligation,SNL)诱导的神经病理性痛(neuropathic pain,NP)大鼠脊髓背角内NMDA受体亚单位NR2B的表达和星形胶质细胞激活的影响。方法:成年雄性SD大鼠48只,随机分为4组:正常组(不做任何处理);SCS组(植入SCS装置并给予SCS刺激);SNL+sham SCS组(给予SNL手术并植入SCS装置,但不进行刺激);SNL+SCS组(SNL手术并给予SCS刺激)。SCS刺激是在SNL术后第6～10 d进行(8 h/d),第10 d刺激结束后处死动物。运用行为学方法检测慢性痛状态下大鼠后肢对机械性刺激的反应阈值;采用免疫组织化学染色和Western blot方法分别检测脊髓背角内NR2B和星形胶质细胞的标志物GFAP的表达变化。结果:(1)SNL术后大鼠手术侧后足机械性痛敏显著增加,第6～10 d给予SCS刺激后,可观察到大鼠的痛行为学表现有明显缓解;(2)免疫组化结果显示:与SNL+sham SCS组相比,SNL+SCS组大鼠脊髓背角内NR2B和GFAP免疫阳性细胞的数量显著减少;(3)Western blot结果显示:给予SCS刺激后,SNL大鼠腰膨大段脊髓背角内NR2B的表达量显著下调,同时GFAP的表达量也明显有所降低。结论:给予SCS刺激可以有效地缓解SNL模型大鼠的神经病理性痛的行为学表现;该作用可能与SCS刺激抑制脊髓背角内NR2B的表达和星形胶质细胞的激活密切相关。     

A partial L5 spinal nerve ligation induces a limited prolongation of mechanical allodynia in rats: An efficient model for studying mechanisms of neuropathic pain

The relationship between pain severity and the extent of injury to a peripheral nerve remains elusive. In this study, we compared the pain behavior resulting from partial (1/3–1/2 thickness) and full L5 spinal nerve ligation (SNL) in rats. The decrease in paw withdrawal threshold (PWT) to mechanical stimuli in the hindpaw ipsilateral to the injury was comparable in the two groups on days 3–21 post-injury. However, the decreased PWT recovered earlier in the partial SNL group than in the full SNL group. These observations suggest that the duration of neuropathic pain behavior, but not the early development of mechanical allodynia, is dependent on the extent of nerve injury. On days 6 and 15 post-injury, when the mechanical allodynia was similar in the two groups, systemic morphine induced a greater reduction of mechanical allodynia in the partial SNL group than in the full SNL group. Furthermore, in partial SNL rats, at post-injury time points when they had largely recovered from the neuropathic pain state, systemic administration of naloxone hydrochloride (day 53) or naloxone methiodide (a non-selective peripherally acting opioid receptor antagonist; day 64) or intra-plantar injection of naloxone methiodide rekindled mechanical pain hypersensitivity in the ipsilateral hindpaw, suggesting a prolonged activation of endogenous opioidergic pain-inhibition. Therefore, partial SNL in rats may represent an efficient model for studying the mechanisms of neuropathic pain, testing effects of analgesic/antihyperalgesic drugs, and understanding endogenous pain-inhibitory mechanisms that lead to reversal of the pain behavior with time.     

加巴喷丁对脊神经结扎大鼠背根神经节交感神经芽生的影响

目的:观察加巴喷丁干预后疼痛大鼠痛阈变化及背根神经节(DRGs)中交感神经芽生的改变。方法:将SD雄性大鼠随机分为正常对照组、模型组和加巴喷丁组,于术前及术后5 d每天检测大鼠痛阈变化;术后5 d取各组大鼠手术侧腰5和腰4及对侧腰5 DRG,观察DRGs中交感纤维数量及篮状结构的变化。结果:加巴喷丁可以显著抑制脊神经结扎引起的痛觉过敏;模型组(手术侧腰5及腰4)表现为交感神经节后纤维的异常增生,加巴喷丁干预后,手术侧腰5和腰4 DRGs TH-IR纤维及篮状结构的数量明显低于模型组。结论:加巴喷丁能提高疼痛大鼠痛阈,其机制可能是通过降低脊髓DRG中交感神经的芽生而产生镇痛作用。     

脊髓刺激术对神经病理性痛模型大鼠痛行为和脊髓背角内小胶质细胞激活的影响

目的:探讨脊髓刺激术(spinal cord stimulation,SCS)对神经病理性痛(neuropathic pain,NP)模型大鼠痛行为及脊髓背角内小胶质细胞激活的影响。方法:成年大鼠20只,随机分为4组:(1)正常对照组(control组);(2)SCS组:正常大鼠给予SCS刺激;(3)脊神经结扎(spinal nerve ligation,SNL)假刺激组(SNL+shamSCS组):SNL且植入SCS装置,但不刺激;(4)SNL+SCS组:SNL且给予SCS刺激。术前连续3 d、术后第5 d检测各组大鼠足底机械痛敏阈值(mechanical withdrawal threshold,MWT)。SCS组和SNL+SCS组术后第2-5 d给予SCS刺激,每d持续8 h;且在每次给予SCS 8 h刺激前进行90 min行为学测试,即SCS刺激30 min,以及刺激结束后的60 min内(共90 min),每15 min测量一次MWT。在第5 d给予SCS 8 h刺激结束后处死动物,利用免疫组织化学染色结合平均光密度(average optical density,AOD)分析的方法检测各组大鼠腰5节段脊髓背角内小胶质细胞特异性标志物OX-42的表达情况。结果:(1)行为学结果显示:术后第5 d,SNL+shamSCS组和SNL+SCS组大鼠手术侧后爪的MWT由术前26.00±0.0 g分别降至5.50±0.96 g和6.40±0.40 g(P<0.05);SNL+SCS组给予SCS刺激30 min后大鼠手术侧后爪的MWT明显有所提高,达16.20±2.60 g,与刺激前(6.40±0.40 g)相比有显著性差异(P<0.05);但停止SCS刺激60 min后,大鼠的MWT明显有所下降,与刺激前几乎没有明显差别。(2)免疫组化染色结果显示:术后第5 d,SNL+SCS组脊髓背角内OX-42的表达明显弱于SNL+shamSCS组,但二者都强于control组和SCS组;AOD结果也证实:SNL+SCS组大鼠脊髓背角内OX-42的AOD(1.29±0.28)明显低于SNL+shamSCS组(2.66±0.38),但仍高于control组(0.14±0.21)和SCS组(0.24±0.08)。结论:SCS对SNL模型大鼠的神经病理性痛有较好的镇痛效果;该作用可能与SCS刺激显著抑制脊髓背角内小胶质细胞的激活密切相关。     

Bipolar spinal cord stimulation attenuates mechanical hypersensitivity at an intensity that activates a small portion of A-fiber afferents in spinal nerve-injured rats

Spinal cord stimulation (SCS) is used clinically to treat neuropathic pain states, but the precise mechanism by which it attenuates neuropathic pain remains to be established. The profile of afferent fiber activation during SCS and how it may correlate with the efficacy of SCS-induced analgesia are unclear. After subjecting rats to an L5 spinal nerve ligation (SNL), we implanted a miniature quadripolar electrode similar to that used clinically. Our goal was to determine the population and number of afferent fibers retrogradely activated by SCS in SNL rats by recording the antidromic compound action potential (AP) at the sciatic nerve after examining the ability of bipolar epidural SCS to alleviate mechanical hypersensitivity in this model. Notably, we compared the profiles of afferent fiber activation to SCS between SNL rats that exhibited good SCS-induced analgesia (responders) and those that did not (nonresponders). Additionally, we examined how different contact configurations affect the motor threshold (MoT) and compound AP threshold. Results showed that three consecutive days of SCS treatment (50 Hz, 0.2 ms, 30 min, 80–90% of MoT), but not sham stimulation, gradually alleviated mechanical hypersensitivity in SNL rats. The MoT obtained in the animal behavioral study was significantly less than the Aα/β-threshold of the compound AP determined during electrophysiological recording, suggesting that SCS could attenuate mechanical hypersensitivity with a stimulus intensity that recruits only a small fraction of the A-fiber population in SNL rats. Although both the MoT and compound AP threshold were similar between responders and nonresponders, the size of the compound AP waveform at higher stimulation intensities was larger in the responders, indicating a more efficient activation of the dorsal column structure in responders.     

全脑照射后对小鼠血脑屏障通透性和室管膜下区细胞增殖的影响

目的:探讨60Co-γ射线(Gy)全脑照射后对小鼠血脑屏障通透性和室管膜下区神经干细胞增殖的影响。方法:112只健康小鼠随机分成0 Gy组(对照组),5 Gy照射组(小剂量照射组),15 Gy照射组(中等剂量照射组)和30 Gy照射组(大剂量照射组),每组28只。各组随机取出7只分别于照射后1周和4周测定各组小鼠脑组织伊文思蓝的含量,7只观察室管膜下区的BrdU+细胞形态和数量。结果:(1)照射后1周,15 Gy组和30Gy组脑组织伊文思蓝含量明显升高(P<0.05),室管膜下区的BrdU+细胞数明显降低(P<0.05);(2)照射后4周,15 Gy剂量照射组脑组织伊文思蓝含量和室管膜下区的BrdU+细胞数均恢复到对照组水平(P>0.05),而30Gy剂量照射组脑组织伊文思蓝含量仍明显升高(P<0.05),BrdU+细胞数也未见恢复(P<0.05)。结论:全脑照射后血脑屏障破坏可能对室管膜下区的细胞增殖有进一步抑制作用。     

Spatial and non-spatial performance in mutant mice devoid of otoliths

In the preclinical study of pain, two commonly used pain models are the L5 spinal nerve ligation (SNL) and the injection of carrageenan. Using a modified place escape/avoidance paradigm (mPEAP), a novel behavioral test that quantifies aversive behavior evoked by painful stimuli, we directly compared the affective component of the SNL and inflammation models. Fifty three Sprague-Dawley rats underwent baseline mechanical paw withdrawal threshold (MPWT) and mPEAP testing followed by an L5 SNL or sham surgery for the left paw and then a carrageenan or saline injection for the right paw. After recovering, animals underwent post-manipulation MPWT and mPEAP tests. Both pain conditions produced mechanical hypersensitivity, and animals with a single-paw condition demonstrated escape/avoidance behavior in response to stimulation of the affected paw. Animals with the bilateral pain condition did not show a preference for stimulation of one paw versus the other paw, and the avoidance behavior was not significantly different from the sham/saline control. The results indicate that the pain models are associated with significant avoidance behavior and that they produce comparable degrees of pain affect. These findings advance the preclinical study of pain by validating the simultaneous utilization of the SNL and inflammation models and will allow future studies that combine pain conditions to more closely resemble clinical conditions.     

Low barometric pressure aggravates neuropathic pain in guinea pigs

Several clinical studies have demonstrated a consistent relationship between changes in meteorological factors, particularly barometric pressure, and pain intensity in subjects with chronic pain. We have previously demonstrated that exposure to artificially low barometric pressure (LP) intensifies pain-related behaviors in rats with neuropathic pain. In the present study, guinea pigs with unilateral L5 spinal nerve ligation (SNL) were placed in a pressure-controlled chamber and subjected to LP of 10 or 27 hPa below the ambient pressure. The SNL surgery led to increased hindpaw withdrawal frequencies to 34-, 59-, and 239-mN von Frey filaments (VFFs). When the SNL animals were subjected to both LP exposures consecutively, the hindpaw withdrawal frequencies further increased; the effect was most significant when the animals were exposed to LP 27 hPa below ambient pressure. In contrast, no change was seen in a group of sham-operated control animals. These results indicate that fluctuations in LP within the range of natural weather patterns can potentiate neuropathic pain in guinea pigs.     

Anatomical localization and expression pattern for the NMDA-2D receptor subunit in a rat model of neuropathic pain

The N-methyl-d-aspartate receptor (NMDAR) has been implicated in the etiology of chronic pain. In this regard, this study sought to characterize the localization and expression pattern for the NMDAR-2D subunit in a rat model of neuropathic pain. To this end, one group of rats, 3 weeks post-dorsal root rhizotomy (DRR) and a second group, 3 weeks post-spinal nerve ligation (SNL) and sham surgery, were generated. Dorsal root ganglia (DRG) and/or lumbar spinal cord were excised from DRR, naïve, SNL and sham rats. Both immunohistochemical and real-time PCR analysis confirmed discrete NMDAR-2D subunit expression within the DRG and dorsal horn. However, no overt differences in staining intensity or expression were noted between DRG and spinal cord sections obtained from the different surgical groups. Results also demonstrated that the NMDAR-2D subunit was present within Neu N+ cells in the spinal cord and DRG, but excluded from cells labeled with the astrocytic marker, GFAP, and the microglial maker, OX-42. Lastly, the NMDAR-2D subunit was not co-expressed within neurokinin-1 (NK-1)+ or neurofilament-52 (N-52)+ neurons, but the antibody did co-label a number of isolectin B4+ (IB4) DRG cells. Together, these findings seem to suggest that the NMDAR-2D receptor subunit is present within the cell body region of a population of small diameter sensory afferents and post-synaptically within second order dorsal horn neurons. Although these data suggest that the NMDAR-2D subunit is well poised anatomically to modulate pain neurotransmission, the expression pattern for this subunit is not altered in rats demonstrating the presence of neuropathic-like pain behavior.