低频电针对脊神经结扎大鼠痛敏化的干预作用

目的观察低频电针对脊神经结扎神经病理痛大鼠模型痛敏化的干预作用,探讨其可能的外周痛敏化调节机制。方法建立大鼠L5脊神经结扎模型,电针足三里和昆仑穴,观察大鼠痛觉超敏反应,运用Western blotting 法检测L4、L5背根神经节(DRG)辣椒素受体(TRPV1)与P 物质(SP)水平,采用TRPV1 激动剂6'-IRTX进行验证。结果脊神经结扎大鼠出现明显的痛敏化反应,术侧L4 DRG TRPV1 和L5 DRG SP 水平升高(P<0.05);低频电针能减轻模型大鼠的痛敏反应,抑制TRPV1、SP 水平上升(P<0.05)。6'-IRTX腹腔注射能拮抗低频电针的抗痛敏化作用。结论低频电针可减轻痛敏化,发挥对神经病理痛的治疗作用,其机制可能与其有效调控DRG TRPV1 和SP有关。     

鞘内注射PKC抑制剂对神经病理痛大鼠脊髓背角NMDAR、CGRP表达的影响

目的：观察鞘内注射PKC抑制剂对神经病理痛大鼠脊髓背角N-甲基-D-天冬氨受体（NMDAR）、降钙素基因相关肽（CGRP）表达的影响。方法：健康雄性SD大鼠36只,体重220～280g。随机分为4组（n=9）：对照组（C组）、假手术组（Sham组）、坐骨神经分支选择结扎切断模型组（SNI组）和PKC抑制剂组（P组）。SNI组和P组制备SNI模型,P组在SNI术后14d内每天鞘内注射PKC抑制剂11μg,其余各组给予等容量生理盐水。在SNI术前1d（基础值）及术后14d每次注射药物后测定机械痛阈和热缩足潜伏期,分别于SNI术后2、7、14d注射药物后各处死大鼠3只,采用免疫组化法测定L5节段脊髓背角NMDAR和CGRP表达水平。结果：与C组和Sham组比较,SNI组机械痛阈降低,NMDAR和CGRP表达上调（P〈0.01）,热缩足潜伏期差异无统计学意义（P〉0.05）。与SNI组比较,P组机械痛阈升提高,热缩足潜伏期延长,NMDAR和CGRP表达下调（P〈0.01）。结论：鞘内注射PKC抑制剂对神经病理痛大鼠具有明显的抗伤害效应,并抑制大鼠脊髓背角NMDAR和CGRP表达。     

低频电针对脊髓损伤致急性自发痛模型大鼠急性痛超敏的影响

目的：观察低频电针对脊髓损伤致急性自发痛模型大鼠急性痛超敏和自发痛行为学的影响。方法： 60只SD大鼠随机均分为对照组,模型组及低、中、高频电针组,每组12只。模型组和低、中、高频电针组建 立急性脊髓 L2节段损伤模型。低、中、高频电针组分别用低频（2 Hz）、中频（50 Hz）、高频（100 Hz）电刺激 T8～T12节段夹脊穴和双侧“昆仑”和“足三里”,25 min/次,1 次/d,共14 d。治疗结束后,观察各组大鼠自发疼 痛行为,用足底热辐射测痛仪检测各组大鼠热缩足潜伏期（PWL）和50%机械性缩足阈值（PWT）;记录L1段 体感诱发电位（SEP）潜伏期及N波、P波的波幅。结果：与对照组相比,模型组的自发疼痛行为学动作的发 生次数增多（P＜0.05）;痛阈值降低（均P＜0.05）,急性痛超敏发生率增高（P＜0.05）,PWL和PWT降低（均 P＜0.05）,SEP潜伏期及N波、P波波幅均增加（均P＜0.05）。与模型组相比,3个电针组的自发疼痛行为学 动作的发生次数降低（均 P＜0.05）,痛阈值升高（均 P＜0.05）,急性痛超敏发生率降低（P＜0.05）,PWL 和 PWT降低（均P＜0.05）,SEP潜伏期及N波、P波波幅降低均P＜0.05）,且低频电针组的疗效优于中、高频电 针组（均P＜0.05）。结论：低频电针可提高脊髓损伤大鼠的痛阈,减轻急性自发痛超敏,改善自发痛引起的 行为学变化。     

鞘内注射PKC抑制剂对神经病理痛大鼠脊髓背角NMDAR、CGRP表达的影响木

目的:观察鞘内注射PKC抑制剂对神经病理痛大鼠脊髓背角N-甲基-D-天冬氨受体(NMDAR)、降钙素基因相关肽(CGRP)表达的影响.方法:健康雄性SD大鼠36只,体重220～280g.随机分为4组(n=9):对照组(C组)、假手术组(Sham组)、坐骨神经分支选择结扎切断模型组(SNI组)和PKC抑制剂组(P组).SNI组和P组制备SNI模型,P组在SNI术后14d内每天鞘内注射PKC抑制剂11μg,其余各组给予等容量生理盐水.在SNI术前ld(基础值)及术后14d每次注射药物后测定机械痛阈和热缩足潜伏期,分别于SNI术后2、7、14d注射药物后各处死大鼠3只,采用免疫组化法测定L5节段脊髓背角NMDAR和CGRP表达水平.结果:与C组和Sham组比较,SNI组机械痛阈降低,NMDAR和CGRP表达上调(P<0.01),热缩足潜伏期差异无统计学意义(P>0.05).与SNI组比较,P组机械痛阈升提高,热缩足潜伏期延长,NMDAR和CGRP表达下调(P<0.01).结论:鞘内注射PKC抑制剂对神经病理痛大鼠具有明显的抗伤害效应,并抑制大鼠脊髓背角NMDAR和CGRP表达.     

电针对股骨骨折大鼠骨痂内神经肽表达水平的影响

目的研究电针刺激穴位对股骨骨折大鼠骨痂内神经肽表达水平的影响。 方法将40只雄性Wistar大鼠随机分为骨折组和电针组,2组大鼠均制成股骨骨折模型,其中电针组大鼠于骨折模型建立后给予电针刺激。2组大鼠分别于术后第4,7,14及28天时各取5只处死,并采集骨折部位组织制成切片。采用免疫组织化学染色法检查各组大鼠术后不同时间点骨痂内降钙素基因相关肽（CGRP）及P物质（SP）表达情况。 结果电针组大鼠在术后骨折愈合不同阶段,其骨痂内各种细胞胞浆中均有CGRP、SP阳性颗粒表达,且出现时间较骨折组早,维持时间较骨折组长;图像分析系统显示电针组骨痂内CGRP、SP光密度值明显高于骨折组,组间差异具有统计学意义（P<0.05）。 结论电针刺激穴位能显著提高骨折大鼠骨痂内CGRP、SP等神经肽表达,推测电针可通过影响神经肽水平参与并调节骨折愈合过程。     

电针刺激对脑缺血再灌注大鼠神经功能恢复的影响

目的 观察电针刺激对脑缺血再灌注大鼠缺血侧脑梗死体积、脑细胞凋亡及大脑皮质蛋白激酶A（PKA）表达的影响,初步探讨电针刺激的脑保护作用机制。 方法 采用随机数字表法将120只健康成年雄性SD大鼠分为假手术组、模型组、电针组及电针预刺激组。采用线栓法将模型组、电针组及电针预刺激组大鼠制成左侧大脑中动脉阻塞（MCAO）2 h再灌注模型。电针预刺激组大鼠于造模前采用电针连续刺激百会、大椎及右侧内关穴5 d,每日1次,每次30 min。电针组和电针预刺激组均于制模后继续电针刺激百会、大椎及右侧内关穴,每日1次,每次30 min。模型组及假手术组大鼠在相同时间内予以捆绑固定,不给予任何特殊处理。于电针刺激5 d、10 d时,分别采用Garcia评分法评价各组大鼠神经功能缺损情况,采用氯化三苯基四氮唑(TTC)染色法观察各组大鼠缺血侧脑梗死体积,通过流式细胞仪测定各组大鼠缺血侧皮质细胞凋亡率,采用免疫组织化学法测定各组大鼠缺血侧皮质PKA阳性细胞表达率。 结果 模型组大鼠神经功能严重受损,假手术组大鼠无神经功能缺陷。电针组、电针预刺激组在制模后5 d、10 d时其Garcia评分、脑梗死体积、脑细胞凋亡率及PKA阳性细胞表达率均明显优于模型组同时相点水平（P<0.05）;并且电针预刺激组上述时间点Garcia评分、脑梗死体积、脑细胞凋亡率及PKA阳性细胞表达率亦显著优于电针组同时相点水平（P<0.05）。 结论 电针刺激能促进脑缺血再灌注大鼠受损神经功能恢复,如辅以电针预刺激能进一步改善受损神经功能,其疗效明显优于单纯电针刺激;关于电针预刺激的脑保护作用机制可能与减小脑梗死体积、抑制脑细胞凋亡、促进PKA阳性细胞表达等因素有关。     

基于NGF/TrKA/TRPV1通路探讨电针改善功能性消化不良大鼠胃高敏感性

目的 探讨电针对功能性消化不良（FD）大鼠胃高敏感性的作用效果及机制。方法 将30只大鼠随机平均分为空白组、模型组、电针组、抑制剂组、电针+抑制剂组。空白组不予以特殊处理，其余各组采用多因素刺激法进行造模。造模完成后，模型组常规饲养，电针组和电针+抑制剂组予以每天电针足三里，抑制剂和电针+抑制剂组予以每天腹腔注射神经生长因子（NGF）抑制剂。采用胃内球囊置入检测胃高敏感性和胃顺应性，采用甲胺蓝染色观察胃肥大细胞活化程度，采用免疫组化法检测胃瞬时受体电位香草酸亚型1(TRPV1)定位表达，采用免疫印迹检测胃NGF/原肌球蛋白受体激酶（TrkA）/TRPV1蛋白表达，采用酶联免疫吸附检测胃降钙素基因相关肽（CGRP）含量。结果 相比于空白组，模型组大鼠体重增长缓慢，胃敏感性增高、顺应性降低，胃肥大细胞数和脱颗粒率显著增加，NGF、TrKA、TRPV1的蛋白表达和CGRP含量显著升高；与模型组比较，电针组、抑制剂组和电针+抑制剂组大鼠体重增加，胃高敏感性和顺应性显著改善，肥大细胞数目和活化程度显著降低，胃NGF/TrKA/TRPV1蛋白表达和CGRP含量显著降低；且相比于电针组和抑制剂组，电...     

鞘内单次注射吗啡对神经病理痛大鼠脊髓背角CGRP表达的影响

目的:观察鞘内单次注射吗啡对神经病理痛大鼠脊髓背角降钙素基因相关肽(Calcitonin gene-related peptide CGRP)表达的影响.方法:20只健康雄性SD大鼠,体重200～270 g,随机分为4组:对照组(C组,n=5),假手术组(S组,n=5),生理盐水组(N组,n=5),吗啡组(M组,n=5).C组不做任何处理,其它3组均根据改良Yaksh法进行鞘内置管;N组和M组制备神经病理痛模型(SNI模型),制模2 d后,N组和M组分别鞘内注射生理盐水和吗啡10μg,容量为20μl.每组均在SNI术前1d(基础值)到术后2d内每天测定机械痛阈和热缩足潜伏期,并全部在注药后2h处死大鼠,用免疫组织化学方法观察大鼠L5节段水平脊髓背角CGRP的表达.结果:与C组和S组比较,N组机械痛阈降低,CGRP表达上调(P<0.05),热缩足潜伏期差异无统计学意义(P0.05).与N组比较,M组机械痛阈升高,热缩足潜伏期延长,CGRP表达下调(P<0.05).结论:鞘内单次注射吗啡对神经病理痛大鼠在产生镇痛效应时引起脊髓背角CGRP表达下调.     

电针对慢性脑低灌注大鼠认知功能及海马JAK2、STAT3 mRNA表达的影响

目的 探讨电针对慢性脑低灌注（CCH）大鼠认知功能及海马JAK2、STAT3 mRNA表达水平的影响。 方法 选取清洁级健康雄性SD大鼠40只,分为假手术组10只、手术组30只,手术组采用双侧颈总动脉结扎法制作CCH模型,再随机分为模型组、电针1周组、电针4周组3个亚组,各亚组均为10只。电针4周组采用2/100 Hz疏密波电针连续干预4周,电针1周组仅在评定前最后1周采用电针干预。采用Morris水迷宫系统评定各组大鼠的认知功能,采用逆转录-聚合酶链式反应（RT-PCR）检测JAK2 mRNA、STAT3 mRNA的表达水平。 结果 与假手术组比较,手术组BCCAO术后局灶性脑血流水平显著下降,且低于组内手术前（P<0.05）。与模型组比较,电针4周组第3天开始,逃避潜伏期改善,差异有统计学意义（P<0.05）,电针1周组第5天逃避潜伏期显著改善,差异有统计学意义（P<0.05）,电针4周组目标象限停留时间明显延长,差异有统计学意义（P<0.05）,电针1周组、电针4周组JAK2/STAT3 mRNA表达水平均下降,电针4周组明显下降,差异有统计学意义（P<0.05）。与电针1周组比较,电针4周组第5天逃避潜伏期改善（P<0.05）,目标象限停留时间延长（P<0.05）,JAK2 mRNA下降更明显（P<0.05）。 结论 电针能改善CCH大鼠的认知功能,早期干预作用更显著,其机制可能是通过抑制脑低灌注后JAK2/STAT3通路的过度活化,进而减轻脑损伤。     

鞘内注射μ、δ阿片受体激动剂对大鼠骨癌痛的影响

目的: 比较鞘内及RVM区注射MOR和DOR激动剂对大鼠骨癌痛及神经病理痛的痛行为学的影响，探讨MOR和DOR在骨癌痛发病机制中的作用。方法：雌性Wistar大鼠，随机分为14组：BCP+NS组、BCP+DAMGO（1、5、10μg）组、BCP+DPDPE（0.1、0.5、1μg）组、SNI+NS组、SNI+DAMGO（0.5、1、5μg）组、SNI+ DPDPE（0.1、0.5、1μg）组。注药20min后，观察不同剂量药物对大鼠触诱发痛及机械痛觉过敏反应的影响。结果：在骨癌痛大鼠，鞘内注射DAMGO 1μg 仅轻微升高大鼠双侧后爪对von fray的缩爪阈值；DAMGO 5、10μg可显著升高大鼠双侧后爪对von fray的缩爪阈值，明显缩短术侧后爪对针刺的缩爪持续时间（P＜0.05）；DPDPE（0.1、0.5、1μg）对骨癌痛大鼠双侧后爪的触诱发痛和术侧后爪的机械痛觉过敏反应呈剂量依赖性的抑制作用；在SNI模型大鼠，DAMGO和DPDPE均呈剂量依赖性的抑制大鼠的触诱发痛和机械痛觉过敏反应（P＜0.05）。结论: 鞘内给予μ、δ阿片受体选择性激动剂对大鼠骨癌痛及神经病理性疼痛均有明显的镇痛作用，所需的剂量在骨癌痛大于神经病理性疼痛。     

Intrathecal AAV Serotype 9-mediated Delivery of shRNA Against TRPV1 Attenuates Thermal Hyperalgesia in a Mouse Model of Peripheral Nerve Injury

Gene therapy for neuropathic pain requires efficient gene delivery to both central and peripheral nervous systems. We previously showed that an adenoassociated virus serotype 9 (AAV9) vector expressing short-hairpin RNA (shRNA) could suppress target molecule expression in the dorsal root ganglia (DRG) and spinal cord upon intrathecal injection. To evaluate the therapeutic potential of this approach, we constructed an AAV9 vector encoding shRNA against vanilloid receptor 1 (TRPV1), which is an important target gene for acute pain, but its role in chronic neuropathic pain remains unclear. We intrathecally injected it into the subarachnoid space at the upper lumbar spine of mice 3 weeks after spared nerve injury (SNI). Delivered shTRPV1 effectively suppressed mRNA and protein expression of TRPV1 in the DRG and spinal cord, and it attenuated nerve injury-induced thermal allodynia 10–28 days after treatment. Our study provides important evidence for the contribution of TRPV1 to thermal hypersensitivity in neuropathic pain and thus establishes intrathecal AAV9-mediated gene delivery as an investigative and potentially therapeutic platform for the nervous system.     

Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats

Peripheral nerve injuries that provoke neuropathic pain are associated with microglial activation in the spinal cord. We have investigated the characteristics of spinal microglial activation in three distinct models of peripheral neuropathic pain in the rat: spared nerve injury (SNI), chronic constriction injury, and spinal nerve ligation. In all models, dense clusters of cells immunoreactive for the microglial marker CD11b formed in the ipsilateral dorsal horn 7 days after injury. Microglial expression of ionised calcium binding adapter molecule 1 (Iba1) increased by up to 40% and phosphorylation of p38 mitogen-activated protein kinase, a marker of microglial activity, by 45%. Expression of the lysosomal ED1-antigen indicated phagocytic activity of the cells. Unlike the peripheral nerve lesions, rhizotomy produced only a weak microglial reaction within the spinal gray matter but a strong activation of microglia and phagocytes in the dorsal funiculus at lumbar and thoracic spinal cord levels. This suggests that although degeneration of central terminals is sufficient to elicit microglial activation, it does not account for the inflammatory response in the dorsal horn after peripheral nerve injury. Early intrathecal treatment with low-dose methotrexate, beginning at the time of injury, decreased microglial activation, reduced p38 phosphorylation, and attenuated pain-like behavior after SNI. In contrast, systemic or intrathecal delivery of the glucocorticoid dexamethasone did not inhibit the activation of microglia or reduce pain-like behavior. We confirm that microglial activation is crucial for the development of pain after nerve injury, and demonstrates that suppression of this cellular immune response is a promising approach for preventing neuropathic pain.     

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain

Using the chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord, and identified SIP30 as a gene whose expression was elevated after CCI. SIP30 was previously shown to interact with SNAP25, but whose function was otherwise unknown. We now show that in the spinal cord, SIP30 was present in the dorsal horn laminae where the peripheral nociceptive inputs first synapse, co-localizing with nociception-related neuropeptides CGRP and substance P. With the onset of neuropathic pain after CCI surgery, SIP30 mRNA and protein levels increased in the ipsilateral side of the spinal cord, suggesting a potential association between SIP30 and neuropathic pain. When CCI-upregulated SIP30 was inhibited by intrathecal antisense oligonucleotide administration, neuropathic pain was attenuated. This neuropathic pain-reducing effect was observed both during neuropathic pain onset following CCI, and after neuropathic pain was fully established, implicating SIP30 involvement in the development and maintenance phases of neuropathic pain. Using a secretion assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of synaptic vesicles available for exocytosis, pointing to a potential function for SIP30. These results suggest a role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.     

损伤大鼠L5脊神经及其前后根对痛行为的影响

目的:观察大鼠腰5脊神经和脊神经根不同部位损伤对诱导神经病理性疼痛的不同作用。方法:采用腰5脊神经结扎加切断(lumbar5 spinal nerve ligation,L5 SNL)、腰5前根切除(lumbar5 ventral rhizotomy,L5 VR)和腰5背根切除(lumbar5 dorsal rhizotomy,L5 DR)诱导大鼠痛觉过敏,结合痛行为学测试观察病理性疼痛的发展过程。结果:(1)L5SNL可引起大鼠病理性疼痛。双侧后肢50%撤足阈值(paw withdrawal threshold,PWT)和撤足潜伏期(paw withdrawal latency,PWL)于术后1d明显下降,痛觉过敏的症状,在同侧后肢持续了5周,在对侧后肢也保持3周。(2)L5 VR也可诱导大鼠产生病理性疼痛。双侧后肢50%PWT和PWL于术后1d明显降低,并维持到了术后第5周。(3)L5DR没有引起大鼠产生痛觉过敏症状。与术前基础值和假手术组比较,L5DR后50%PWT和PWL均无明显变化。结论:选择性损伤运动纤维和损伤脊神经均能诱导大鼠产生病理性疼痛,但脊神经背根损伤不引起痛觉过敏。     

A-995662 [(R)-8-(4-methyl-5-(4-(trifluoromethyl)phenyl)oxazol-2-ylamino)-1,2,3,4-tetrahydronaphthalen-2-ol], a novel,selective TRPV1 receptor antagonist,reduces spinal release of glutamate and CGRP in a rat knee joint pain model

The TRPV1 antagonist A-995662 demonstrates analgesic efficacy in monoiodoacetate-induced osteoarthritic (OA) pain in rat, and repeated dosing results in increased in vivo potency and a prolonged duration of action. To identify possible mechanism(s) underlying these observations, release of neuropeptides and the neurotransmitter glutamate from isolated spinal cord was measured. In OA rats, basal release of glutamate, bradykinin and calcitonin gene-related peptide (CGRP) was significantly elevated compared to naïve levels, whereas substance P (SP) levels were not changed. In vitro studies showed that capsaicin-evoked TRPV1-dependent CGRP release was 54.7 ± 7.7% higher in OA, relative to levels measured for naïve rats, suggesting that TRPV1 activity was higher under OA conditions. The efficacy of A-995662 in OA corresponded with its ability to inhibit glutamate and CGRP release from the spinal cord. A single, fully efficacious dose of A-995662, 100 μmol/kg, reduced spinal glutamate and CGRP release, while a single sub-efficacious dose of A-995662 (25 μmol/kg) was ineffective. Multiple dosing with A-995662 increased the potency and duration of efficacy in OA rats. Changes in efficacy did not correlate with plasma concentrations of A-995662, but were accompanied with reductions in spinal glutamate release. These findings suggest that repeated dosing of TRPV1 antagonists enhances therapeutic potency and duration of action against OA pain, at least in part, by the sustained reduction in release of glutamate and CGRP from the spinal cord.     

Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats.

We developed a rat model of oral cancer pain by inoculating cancer cells into the lower gingiva. A squamous cell carcinoma (SCC) derived from Fisher rats, SCC-158, was inoculated into the subperiosteal tissue on the lateral side of the lower gingiva in male Fisher rats. Inoculation of cancer cells induced marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve area. Infiltration of the tumor cells into the mandible and the completely encompassed inferior alveolar nerve was observed. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, ATP receptor (P2X(3))-, and capsaicin receptor (TRPV1)-immunoreactive cells strikingly increased in the small-cell group of trigeminal ganglia (TGs) after tumor cell inoculation. The TRPV1-immunoreactive cells also increased in the medium- and large-cell groups. Retrograde tracing combined with immunofluorescence techniques revealed the increased expression of peptides and the receptors in maxillary nerve afferent neurons. These results suggest that inoculation of SCC cells into the lower gingiva produces mechanical allodynia and thermal hyperalgesia, indicating the establishment of a novel rat model of oral cancer pain. Increased expression of CGRP, SP, P2X(3), and TRPV1 in the TG may be involved in the behavioral changes in this model. PERSPECTIVE: To clarify the mechanisms of oral cancer pain, we examined the expression of calcitonin gene-related peptide, substance P, ATP receptor P2X(3), and capsaicin receptor TRPV1 in trigeminal ganglia. Characterizations of these molecular systems which mediate pain perception are important to develop novel clinical tools for promoting relief of oral cancer pain.     

Interdependent regulation of afferent renal nerve activity and renal function: role of transient receptor potential vanilloid type 1, neurokinin 1, and calcitonin gene-related peptide receptors

Our previous studies have shown that the activation of the transient receptor potential vanilloid type 1 (TRPV1) expressed in the renal pelvis leads to an increase in ipsilateral afferent renal nerve activity (ARNA) and contralateral renal excretory function, but the molecular mechanisms of TRPV1 action are largely unknown. This study tests the hypothesis that activation of receptors of neurokinin 1 (NK1) or calcitonin gene-related peptide (CGRP) by endogenously released substance P (SP) or CGRP following TRPV1 activation, respectively, governs TRPV1-induced increases in ARNA and renal excretory function. Capsaicin (CAP; 0.04, 0.4, and 4 nM), a selective TRPV1 agonist, administered into the renal pelvis dose-dependently increased ARNA. CAP (4 nM)-induced increases in ipsilateral ARNA or contralateral urine flow rate (Uflow) and urinary sodium excretion (UNa) were abolished by capsazepine (CAPZ), a selective TRPV1 antagonist, or 2-[1-imino-2-(2-methoxyphenyl)ethyl]-7,7-diphenyl-4-perhydroisoindolone (3aR,7aR) (RP67580) or cis-2-(diphenylmethyl)-N-[(2-iodophenyl)-methyl]-1 azabicyclo[2.2.2]octan-3-amine (L703,606), selective NK1 antagonists, but not by CGRP8-37, a selective CGRP receptor antagonist. Both SP (7.4 nM) and CGRP (0.13 muM) increased ARNA, Uflow, or UNa, and increases in these parameters induced by CGRP but not SP were abolished by CAPZ. CAP at 4 nM perfused into the renal pelvis caused the release of SP and CGRP, which was blocked by CAPZ but not by RP67580, L703,606, or CGRP8-37. Immunofluorescence results showed that NK1 receptors were expressed in sensory neurons in dorsal root ganglion and sensory nerve fibers innervating the renal pelvis. Taken together, our data indicate that NK1 activation induced by SP release upon TRPV1 activation governs TRPV1 function and that a TRPV1-dependent mechanism is operant in CGRP action.     

脊神经结扎神经病理痛模型大鼠脊髓星形胶质细胞激活与痛行为的关系

目的：研究L5脊神经结扎模型大鼠脊髓星形胶质细胞的激活与痛行为之间的关系。方法：44只雄性SD大鼠180—220g，随机分成4组，分别为假手术组、脊神经结扎1天、3天和7天组。行为学上使用von Frey Hair测定大鼠在上述各时间点50％缩足阈的变化（n=8），星形胶质细胞的激活使用免疫组织化学方法观察其特异性标志物GFAP的染色情况（n=3）。结果：（1）脊神经结扎后1天动物出现机械性痛超敏，3天和7天痛行为稳定并持续存在；假手术组未见显著变化。（2）结扎侧脊髓背角星形胶质细胞在术后1天发生激活，3天和7天可见星形胶质细胞强烈的激活反应，假手术组亦可见轻微的激活。（3）脊神经结扎后，星形胶质细胞发生了激活，其激活程度和痛行为的产生和维持紧密相关。结论：脊髓背角星形胶质细胞的激活可能在神经病理痛中发挥作用。