Dual role of osteoblastic proenkephalin derived peptides in skeletal tissues

Proenkephalin encodes a group of small peptides with opiate-like activity, the endogenous opioids, known to function as neurohormones, neuromodulators, and neurotransmitters. Recently, we have demonstrated that in addition to its abundance in fetal brain tissue, proenkephalin is highly expressed in nondifferentiated mesodermal cells of developing fetuses. We identified the skeletal tissues, bone, and cartilage as major sites of proenkephalin expression. To examine the possibility that proenkephalin is involved in bone development we have studied the expression of this gene in bone-derived cells, its modulation by bone active hormones, and the effects of enkephalin-derived peptides on osteoblastic phenotype. Our studies revealed that osteoblastic cells synthesize high levels of proenkephalin mRNA which are translated, and the derived peptides are secreted. Reciprocal interrelationships between osteoblast maturation and proenkephalin expression were established. These results together with our observations demonstrating inhibitory effects of proenkephalin-derived peptides on osteoblastic alkaline phosphatase activity, strongly support the notion that proenkephalin is involved in bone development. A different direction of research by other investigators has established the capability of the opioid system in the periphery to participate in the control of pain. On the basis of these two lines of observation, we would like to present the following hypothesis: The potential of embryonic skeletal tissue to synthesize proenkephalin-derived peptides is retained in the adult in small defined undifferentiated cell populations. This potential is realized in certain situations requiring rapid growth, such as remodeling or fracture repair. We suggest that in these processes, similarly to the situation in the embryo, the undifferentiated dividing cells produce the endogenous opioids. In the adult these peptides may have a dual function, namely participating in the control of tissue regeneration and in the control of pain. © 1994 Wiley-Liss, Inc.     

左旋四氢巴马汀加强电针对兔大脑皮层牙髓诱发电位的抑制作用

家兔6只,用氨基甲酸乙酯和氯醛糖麻醉,电刺激牙髓,在对侧大脑皮层体感Ⅰ区引导其诱发电位,观察诱发电位各成分与痛的关系。结果观察到,在P1、N1、P2和 N2 4个波中,P1和 P2波相对稳定。其中,P2波(波峰潜伏期:66.1±1.9ms)具有较高的阈值,且不受无镇痛作用的中枢抑制剂安定的影响,而受小剂量镇痛剂度冷丁的抑制,提示 P2波与痛有关。以 P2波的波幅为指标,进一步在12只家兔上观察了 L-THP 和电针及两者合用对诱发电位的影响。结果显示,L-THP 和电针对诱发电位均有抑制作用,且两者在作用强度和时间上存在明显的协同,提示 L-THP 具有加强电针对兔大脑皮层牙髓诱发电位中痛相关成分的抑制作用。     

压脚痛阈测定法的改进和应用

本文介绍一种改进的压脚测痛法。采用电机驱动替代用手挤压橡皮球完成升压过程;通过一个自动的电路切断结构判定抽脚反应,较目视更加客观;用读数保持电路记录压力变化,较直接读取刻度值更加准确,可靠。这些优点,业经电针和吗啡镇痛实验验证。     

家兔中脑导水管周围灰质中甲七肽样免疫活性物质具有镇痛作用并参与电针镇痛

以辐射热照射家兔鼻嘴部皮肤,测定甩头反应潜伏期(ERL)作为痛阈。通过预先埋植的慢性套管向中脑导水管周围灰质(PAG)注射甲七肽降解酶抑制剂 Captopril,观察其镇痛作用以及加强电针镇痛的作用能否被特异的甲七肽抗血清所对抗。(1)单侧 PAG 注射 Captopril240 nmol 的镇痛作用可为同一部位注射甲七肽抗血清(1μl)所翻转,注入甲啡肽抗血清则无效。(2)单侧 PAG 注射 Captopril 60 nmol 有加强电针镇痛的作用。该作用可被1μl 甲七肽抗血清所完全取消,将抗血清量减少到0.1μl 则无效。以上结果说明 PAG 内的甲七肽样免疫活性物质在镇痛和电针镇痛中发挥重要作用。     

家兔中脑导水管周围灰质中注射八肽胆囊收缩素(CCK-8)拮抗吗啡镇痛和电针镇痛

家兔单侧PAG内注射CCK-83ng,能使静脉注射4mg/kg吗啡引起的镇痛作用降低73％或使电针镇痛效果降低67％。在1.5—6.0ng范围内呈量效关系。无硫的CCK-8无此作用。PAG内注射CCK受体拮抗剂proglumide 4μg可翻转CCK-8的抗吗啡镇痛作用。说明PAG部位注射外源性CCK-8可通过CCK受体对抗阿片镇痛。 PAG内注射CCK-8抗血清可显著增强静脉注射2mg/kg吗啡的镇痛效果。PAG内注射CCK抗血清本身也能引起痛阈轻度升高。说明PAG内有内源性的CCK-8发挥紧张性的抗阿片镇痛作用。     

福尔马林致痛提高大鼠中枢μ阿片受体密度及电针的加强作用

用放射自显影方法观察到;（１）大鼠脚掌注射福尔马林后,某些与镇痛有关的脑区如尾核头部、伏隔核、杏仁核、中央灰质、脚间核、中缝大核、脊髓背角等结构中μ阿片受体密度明显增加（Ｐ＜０．０５,Ｐ＜０．０１）;（２）给予电针抑制痛反应的大鼠,在其大部分上述结构及扣带回、隔区、视前内侧区、内膝体、上丘、中缝背核及中央上核受体密度明显增加;与福尔马林注射组相比,脚间核、中央灰质尾端腹外侧区、腰膨大背角的受体密度进一步增加。从而在受体水平支持伤害性刺激可以激活体内内阿片肽能活动,而电针可以加强这一活动的设想。     

Evidence for an in vivo and in vitro modulation of endogenous cortical GABA release by α-glycerylphosphorylcholine

The effects of α-glycerylphosphorylcholine (α-GPC) on endogenous cortical GABA release were studied both in vivo and in vitro. In freely moving rats, equipped with epidural cups, α-GPC (30–300 mg/kg i.p.) increased GABA release. This effect was potentiated by atropine, both systematically administered (5 mg/kg i.p.) and locally applied (1.4 μM), but not by mecamylamine (4 mg/kg i.p.). The α-GPC-induced increasein GABA release was abolished in rats pretreated with the α₁ receptor antagonist prazosin (14 μg/kg i.p.). In cortical slices α-GPC (0.4 mM) increased the spontaneous GABA efflux. This effectwas abolished by tetrodotoxin (0.5 μM) and prazosin (1 μM), but not by atropine (0.15 μM) ormecamylamine (2.5μM). These results indicate that the facilitatory response by α-GPC on GABArelease does not depend on a direct activation of either muscarinic or nicotinic receptors, but suggest the involvement of the noradrenergic system.     

大鼠杏仁核内注射八肽胆囊收缩素（CCK—8）拮抗吗啡镇痛的研究

大鼠双侧杏仁核内注射ＣＣＫ－８１ｎｇ（１μｌ）,能明显降低皮下注射４ｍｇ／ｋｇ吗啡产生的镇痛作用,并在０．１－１ｎｇ范围内呈量效关系。分别向双侧仁核注射ＣＣＫ－Ａ受体拮抗剂Ｄｅｖａｚｅｐｉｄｅ５０ｎｇ能部分翻转,２００ｎｇ则完全翻转ＣＣＫ－８的抗吗啡镇痛作用,１０ｎｇ无效;而ＣＣＫ－Ｂ受体拮抗剂Ｌ－３６５,２６０在５－８ｎｇ时即可完全番转ＣＣＫ－８的抗吗啡镇痛作用。杏仁核注射２００ｎｇ的Ｄｅｖａｚ     

The Ethanol Extract of Syringa oblata Heartwood,a Mongolian Folk Medicine Containing Major Lignans,Exerts Analgesic and Sedative Effects on Mice

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.     

催产素在脊髓水平对电针镇痛的影响

采用玻璃微电极胞外记录和脊髓表面给药的方法观察了催产素（ＯＴ）、抗催产素血清（ＡＯＴＳ）以及电针穴位对背角神经元伤害性诱发放电的影响。结果表明：电针穴位或脊髓表面施加ＯＴ可部分抑制脊髓背角神经元的伤害性诱发放电;在电针的基础上施加ＯＴ则明显加强电针的抑制效应;相反,用ＡＯＴＳ预处理后,电针的抑制作用放取消。提示ＯＴ在脊髓水平参与了对痛觉信息的调制,并与一定频率的针刺镇痛有关。