黑质在痛觉调制中的作用

黑质属于锥体外系,与躯体运动有关。近年来的资料表明,黑质也参与痛觉调制,它可能是下行性镇痛系统的重要组成部分;也有学者认为黑质对痛觉信息的上传有易化作用。本文简述了黑质的结构特征,纤维联系及在痛觉调制中的作用等方面的研究进展。     

生长抑素对脊髓P物质痛觉传递的抑制作用

本研究应用痛阈测定及免疫组化法,探讨生长抑素对脊髓Ｐ物质痛觉调制作用的影响。结果表明,鞘内注射（ｉｔ）ＳＳＴ（１０μｇ）可使痛阈提高,并可抑制ＳＰ引的反应应及脊髓ｃ－ｆｏｓ表达。     

痛觉和痛觉的调制

本文首先简单地介绍了关于痛觉的三种学说,并加以讨论。特异学说肯定了痛觉传递有自己的神经通路,这大体上是正确的,但我们不应把这种通路看成是刻板不变的。型式学说着重“传入冲动的空间和时间构型是传递信息的重要方式”这一点是为人们所接受的,但它忽视感觉末梢的机能分化是受到责难的。闸门学说把痛觉的传递和对痛觉的调制作为一个整体来考虑,这是可取的,虽然它的细节已有很大的修改。本文着重介绍了近十余年来九个方面的进展,其中最重要的可能是特异的痛感受器和痛敏神经元的发现、电刺激脑镇痛和内源性吗啡样物质的发现。关于针刺镇痛的研究也是重要的进展,但本文未予讨论。     

外侧网状旁巨细胞核在痛觉调制系统中的地位和作用

外侧网状旁巨细胞核是位于延髓头端腹外侧区网状结构中的一个核团,具有显著的镇痛作用。它与镇痛有关核团具有广泛的纤维联系,如中脑导水管周围灰质、中缝大核,网状外侧核等。该核团的多种递质如内阿片肽,去甲肾上腺素,γ－氨基丁酸等均参与其痛觉调制机制。目前认为,ＲＰＣＬ是内源性痛觉调制系统的很重要的组成部分。     

一氧化氮与痛觉调制

大量证据表明一氧化氮（ＮＯ）参与外周及中枢水平的痛觉调制：在外周,ＮＯ表现为致痛和镇痛双重作用;在中枢,ＮＯ不但可以促进脊髓水平痛觉过敏的形成和发展,而且参与脑内的致痛作用。     

前扣带回及其情感性痛觉调制

前扣带回(ACC)是端脑边缘系统的重要结构,参与包括情感性痛觉在内的多种生理功能的调制.ACC与前额叶皮质、顶叶皮质、丘脑、杏仁体、伏隔核、下丘脑和脑岛前区等痛觉处理相关结构具有密集而复杂的纤维联系.阿片类神经肽及其μ、δ、κ受体、兴奋性氨基酸如谷氨酸及其NMDA、AMPA、KA等受体在情感性痛觉处理过程中发挥重要作用.     

腹外侧眶皮层在痛觉调制和针刺镇痛中的作用

腹外侧眶皮层 (ventrolateral orbital cortex, VLO) 是眶皮层的主要成分,它与导水管周围灰质(PAG)、丘脑和其它皮层之间有广泛的纤维联系.VLO不仅是一个痛觉感受中枢,而且也是一个痛觉调制中枢,通过激活PAG脑干下行抑制系统在脊髓和三叉水平抑制伤害性信息的输入.研究还证实,阿片、 5-HT和GABA等神经递质及其受体参与VLO的抗伤害效应.此外,VLO在针刺镇痛中也发挥重要作用.本文就腹外侧眶皮层在痛觉调制和针刺镇痛中的作用进行综述.     

痛觉的脑功能成像研究进展

本文综述了近年来关于痛觉功能性脑成像的研究进展,痛觉的感觉辨别成分似与外侧丘脑、初级和次级躯体感觉区及岛叶皮层有关,而伤害性信息的认知－注意过程则与顶叶后部和前额中皮层有关。扣带回的不同部分调节着痛觉认知和情感的不同方面。文章最后对临床各种疼痛特别是神经源性痛病人的成像研究进行了分析。     

孤啡肽在痛和痛觉调制方面的研究进展

孤啡肽是新近发现的一种结构与功能均与已知阿片肽有所不同的全新的神经肽,有关其在痛和痛觉调制方面的研究是当前神经科学研究的一个热点。本文对孤啡肽在脊髓上（脑）区的抗阿片作用,在脊髓的抗伤害或痛觉过敏作用,以及在吗啡和电针耐受形成方面的作用等研究现状作一综述,以期对孤啡肽的进一步深入研究起到促进作用。     

cAMP应答元件结合蛋白与痛觉调制

cAMP应答元件结合蛋白（cAMP response element binding protein,CREB）是刺激诱导的一种转录因子,通过磷酸化实现调节转录功能。疼痛和痛觉过敏是组织损伤或炎症时常伴有的生理病理过程,谷氨酸、P物质等神经递质或神经肽以及细胞内的信号转导途径参与此过程。近年来研究发现CREB通过自身磷酸化,在炎症、神经损伤等诱发的自发性疼痛、痛觉过敏及痛觉超敏中具有重要作用。本文从CREB的一般特性及其在脊髓水平的痛觉调制中的作用等方面予以综述。     

电刺激和损毁丘脑中央下核对大鼠福尔马林诱发伤害性行为的影响

本文旨在研究丘脑中央下核（thalamic nucleus submedius,Sm）是否参与持续伤害感受性调制。以自动运动检测系统记录大鼠一侧后爪皮下注射福尔马林诱发的伤害性行为（烦乱反应）为指标,观察电刺激和电解损毁Sm对烦乱反应的效应。结果显示,电刺激（100μA,5min）同侧或对侧Sm明显抑制福尔马林诱发的第二时相的烦乱反应,而刺激Sm外邻近结构（超过0．5mm）对烦乱反应无明显效应。电解损毁双侧Sm对第一或第二时相的烦乱反应均无影响。结果提示,Sm不仅参与急性时相性伤害感受性调制,也参与持续性伤害感受性调制。本研究为Sm参与下行痛调制提供了新的证据。     

Brain mechanisms of pain affect and pain modulation

Recent animal studies reveal ascending nociceptive and descending modulatory pathways that may contribute to the affective-motivational aspects of pain and play a critical role in the modulation of pain. In humans, a reliable pattern of cerebral activity occurs during the subjective experience of pain. Activity within the anterior cingulate cortex and possibly in other classical limbic structures, appears to be closely related to the subjective experience of pain unpleasantness and may reflect the regulation of endogenous mechanisms of pain modulation.     

尾核阿片μ受体参与电针及皮层SmⅠ区对束旁核伤害性反应的抑制

为探索尾核（ｃａｕｄａｔｅｎｕｃｌｅｕｓ,Ｃｄ）是否参与电针及皮层体感运动Ⅰ区（ｓｅｎｓｏｒｉｍｏｔｏｒａｒｅａⅠｏｆｔｈｅｃｅｒｅｂｒａｌｃｏｒｔｅｘ,ＳｍⅠ）对束旁核（ｐａｒａｆａｓｃｉｃｕｌａｒｎｕｃｌｅｕｓ,Ｐｆ）神经元伤害性反应的调节,以及Ｃｄ中阿片受体是否参与并通过何种受体参与这一调节,本实验用Ｃｄ头部化学毁损及微量注射阿片受体拮抗剂的方法,观察到Ｃｄ毁损前电针及兴奋皮层均可抑制Ｐｆ的伤害性反应,而毁损后这种抑制效应消失;注射纳洛酮或阿片μ受体拮抗剂βＦＮＡ后,电针及兴奋皮层ＳｍⅠ区对Ｐｆ伤害性反应的抑制作用被取消,而分别注射δ和κ受体拮抗剂ＩＣＩ１７４,８６４和ｎｏｒＢＮＩ则不产生影响。基于已证明大脑皮层参与电针对Ｐｆ伤害性反应的调节,本结果提示：Ｃｄ参与针刺镇痛中皮层ＳｍⅠ区对Ｐｆ神经元伤害性反应的抑制,Ｃｄ中阿片肽主要通过μ受体参与抑制作用。     

杏仁核参与疼痛情绪过程的研究进展

本文综述了近年来关于杏仁核参与疼痛过程的研究进展。疼痛伴随有强烈的情绪反应,而杏仁核是情绪调控中的一个关键核团。最近,越来越多的证据支持杏仁核参与痛觉的编码和调制过程。杏仁核对来自脊髓和三叉神经核的伤害性信息及皮层和丘脑的多种感觉信息进行整合,产生负性情绪,并对疼痛刺激作出相应的行为反应。同时,杏仁核也通过与导水管周围灰质、延髓头端腹内侧区及其它脑干核团的纤维联系参与镇痛过程。     

Cellular distribution and bioactivity of the key steroidogenic enzyme,cytochrome P450side chain cleavage,in sensory neural pathways

Neurosteroids are steroids produced within the nervous system. Based on behavioural responses evoked in animals by synthetic steroid injections, several studies suggested neurosteroid involvement in important neurophysiological processes. These observations should be correlated only to neuroactive effects of the injected steroids. Neurosteroids mostly control the CNS activity through allosteric modulation of neurotransmitter receptors within concentration ranges used by neurotransmitters themselves. Therefore, neurosteroid production within pathways controlling a neurophysiological process is necessary to consider neurosteroid involvement in that process. Because of the increasing speculation about pain modulation by neurosteroids based on pharmacological observations, we decided to clarify the situation by investigating neurosteroidogenesis occurrence in sensory pathways, particularly in nociceptive structures. We studied the presence and activity of cytochrome P450side chain cleavage (P450scc) in rat pain pathways. P450scc-immunoreactive cells were localized in dorsal root ganglia (DRG), spinal cord (SC) dorsal horn, nociceptive supraspinal nuclei (SSN) and somatosensory cortex. Incubation of DRG, SSN or SC tissue homogenates with [3H]cholesterol yielded the formation of radioactive metabolites including [3H]pregnenolone of which the synthesis was reduced in presence of aminogluthetimide, a P450scc inhibitor. These first neuroanatomical and neurochemical results demonstrate the occurrence of neurosteroidogenesis in nociceptive pathways and strongly suggest that neurosteroids may control pain mechanisms.     

Galanin receptors possibly modulate the obesity-induced change in pain threshold

Pain threshold may be up-regulated or down-regulated according to gender, age, race/ethnic and psychological state. Previous studies indicated that obesity may change pain threshold, both nociceptive and antinociceptive, which resulted from obesity-reduced variation of neuroendocrine. However there is a limited understanding of its molecular mechanism underlying this variation. A lot of evidence supports that galanin increases food intake and body weight to induce obesity in animals. This peptide may also modulate nociceptive susceptibility via central galanin receptor 1 and peripheral galanin receptor 2 in dorsal root ganglion. Whereas injury and obesity may up-regulate the galanin expression and stimulate its secretion to elevate the plasma levels of subjects. Pain may increase the risk of obesity through reduced physical activity. In this review, we highlighted the multiple bilateral interrelation between obesity and pain sensitivity, between galanin and obesity and between galanin and injure-induced pain. In view of the above, we reasoned that galanin receptors possibly participated in the modulation of the obesity-induced change in pain threshold, which need further direct evidence to support as yet. This review is helpful to explore the mechanism that galanin receptors regulate the obesity-induced change of pain sensitivity and to contribute to our understanding of the relation among galanin, obesity and pain threshold.     

Interactive responses of a thalamic neuron to formalin induced lasting pain in behaving mice

Thalamocortical (TC) neurons are known to relay incoming sensory information to the cortex via firing in tonic or burst mode. However, it is still unclear how respective firing modes of a single thalamic relay neuron contribute to pain perception under consciousness. Some studies report that bursting could increase pain in hyperalgesic conditions while others suggest the contrary. However, since previous studies were done under either neuropathic pain conditions or often under anesthesia, the mechanism of thalamic pain modulation under awake conditions is not well understood. We therefore characterized the thalamic firing patterns of behaving mice in response to nociceptive pain induced by inflammation. Our results demonstrated that nociceptive pain responses were positively correlated with tonic firing and negatively correlated with burst firing of individual TC neurons. Furthermore, burst properties such as intra-burst-interval (IntraBI) also turned out to be reliably correlated with the changes of nociceptive pain responses. In addition, brain stimulation experiments revealed that only bursts with specific bursting patterns could significantly abolish behavioral nociceptive responses. The results indicate that specific patterns of bursting activity in thalamocortical relay neurons play a critical role in controlling long-lasting inflammatory pain in awake and behaving mice.     

内源性下行抑制/易化系统与5-羟色胺对脊髓伤害感受性信息的调制

内源性下行抑制系统在痛传递与调制中具有重要作用。近年来,与这一系统相对的下行易化系统开始引起人们的关注。中枢神经系统通过下行抑制易化系统对外周伤害性信息进行双向调制。５－羟色胺（５－ＨＴ）是痛上行调制系统的主要神经递质,电刺激或微量注射兴奋性氨基酸于中缝大核（ＮＭＲ）或巨细胞网状核（ＮＧＣ）内,既可兴奋也可抑制脊髓伤害性反应。这种相互矛盾遥效应可能与脊髓内的多种５－ＨＴ受体亚型有关。     

Neurotensin and pain modulation

Neurotensin (NT) can produce a profound analgesia or enhance pain responses, depending on the circumstances. Recent evidence suggests that this may be due to a dose-dependent recruitment of distinct populations of pain modulatory neurons. NT knockout mice display defects in both basal nociceptive responses and stress-induced analgesia. Stress-induced antinociception is absent in these mice and instead stress induces a hyperalgesic response, suggesting that NT plays a key role in the stress-induced suppression of pain. Cold water swim stress results in increased NT mRNA expression in hypothalamic regions known to project to periaqueductal gray, a key region involved in pain modulation. Thus, stress-induced increases in NT signaling in pain modulatory regions may be responsible for the transition from pain facilitation to analgesia. This review focuses on recent advances that have provided insights into the role of NT in pain modulation.     

刺激中缝背核对大鼠脊髓背角神经元伤害性反应的影响及其传出途径的分析

大量资料表明,中缝背核(DR)在痛觉调节中具有重要作用。本实验用电生理学方法研究DR在痛觉调制中的下行性抑制作用,主要观察刺激DR对清醒制动大鼠脊髓背角神经元伤害性放电的影响。其主要结果是:①刺激DR或电针可以抑制脊髓背角神经元的伤害性反应,吗啡可加强这种抑制效应;②损毁中缝大核(NRM)、纳洛酮、麦角酰二乙胺(LSD)、赛庚啶及对氯苯丙氨酸(PCPA)均能部分阻断DR对脊髓背角神经元伤害性反应的抑制,实验结果表明:刺激DR抑制脊髓背角神经元的伤害性反应,部分是通过NRM间接控制背角神经元的伤害性传入;还有一部分是不通过NRM,可能是DR直接对脊髓背角伤害性信息的调制。在这种下行性抑制通路中有5-HT和阿片样物质的参与。