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.

Serotonin样,Substance P样,Enkephalin样反应阳性神经元胞体在大鼠中缝核簇内的分布

本文用PAP法研究了Serotonin样,Substance P样,Leucine—Enkephalin样和Methionine—Enkephalin样反应阳性神经元胞体在大鼠中缝核簇内的分布。证明Serotonin存在于中缝苍白核、中缝隐核、中缝大核、中缝桥核、中央上核和中缝背核等处的某些神经元胞体内。以中、小细胞为主,在中缝大核内有少数大细胞。细胞形态为梭形、圆形、卵圆形以及多极细胞。Substance P样反应阳性胞体在上述中缝核内也被发现,其胞体的大小、形态和分布与serotonin样反应阳性胞体相似,但数目稍少。Leucine—Enkephalin样反应阳性胞体存在于中缝苍白核、中缝隐核、中缝大核、中缝桥核、中缝背核和中央上核内,但Methionine—Enkephalin样反应阳性细胞体仅在中缝苍白核和中缝隐核的吻侧部以及中缝大核内发现。后两者均以大,中型多极细胞为主。

Magnesium effects on behavior and substance P mRNA expression in the midbrain of a rat migraine model

BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE： To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model, and to determine the action pathway of migraine treatment using magnesium. DESIGN, TIME AND SETTING： A completely randomized, controlled, animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS： Magnesium sulfate （25%） was supplied by Tianjin Pharmaceutical Jiaozuo, China. Nitroglycerin was provided by Shanxi Kangbao Biological, China. Substance P primer sequence was synthesized by TaKaRa Biotechnology （Dalian）, China. METHODS： A total of 36 healthy, adult, Wistar rats were randomly assigned to 6 groups： control, migraine, low- and high-dose magnesium sulfate treated, and low- and high-dose magnesium sulfate control, with 6 rats in each group. Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups. Five minutes following administration, rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate, while those in high-dose groups were injected with 300 mg/kg magnesium sulfate. No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES： At 2 hours after nitroglycerin injection, substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction. At 60-90 minutes after nitroglycerin injection, behavioral changes of pain were analyzed in the experimental rats. RESULTS： The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group （P 〈 0.05）. Following magnesium sulfate injection, substance P mRNA expression increased, compared with the migraine and control groups （P 〈 0.05）. In the low- and high-dose magnesium sulfate treated groups, pain behavior was remarkably ameliorated, compared with the migraine group （P 〈 0.05）, particularly with the high-dose injection （P 〈 0.05）. CONCLUSION： Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner, and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.

神经肽类似物DOTA-Substance P的^(177)Lu标记及其生物分布

为探讨神经肽类药物177 Lu-DOTA-Substance P(以下简称为177 Lu-DOTA-SP)用于人胰腺癌PANC-1的肿瘤显像及治疗的可能性,研究了DOTA-SP的177 Lu标记;考察了177 Lu-DOTA-SP在室温下生理盐水中与在37℃小牛血清中的稳定性;评价了177 Lu-DOTA-SP在正常昆明小鼠与人胰腺癌PANC-1模型裸鼠体内的生物分布特点,并对人胰腺癌PANC-1模型裸鼠进行了SPECT显像研究。结果表明,在优化条件下,DOTA-SP的177 Lu标记率>90%,纯化后,177 Lu-DOTA-SP的放化纯度>98%。177 Lu-DOTA-SP在生理盐水与5%小牛血清中显示了良好的稳定性,与浓度较高的血清(10%)竞争反应时,其降解稍快。177 Lu-DOTA-SP在正常昆明小白鼠体内的生物分布特点为:血清除快,肾放射性摄取高且滞留时间长;骨中有一定放射性摄取,且滞留长。177 Lu-DOTA-SP在人胰腺癌PANC-1模型裸鼠中的体内分布结果表明,肿瘤细胞中放射性摄取在给药后不同时间点均高于正常胰腺细胞中的放射性摄取,提示在PANC-1肿瘤细胞中有NK-1受体存在。SPECT显像结果显示,177 Lu-DOTA-SP在肿瘤细胞中放射性浓集并不明显。177 Lu-DOTA-SP应用于胰腺癌肿瘤显像与治疗的价值尚需进一步研究。

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.

Extracellular signal-regulated kinase, substance P and neurokinin-1 are involved in the analgesic mechanism of herb-partitioned moxibustion

Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu （ST25） and Qihai （CV6） points were selected for herb-partitioned moxi- bustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance E and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.

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.

EFFECT OF CAPSAICIN ON SUBSTANCE P IN PSORIASIS VULGARIS

Objective To the investigate the mechanism of capsaicin in psoriasis vulgaris. Methods Substance P(SP) in psoriatic lesions before and 6 weeks after the treatment with capsaicin was detedted by radioimmunoassary. Results After 3 weeks and 6 weeks treatment with capsaicin, SP in psoriatic lesions was decreased ( P <0.05), while it in the self control group was not decreased; Overall the efficient incidence in therapeutic group was 78.8% , while it in the control group was 36.8% . There was significant difference between them (χ 2 =16.30, P<0.001). Conclusion Capsaicin inhibits dermal inflammatory responses and proliferation of keratinocytes by decreasing the expression of SP in psoriasis vulgaris.

Substance P combined with epidermal stem cells promotes wound healing and nerve regeneration in diabetes mellitus

Exogenous substance P accelerates wound healing in diabetes,but the mechanism remains poorly understood.Here,we established a rat model by intraperitoneally injecting streptozotocin.Four wounds（1.8 cm diameter） were drilled using a self-made punch onto the back,bilateral to the vertebral column,and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds.With the combined treatment the wound-healing rate was 100% at 14 days.With prolonged time,type I collagen content gradually increased,yet type III collagen content gradually diminished.Abundant protein gene product 9.5-and substance P-immunoreactive nerve fibers regenerated.Partial nerve fiber endings extended to the epidermis.The therapeutic effects of combined substance P and epidermal stem cells were better than with amniotic membrane and either factor alone.Our results suggest that the combination of substance P and epidermal stem cells effectively contributes to nerve regeneration and wound healing in diabetic rats.

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.

鸡脊髓背角胶状质中calbindin-D28k阳性终末的超微结构及与substance P阳性终末之间的联系

目的观察鸡脊髓背角胶状质中calbindin-D28k(CB)阳性终末的超微结构及其与含有substance P(SP)中央末梢之间的联系。方法应用免疫电镜技术观察鸡脊髓背角胶状质中CB阳性终末的超微结构,并应用激光共聚焦显微镜观察鸡脊髓背角胶状质中CB和SP阳性突触小球中央末梢之间的关系。结果电镜下观察:1)突触小球中含有心小泡的中央末梢呈CB免疫阳性;2)突触小球内或外的部分含小泡的树突呈CB免疫阳性;以及3)突触小球外的部分轴突呈CB免疫阳性。在突触结构内,CB免疫阳性反应物主要分布于突触后膜上。免疫荧光双标记法显示,SP阳性的含有心小泡的中央末梢呈CB阳性。结论突触小球的中央末梢中CB与SP共存,提示CB可能通过其钙离子缓冲作用,参与脊髓的痛觉调制。

Substance P mRNA expression in the rat spinal cord following selective brachial plexus injury

BACKGROUND： The neuropeptide, substance P, has various bioactivities and is widely distributed in the central nervous system. Substance P participates in neural transmission in the spinal cord and plays an important role in regeneration and repair of nerve injury. OBJECTIVE： To investigate substance P mRNA expression in the anterior horn of the spinal cord following brachial plexus injury. DESIGN, TIME AND SETTING： A molecular cell biology randomized controlled study was performed at the Department of Anatomy, Zhongshan Medical College, Sun Yat-sen University and the DaAn Gene Laboratory in May 2005. MATERIALS： A total of 29 adult male Sprague Dawley rats were randomly assigned to a control group （n = 5） and an injury group （n = 24）. METHODS： The injury group was divided into three subgroups. In subgroup A, the right seventh cervical vertebra （C7） anterior root was avulsed, and the residual nerve root at the distal end was removed. In subgroup B, the right C7 anterior root was avulsed, and the right C5 first thoracic vertebrae （T1） posterior root was incised. Thus afferent pathways of the posterior root that connected with the anterior horn motor neurons were blocked. In subgroup C, the right C7 anterior root was avulsed, and a right C56 hemisection was performed. Thus the descending fiber pathways of the cortex that connected with anterior horn motor neurons were blocked. In the control group, the C5-T1 vertebral plate was opened, and then the skin was sutured. MAIN OUTCOME MEASURE： Substance P mRNA expression in the anterior horn of the spinal cord was quantified using fluorescent quantitative reverse transcription-polymerase chain reaction. RESULTS： Substance P mRNA expression was low in the anterior horn of the rat spinal cord in the control group. Substance P mRNA expression in the anterior horn of the spinal cord was upregulated and was significantly higher in the injury group compared with the control group （P 〈 0.01）. Substance P mRNA expression was highest in subgroup B. CONCLUSION： Brachial plexus anterior root avulsion is responsible for increased substance P expression in the anterior horn of the rat spinal cord. Pathway disjunction in efferent fibers of the posterior root or cortex does not have an effect on substance P expression in the anterior horn of the spinal cord.

STUDIES ON THE RELATIONSHIP BETWEEN SUBSTANCE P AND ABNORMAL GASTROINTESTIANL TRANSIT

Objective To realize the relationship between substance P(SP) and abnormal gastrointestinal transit.Methods By radioimmunoassay, concentration of SP in sigmoid mucosa was determined in 12 healthy volunteers, 15 slow and 10 fast transit patients.Results The concentration was (27.68±15.42)μg/g,(24.07±5.76)μg/g and (28.61±18.34)μg/g,respectively.They had no statistical difference.Conclusion There was no relationship between concentration of SP in sigmoid mucosa and abnormal gastrointestinal transit.

^(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。

Tong xie yao fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P

AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of 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.

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 (EA) 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 signif icantly 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 signif icantly 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.

Effects of morphine and electroacupuncture on substance P level in spinal cord and their relation to pain threshold in rats

Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injection of mor-phine(7.5mg/kg)or electroacupunctured(3V and 3Hz)on the “Jiaji point”.It wasfound that the pain threshold(PT),Ir-SP level and SP-Li in the dorsal horn of the spi-nal cord were more significantly increased in the animals after the administration ofmorphine or electroacupuncture than in the control(P【0.05～0.01).The combined effectsof morphine and electropacupuncture were even more powerful than either of the agentswas administered singly.Naloxone could block the analgesic effect and the elevation ofIr-SP due to morphine or electroacupuncture.The findings suggest that there is a synergismbe tween morphine and electroacupuncture and the analgesic effect of the 2 depends uponthe increase of Ir-SP level of the spinal cord mediated through the opiate receptors.

Morphological characteristics of the synaptic structures of substance P-immunoreactive terminals in the marginal division of the rat striatum

In the present study,the morphological characteristics of the synaptic structure(MCSS)of the substance P immunoreactive(SPIR)teminals in the marginal division(MrD)of the ratstriatum were studied by using electron microscopy and immunocytochemistry.Four major typesof SPIR symnapses were identified in teh MrD.axodendritic,axo-spinous,axo-axonic,and com-pound.Axo-dendritic and axo-spinous synapses were more common,and a few axo-axonic andcompound synapses wer observed as well.In the postsynaptic target zones of axo-dendritic,andaxo-spinous synapses,there were small or large dendrites or spires.Some synapses with morethan two synaptic components are referred to as compound synapses.Both symmetric andasymmetric SPIR synapses were seen in the MrD.The vesicles in the SPIR presynaptic boutonswere mostly pleomorphic although a few of them were round,The MCSS distinguishes theultrastructure of the MrD from that of the other part of striatum,which suggests that the func-tion of the MrD may be different from that of the rest of the striatum.

Relationship between Dysphagia and Serum Substance P Level in Chronic Central Nervous Disease

Purpose: We compared serum substance P (SP) levels in underlying diseases and dysphagia, or its absence, in patients with cerebrovascular disease, neurodegenerative disease or Alzheimer’s disease, to investigate the relationship between dysphagia and serum SP in chronic central nervous disease. Methods: Subjects comprised 94 patients admitted to a hospital or nursing home during the 5 years between April 2007 and April 2012 with central nervous symptoms. Serum SP levels were measured by enzyme immunoassay, and video endoscopy using a nasal endoscope in all subjects to objectively evaluate swallowing function. Results: Serum SP level was very similar in central nervous disease without dysphagia and controls without central nervous disease. Conversely, serum SP level was significantly lower in central nervous disease with dysphagia. When comparing underlying diseases, serum SP was significantly lower in Parkinson’s disease than in other disease groups (cerebrovascular disease, Alzheimer’s disease). Looking at changes in serum SP levels over time after disease onset, SP level was significantly low in subjects without dysphagia at the time of onset who went on to develop dysphagia during the disease course, whereas serum SP level tended to be higher in subjects with dysphagia at the time of onset and improvement during the disease course. With Parkinson’s disease and cerebrovascular disease, serum SP was low, particularly in subjects thought to have severe damage to the basal ganglia. Conclusion: Serum SP is generally thought to decrease in patients with cerebrovascular disease accompanied by dysphagia, but these results suggest that serum SP levels can be expected to improve to some extent, even if dysphagia is present at disease onset, assuming, for example, that some basal ganglia function remains. Positive therapeutic interventions such as swallowing rehabilitation should be promoted in such patients, with the goal of improving swallowing function.