Substance P promotes epidural fibrosis via induction of type 2 macrophages

In response to spinal surgery,neurons secrete a large amount of substance P into the epidural area.Substance P is involved in macrophage differentiation and fibrotic disease.However,the specific roles and mechanisms of substance P in epidural fibrosis remain unclear.In this study,we established a mouse model of L1–L3 laminectomy and found that dorsal root ganglion neurons and the macrophages infiltrating into the wound area released sphingolipids.In vitro experiments revealed that type 1 macrophages secreted substance P,which promoted differentiation of type 1 macrophages towards a type 2 phenotype.High-throughput mRNA-seq analysis revealed that the sphingolipid metabolic pathway may be involved in the regulation of type 2 macrophages by substance P.Specifically,sphingomyelin synthase 2,a component of the sphingolipid metabolic pathway,promoted M2 differentiation in substance P-treated macrophages,while treating the macrophages with LY93,a sphingomyelin synthase 2 inhibitor,suppressed M2 differentiation.In addition,substance P promoted the formation of neutrophil extracellular traps,which further boosted M2 differentiation.Blocking substance P with the neurokinin receptor 1 inhibitor RP67580 decreased the number of M2 macrophages in the wound area after spinal surgery and alleviated epidural fibrosis,as evidenced by decreased fibronectin,α-smooth muscle actin,and collagen I in the scar tissue.These results demonstrated that substance P promotes M2 macrophage differentiation in epidural fibrosis via sphingomyelin synthase 2 and neutrophil extracellular traps.These findings provide a novel strategy for the treatment of epidural fibrosis.

Effect of electro-acupuncture on substance P, its receptor and corticotropin-releasing hormone in rats with irritable bowel syndrome

AIM： To investigate the effect and mechanism of electro-acupuncture lEA） at ST25 and ST37 on irritable bowel syndrome （IBS） of rats. METHODS： A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum （CR）. An abdominal withdrawal reflex （AWR） scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells （MC）, changes of substance P （SP） and substance P receptor （SPR） in colon and change of corticotropin-releasing hormone （CRH） in hypothalamus. RESULTS： The threshold of visceral sense was significantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION： EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.

Involvement of substance P and the NK-1 receptor in pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.

PKCε Mediates Substance P Inhibition of GABA_A Receptors-Mediated Current in Rat Dorsal Root Ganglion

The mechanism underlying the modulatory effect of substance P（SP） on GABA-activated response in rat dorsal root ganglion（DRG） neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA（1–1000 μmol/L） induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons（89.8 %） examined with whole-cell patch-clamp recordings. Bath application of GABA（1–1000 μmol/L） evoked a depolarizing response in 236 out of 257（91.8%） DRG neurons examined with intracellular recordings. Application of SP（0.001–1 μmol/L） suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1（NK1） receptors antagonist spantide but not by L659187 and SR142801（1 μmol/L, n=7）, selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C（PLC） inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca2＋-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the ＂pre-synaptic inhibition＂ evoked by GABA, which may explain its role in pain and neurogenic inflammation.

Substance P and its tachykinin NK1 receptor: a novel neuroprotective target for Parkinson's disease

Parkinson＇s disease （PD） is the most common motor neurode- generative disorder affecting approximately 4 million people worldwide. Although PD presents primarily with motor dysfunction, non-motor symptoms including cognitive decline, mood disorders, reduced olfaction and constipation are also of- ten present, with some of these non-motor symptoms even pre- senting prior to the onset of motor symptoms. It is well known that PD is largely caused by the gradual degeneration of dopa- minergic neurons within the substantia nigra pars compacta （SNc）, along with the presence of protein aggregates called Lewy bodies, which consist primarily of ct-synuclein and are found in the cytoplasm of surviving neurons. This ongoing cell loss and Lewy body pathology is not confined to the SNc, but is also seen in other brain regions implicated in PD pathogenesis such as the locus ceruleus.

Immunohistochemical study of substance P receptor (SPR) in early human placenta

We sought to determine whether substance P receptors (SPR) exist in human placenta and if do their cellular localization in placental villi, and to supply morphological evidence for the functional significance of SP in placental and fetal development. Methods: Immunohistochemical ABC method was used in the experiment. Results: Both syncytiotrophoblasts and cytotrophoblasts, stromal cells, capillary endothelium, lymphocytes in capillary cavity, and all blood islet in cells early human placenta showed SPR immunoreactivity in cytoplasm but with negative nuclei. Conclusion: SP produced by placental villi mediated by SPR might be responsible for the synthesis and release of placental hormone, the development of capillaries and the regulation of microcirculation in placental villi and fetal immune function.

Regulatory effect of nerve growth factor on release of substance P in cultured dorsal root ganglion neurons of rat

Objective To investigate the regulatory effects of nerve growth factor （NGF） on basal and capsaicin-induced release of neuropeptide substance P （SP） in primary cultured embryonic rat dorsal root ganglion （DRG） neurons. Methods DRGs were dissected from 15-day-old embryonic Wistar rats. DRG neurons were dissociated and cultured, and then exposed to different concentrations of NGF （10 ng/mL, 30 ng/mL, or 100 ng/mL） for 72 h. The neurons cultured in media without NGF served as control. RT-PCR were used for detecting the mRNAs of SP and vanilloid receptor 1 （VR1） in the DRG neurons. The SP basal and capsaicin （100 nmol/L）-induced release in the culture were measured by radioimmunoassay （RIA）. Results SP mRNA and VR1 mRNA expression increased in primary cultured DRG neurons in a dose-dependent manner of NGF. Both basal release and capsaicin-evoked release of SP increased in NGF-treated DRG neurons compared with in control group. The capsaicin-evoked release of SP also increased in a dose-dependent manner of NGF. Conclusion NGF may promote both basal release and capsaicin-evoked release of SP. NGF might increase the sensitivity of nociceptors by increasing the SP mRNA or VR1 mRNA.

^(125)I-substance P测定家兔脑内P物质受体的新方法

目的建立一种125I-substanceP（SP）测定脑内SP受体的方法。方法15只家兔断头后取下丘脑和腹侧延髓，低温（0－4℃）离心法制备突触小体，考马斯亮兰蛋白测定剂检测匀浆受体蛋白含量，不同浓度的125I-SP与受体制品孵育后，离心法终止配体受体结合反应，最后以γ闪烁计数仪测出总结合量和非特异结合量，计算特异结合值，根据Scatchard公式求出SP受体总数Bmax，和平衡解离常数Kd。结果1．下丘脑：Bmax107．8±5．2foml／mg受体蛋白，Kd=0.0149±0．004nM；延髓：Bmax33．90±2．22foml／mg受体蛋白；Kd＝0．0141±0．006nM。2．125I－SP终浓度为1．56×10-7M时特异结合与非特异结合比值高于终浓度为3．12×10-7M（P＜0．05）；结论本方法简便，快速，特异结合信号较强，费用低；125I-SP的用量是影响其与SP受体特异结合的重要因素。

Functional dissection of parabrachial substrates in processing nociceptive information

Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Similar effects of substance P on learning and memory function between hippocampus and striatal marginal division

Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal di- vision of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neuro- kinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Indepen- dent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addi- tion to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum.

SP/NK-1R系统在乳腺癌中的研究进展

近年来,尽管乳腺癌的治疗已取得诸多进展,但其发病率仍呈上升趋势,寻找新的药物靶点和生物标志物已成为研究热点。越来越多的临床研究开始关注肿瘤细胞与肿瘤微环境的相互作用,认为肿瘤微环境对恶性肿瘤的进展起着至关重要的作用。物质P(Substance P,SP)能够参与癌变过程,在维持肿瘤微环境中发挥着关键作用。NK-1受体(Neurokinin 1 receptor,NK-1R)在肿瘤细胞的细胞质中表达,与诸多肿瘤特征显著相关。SP通过其受体NK-1R诱导肿瘤细胞增殖、血管生成和迁移,并发挥抗凋亡作用。在未来的治疗方案中,能否应用NK-1R拮抗剂为乳腺癌的诊断与治疗提供更精准的靶点成为热点话题。本文就SP/NK-1R系统在乳腺癌中的研究状况进行综述。

调气法针刺联合加巴喷丁治疗带状疱疹后遗神经痛的疗效观察及对血清β-EP和NK-1水平的影响

目的 观察调气法针刺联合加巴喷丁治疗带状疱疹后遗神经痛(postherpetic neuralgia, PHN)的临床疗效及对患者血清β-内啡肽(beta endorphin, β-EP)、神经激肽1-受体(neurokinin-1 receptor, NK-1)和P物质(substance P, SP)水平的影响。方法 将102例PHN患者随机分为对照组及治疗组,每组51例。对照组给予单纯加巴喷丁治疗,治疗组给予调气法针刺联合加巴喷丁治疗。观察两组治疗前后视觉模拟疼痛量表(visual analog scale, VAS)、睡眠状况自评量表(self-rating scale of sleep, SRSS)、汉密顿焦虑量表(Hamilton anxiety scale, HAMA)、世界卫生组织生存质量量表(World Health Organization quality of life assessment,WHOQOL)及血清β-EP、NK-1和SP水平,并比较两组临床疗效。结果 治疗后,两组VAS、SRSS及HAMA评分均低于治疗前(P<0.05),且治疗组VAS、SRSS及HAMA评分低于对照组(P<0.05)。治疗后,两组WHOQOL各维度评分均高于治疗前(P<0.05),且治疗组均高于对照组(P<0.05)。治疗后,两组血清β-EP水平升高(P<0.05),血清NK-1和SP水平降低(P<0.05),且治疗组优于对照组(P<0.05)。治疗组的总有效率为94.1%,高于对照组的82.4%(P<0.05)。结论 调气法针刺联合加巴喷丁治疗PHN疗效较好,可有效减轻患者不适症状,提高生活质量,有效降低血清NK-1、SP水平,升高血清β-EP水平。

土大黄提取物对银屑病小鼠P物质及其神经肽受体-1表达的影响

目的:经土大黄干预,探讨P物质(SP)及其神经激肽-1受体(NK-1R)在银屑病皮肤组织中的表达及意义。方法:收集对照组,银屑病模型组,甲氨蝶呤片组(1.3 mg/kg),阿瑞匹坦胶囊组(5 mg/kg),土大黄组(1、2、4 g/kg)小鼠皮肤、血液标本,经苏木精-伊红(HE)染色,观察银屑病小鼠皮肤组织病理学变化;采用实时荧光定量聚合酶链反应(RT-qPCR)技术,检测银屑病小鼠皮肤SP、NK-1R mRNA表达;采用酶联免疫吸附测定、蛋白免疫印迹技术,检测银屑病小鼠血液SP、皮肤、NK-1R蛋白表达;随后分析SP、NK-1R表达水平与银屑病的关系。结果:与银屑病模型组比较,所有药物干预组均能改善银屑病小鼠皮肤组织病理学变化;同时,小鼠皮肤SP、NK-1RmRNA表达,血清SP、皮肤NK-1R蛋白表达均降低(P<0.05,P<0.01)。与阳性对照药甲氨蝶呤片组、阿瑞匹坦胶囊组比较,1 g/kg大黄组小鼠皮肤组织NK-1R蛋白表达升高(P<0.05)。与土大黄组(1 g/kg)比较,土大黄组(2、4 g/kg)小鼠皮肤组织NK-1R蛋白表达均降低,其中土大黄组(2 g/kg)(P>0.05)、土大黄组(4 g/kg)(P<0.05)。结论:土大黄可能通过降低焦虑相关神经递质SP及其NK-1R受体基因、蛋白表达,从而改善小鼠银屑病样皮损,其作用不亚于阳性对照药甲氨蝶呤片、阿瑞匹坦胶囊。

Localization of P2X_7 Receptor Immunoreactivity in the Dorsal Root Ganglia of Guinea Pig

The P2X7 receptor mRNA and proteins in guinea-pig dorsal root ganglia （DRG） were studied by using RT-PCR and immunohistochemistry. The co-localization of P2X7 receptor with four cytochemical markers, the neurofilament protein NF200, S100, substance P and isolectin t34 （IB4） binding glyco-conjugates, were also examined. It was found that P2X7 receptor immunoreactivity （P2X7 R-IR） was present mostly in large-and medium-sized DRG neurons （62%±9% and 36%±6% respectively in all P2X7 R-IR neurons）. All the P2X7 R-IR neurons were also NF200 and S100 immunopositive. However, in a small number of NF200 or S100 immunopositive neurons no P2XTR-IR was detectable. All the IB4-positive or substance P-immunopositive neurons had no P2X7 R-IR. These results demonstrate that P2X7 receptors are expressed in a large subpopulation of DRG neurons and they may play a role in the transduction of specific peripheral sensory signals.

Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait

Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.

Effect of nonpeptide NK1 receptor antagonist L-703,606 on the edema formation in rats at early stage after deep partial-thickness skin scalding

Objective:To investigate the effect and the relevant potential mechanism of nonpeptide neurokinin 1(NK1) receptor antagonist L-703,606 in the edema formation after burn injury. Method:1.-703,606 treatment was performed in Sprague-Dawley(SD) rats at early stage after deep partial-thickness skin scalding.One hundred and fifty two adult male SI) rats were used in the study and randomly divided into sham scald(SS,n=8),scald control(SC,n=48),and L-703,606 treatment(IT,n=48) groups.The rats in SC and LT groups were subjected to 20%total body surface area(TBSA) deep partial-thickness skin scalding.Modified Evans blue extravasation, tracing electron microscopy by lanthanum nitrate and mean water content assay were employed to observe and detect the changes of vascular permeability,ultrastructure and edema formation in adjacent tissue to the wounds and in the jejuna of rats at early stage(72 h) after scald.Results: The pathological increase of vascular permeability in the periwound tissue and jejunum of rats in LT group were significantly lower than that in SC group(P【0.01),and recuperated earlier. Meanwhile,the changes of water contents of corresponding tissues in LT group were lighter than those in SC group(P【0.01).The ultrastructural changes of the microvessels in the peri-wound tissue of LT group showed that the junctions between microvascular endothelium cells were more narrow than those of SC group,moreover,and the number of opening and the engorgement and cavitation of the vascular endothelium cells decreased,the areosis and edema in perivascular tissue lightened,and the precipitation of the high eletron density lanthanum tracing agent in the interspace of the tissue decreased significantly in LT group.Conclusions:It is concluded that nonpeptide NK1-receptor antagonist L-703,606 could lighten the vascular permeability and edema formation in the periwound tissue and jejunum,and accelerate the normalization process of pathological changes in the tissues of rats after scald.

Distribution of SP receptor in the auditory centre of brainstem and inthe medial geniculate body of guinea pigs

Objective: To investigate the distribution of substance P receptor (SPR) in the brainstem auditorycentre and medial geniculate body (MGB) of guinea pigs. Methods: Rabbit antiserum against SPR, immunohistochemical method and glucose-oxidase-DAB-nickle technique were used in this study. Results:SPR-positiveneurons, fibers and terminals were distributed widely in the cochlear nucleus, superior olive complex,inferiorcolliculus and MGB. In the cochlear nucleus, SPR-positive neurons were distributed mainly in the ventralcochlear nucleus (VCN). SPR-positive products were located predominately on the cell membrane. The density of positive terminals in the dorsal cochlear nucleus (DCN) was higher than that in the ventral cochlear nucleus. The distribution pattern of SPR-positive products in the superior olive complex had distinct characteristics. SPR-positive fibers, terminals and neurons were also found, but the number of positive neurons wasfewer. The density of SPR-positive fibers and terminals in the MGB was quite high. Conclusion:SP may participate in transmitting sound messages in brainstem auditory centre and MGB of the guinea pig.

更年健上调老年雌性大鼠下丘脑雌激素受体mRNA表达对P物质和β-内啡肽的影响

目的：探讨中药复方更年健上调老年雌性大鼠下丘脑雌激素受体（ ＥＲ）和 ＥＲ信使核糖核酸（ｍＲＮＡ）对Ｐ物质（ＳＰ）和β－内啡肽（β－ＥＰ）的影响。方法：建立自然衰老的雌性大鼠模型，用放射配体结合分析法检测 ＥＲ，用 Ｎｏｒｔｈｅｒｎ ｂｌｏｔ分析 ＥＲｍＲＮＡ的改变，用放射免疫分析法检测 ＳＰ和β－ＥＰ含量。结果：老年雌性大鼠性减退期下丘脑 ＥＲ和 ＥＲｍＲＮＡ水平随血清Ｅ_２水平的下降较性成熟期显著下降，而更年健则使下降了的ＥＲ和ＥＲｍＲＮＡ水平明显提高，并通过上调下丘脑ＥＲｍＲＮＡ使ＳＰ明显下降，而β－ＥＰ则显著提高，与提高体内雌激素水平具有同样的效果。结论：更年健可增加ＲＲ在下丘脑的表达以增强雌激素的生物学效应，同时降低下丘脑 ＳＰ水平而提高 β－ＥＰ的含量。

P物质和P物质受体在小鼠胚胎发育期脑内的表达

目的研究小鼠胚脑发育期间P物质(SP)和P物质受体(SPR)的表达。方法分别取孕11、13、15、17和19d的小鼠胚脑和新生鼠脑,采用SP和SPR酶标免疫组织化学染色观察SP和SPR表达的变化。结果SP自小鼠胚胎11d开始出现少量表达,并一直持续到出生后,主要出现在发育过程中的新纹状体等部位;SPR与SP同时出现并持续到出生后,主要出现在发育过程中的延髓中缝等部位。结论SP和SPR在小鼠发育期间的表达提示SP可能参与中枢神经系统神经元形成和成熟调控。

人参皂甙-Rd对SNI大鼠痛敏异常及脊髓背角内P物质和NK-1受体表达的影响

目的:观察人参皂甙-Rd(Ginsenoside-Rd,G-Rd)对坐骨神经分支选择损伤(spared nerve injury,SNI)大鼠痛敏异常及脊髓背角内P物质(substance P,SP)和NK-1受体表达的影响,进而探讨G-Rd镇痛的脊髓机制。方法:成年雄性SD大鼠(30只)随机分成五组:空白对照组(blank control)、假手术组(sham operation)、坐骨神经分支选择损伤组(spared nerve injury,SNI)、SNI+saline(腹腔注射,i.p.)组、SNI+G-Rd(i.p.)组。行为学采用von Frey法测定上述各组手术侧机械缩足反射阈值(paw withdrawal mechanical thresholds,PWMT);用免疫荧光组织化学染色法检测对比上述各组大鼠脊髓L4-6节段背角内SP免疫荧光产物的荧光强度和NK-1阳性细胞的数量。结果:SNI术后10 d,大鼠手术侧PWMT值明显低于正常对照组和假手术组,术后20 d到达最低值;而在SNI+G-Rd组PWMT值则明显高于SNI组和SNI+sline组(P<0.05)。免疫荧光染色结果显示:术后20 d时,SNI组和SNI+saline组的脊髓手术侧L4-6背角内SP样免疫荧光的强度和NK-1样阳性细胞的数量明显有所增高,与对照组和假手术组相比较具有显著性意义(P<0.05);但SNI+G-Rd组与SNI组和SNI+saline组相比,其SP样免疫荧光的强度和NK-1样阳性细胞的数量则明显有所下降(P<0.05)。结论:人参皂甙-Rd抑制神经病理性疼痛的机制之一可能与有效减少脊髓背角内SP和NK-1受体的表达有关。