CT引导下立体定向射频热凝三叉神经半月节对原发性三叉神经痛的疗效分析

目的：分析CT引导下立体定向射频热凝三叉神经半月节对原发性三叉神经痛的疗效,探讨其临床适用性。方法：选择从2011年5月至2012年12月于我院住院治疗原发性三叉神经痛的58例患者,在三维CT引导下采用通过BrainLAB手术计划系统经前入路卵圆孔穿刺三叉神经半月神经节,术中根据疼痛分布范围射频热凝三叉神经半月节。观察并比较治疗前后的VAS评分,临床疗效,术中和术后不良反应情况。结果：58例患者的穿刺手术均成功,术后1d、3d、6d的VAS评分均较治疗前显著降低（P〈0．01）;1周后58例患者中,有53例患者疼痛完全消失,l例患者偶然出现疼痛,但无需服用药物处理,共显效54例;4例患者疼痛有所减轻或疼痛发作频率降低,但仍需服用药物,或服用药物剂量较治疗前明显减少;疼痛无改善或者非用药不能缓解的持续痛仅1例。总有效例数为57例,总有效率达98．26％。术中发生不良反应6例,在术后均有所缓解。术后发生各种并发症共15例,均未明显影响手术效果。结论：CT引导可以较为准确的进入穿刺部位,使立体定向射频热凝三叉神经半月节手术更加顺利,达到治疗原发性三叉神经痛的理想效果,适合临床长期推广应用。     

BK(Ca) channel agonist NS1619 and Kv channel antagonist 4-AP on the facial mechanical pain threshold in a rat model of chronic constriction injury of the infraorbital nerve

Trigeminal neuralgia is a paroxysmal disorder with severely disabling facial pain and thus continues to be a real therapeutic challenge. At present there are few effective drugs for treatment of this pain. The present study was aimed to explore the involvement of BK(Ca) channels and Kv channels in the mechanical allodynia in a rat model of trigeminal neuropathic pain. Here the effectiveness of drug target injection at the trigeminal ganglion through the infraorbital foramen was first evaluated by immunofluorescence and animal behavior test. Trigeminal neuropathic pain model was established by chronic constriction injury of the infraorbital nerve (ION-CCI) in rats. BK(Ca) channel agonist and Kv channel antagonist were administered into the trigeminal ganglion in ION-CCI rats and sham rats by the above target injection method, and the facial mechanical pain threshold was measured. The results showed that the drug could accurately reach the trigeminal ganglion by target injection which was more effective than that by the normal injection around infraorbital foramen. Rats suffered significant mechanical allodynia in the whisker pad of the operated side from 6 d to 42 d after ION-CCI. BK(Ca) channel agonist NS1619 significantly and dose-dependently attenuated the facial mechanical allodynia and increased the facial mechanical pain threshold in ION-CCI rats 15 d after operation. Kv antagonist 4-AP was able to reduce the threshold in ION-CCI rats when facial mechanical threshold was partly recovered and relatively stable on the 35th day after operation. These results suggest that BK(Ca) channel agonist NS1619 and Kv channel antagonist 4-AP can significantly affect the rats' facial mechanical pain threshold after ION-CCI. Activation of BK(Ca) channels may be related to the depression of the primary afferent neurons in trigeminal neuropathic pain pathways. Activation of Kv channels may exert a tonic inhibition on the trigeminal neuropathic pain.     

Electrical stimulation of the trigeminal tract in chronic, intractable facial neuralgia

In this paper the treatment of patients with chronic, intractable trigeminal neuralgia by invasive electrical stimulation of the Gasserion ganglion is reviewed. Two different surgical techniques are employed in this treatment. Most frequently, a method similar to the traditional technique for percutaneous glycerol and radiofrequency trigeminal rhizolysis is used: a small percutaneous stimulation electrode is advanced under fluoroscopic control through a thin needle via the foramen ovale to the Gasserian cistern. Some neurosurgeons use an open surgical technique by which the Gasserian ganglion is approached subtemporally and extradurally, and the bipolar pad electrode is sutured to the dura. When percutaneous test stimulation is successful (at least 50% pain relief) the electrode is internalized and connected to a subcutaneous pulse generator or RF-receiver. Data from 8 clinical studies, including 267 patients have been reviewed. Of all 233 patients with medication-resistant atypical trigeminal neuralgia 48% had at least 50% long term pain relief. The result of test stimulation is a good predictor of the long term effect, because 83% of all patients with successful test stimulation had at least 50% long term relief, and 70% had at least 75% long term relief. Patients generally preferred this invasive method over TENS. The success rate in patients with postherpetic trigeminal neuralgia was very low (less than 10%). It is suggested that the likelihood of pain relief by electrical stimulation is inversely related to the degree of sensory loss. It is concluded that invasive stimulation of the Gasserian ganglion is a promising treatment modality for patients with chronic, intractable, atypical trigeminal neuralgia.     

Reorganization of the Peripheral Projections of the Trigeminal Ganglion Following Neonatal Transection of the Infraorbital Nerve

Two different anatomical techniques were used to obtain evidence that transection of the infraorbital (IO) nerve on the day of birth would result in reorganization of the peripheral projections of the trigeminal nerve. In 14 of 19 neonatally nerve-damaged adult rats, injection of horseradish peroxidase (HRP) directly into the IO nerve, proximal to the point of the neonatal transection, resulted in labeled cells in the ophthalmic-maxillary portion of the ganglion and labeled fibers in mandibular sensory nerves. In an additional 28 neonatally nerve-damaged adult rats, double-labeling techniques were employed to document the reorganization suggested by the HRP tracing experiments. In these experiments, one fluorescent tracer, diamidino yellow (DY), was injected directly into the regenerate IO nerve, proximal to the point of the neonatal transection; a second tracer, true blue (TB), was deposited into peripheral ophthalmic and/ or mandibular fields. These combinations of injections invariably resulted in the demonstration of a small number (46-401) of double-labeled cells that were located in the ophthalmic-maxillary part of the ganglion. Identical combinations of injections in normal adult rats and the intact sides of nerve-damaged animals never produced more than 6 double-labeled cells per ganglion.

In two additional series of experiments, sequential double-labeling techniques were employed to demonstrate that the multiply projecting ganglion cells probably arose in at least two ways: (1) development of non-IO projections by ganglion cells that contributed axons to the IO nerve at the time of the lesion; (2) elaboration of IO axon branches by primary afferent neurons that had non-IO projections at the time of the lesion. A final two-stage double-labeling experiment demonstrated that approximately 75% of the ganglion cells that projected to the whisker pad at birth, and survived transection of the IO nerve on the first postnatal day, regenerated axons into this trigeminal branch.     

Trigeminal Projections to Contralateral Dorsal Horn Originate in Midline Hairy Skin

The present study tested the hypothesis that the trigeminal (V) primary afferent projection to the contralateral dorsal horn originates in midline hairy skin. A prior study (Jacquin et al., 1990) showed that this crossed projection is heaviest to ophthalmic regions of medullary and cervical dorsal horns, and that it does not arise from V ganglion cells that innervate cornea, nasal mucosa, or cerebral dura mater. Here, retrograde double-labeling methods were used to show that many ophthalmic ganglion cells that innervate midline hairy skin via the supraorbital nerve project to the contralateral medullary and upper cervical dorsal horns. Diamidino yellow injections into the right dorsal horn labeled an average of 104 cells in the left V ganglion. Of these contralaterally projecting ganglion cells, an average of 45% were also labeled by horseradish peroxidase (HRP) injections into the left supraorbital nerve, and 25% were also labeled by HRP injections into the midline opthalmic hairy skin. However, only 2% were labeled by HRP injections restricted to left supraorbital vibrissae follicle nerves. Almost all of the double-labeled cells were located in the dorsal one-half of the V ganglion, and they did not differ in size from single-labeled cells.

On the basis of these and prior data, we conclude that a high percentage of contralaterally projecting V ganglion cells originate in midline hairy skin. It is also likely that the contralaterally projecting V ganglion cells serve a low-threshold mechanoreceptive function, given the relatively large ganglion cells and axons giving rise to this pathway and their central terminations in dorsal horn laminae III-V.     

Trigeminal projections to contralateral dorsal horn originate in midline hairy skin

The present study tested the hypothesis that the trigeminal (V) primary afferent projection to the contralateral dorsal horn originates in midline hairy skin. A prior study (Jacquin et al., 1990) showed that this crossed projection is heaviest to ophthalmic regions of medullary and cervical dorsal horns, and that it does not arise from V ganglion cells that innervate cornea, nasal mucosa, or cerebral dura mater. Here, retrograde double-labeling methods were used to show that many ophthalmic ganglion cells that innervate midline hairy skin via the supraorbital nerve project to the contralateral medullary and upper cervical dorsal horns. Diamidino yellow injections into the right dorsal horn labeled an average of 104 cells in the left V ganglion. Of these contralaterally projecting ganglion cells, an average of 45% were also labeled by horseradish peroxidase (HRP) injections into the left supraorbital nerve, and 25% were also labeled by HRP injections into the midline opthalmic hairy skin. However, only 2% were labeled by HRP injections restricted to left supraorbital vibrissae follicle nerves. Almost all of the double-labeled cells were located in the dorsal one-half of the V ganglion, and they did not differ in size from single-labeled cells. On the basis of these and prior data, we conclude that a high percentage of contralaterally projecting V ganglion cells originate in midline hairy skin. It is also likely that the contralaterally projecting V ganglion cells serve a low-threshold mechanoreceptive function, given the relatively large ganglion cells and axons giving rise to this pathway and their central terminations in dorsal horn laminae III-V.     

Substance P-like immunoreactivity in the trigeminal ganglion. A fluorescence, light and electron microscope study

The trigeminal ganglion of rat and guinea pig was studied for the presence of immunoreactive substance-P using fluorescence, light and electronmicroscopy. In untreated animals substance P containing cells, with a diameter of 15 to 50 micron, were distributed throughout the ganglion and comprised 10-30% of all ganglion cells. Colchicine, injected intraventricularly to inhibit intra-axonal transport, had no effect on the number of substance P cells; but when the drug was injected directly into the posterior root of the ganglion, the proportion of these cells increased to as much as 50%. In the electron microscope, immunoreactive substance-P was confined to ganglion cells classified as B type according to the arrangement of subcellular organelles, and to unmyelinated nerve fibers. Subcellularly the immunoreactivity appeared in cytoplasmic vesicles, as well as dispersed in the nerve fibers and the perikarya of neurons. The great number of substance P immunoreactive ganglion cells suggests that they do not comprise a well defined subpopulation of the B-cells. However, the immunoreactivity was restricted to a distinct ultrastructural type of neurons with unmyelinated nerve fibers, suggesting that they also may share some distinct functions.     

Localization and somatotopy of sensory cells innervating the extraocular muscles of lamb, pig and cat. Histochemical and electrophysiological investigation

The localization of sensory cells innervating the extraocular muscles (EOMs) was studied in the lamb, pig and cat in which horseradish peroxidase (HRP) was injected into each EOM. Electrophysiological techniques were also used to search for EOM stretch sensitive units in the semilunar ganglion. In lamb and pig labeling was observed in the semilunar ganglion only, while in cat labeled neurons were present in both the semilunar ganglion and mesencephalic trigeminal nucleus. In the semilunar ganglion of all these species a clear somatotopic organization of EOM afferents was observed. The histochemical somatotopic pattern of EOM afferents in the semilunar ganglion of lamb and pig was substantially in agreement with the electrophysiological arrangement. The responses recorded to EOM stretch in the semilunar ganglion of the pig were characterized by a low threshold and a slow adaptation as previously found in the lamb; on the contrary, in the semilunar ganglion of the cat only a few units were found, which showed high stretch threshold and quick adaptation.     

Corpuscular bodies in the palate of the rat. 2. Innervation and central projection.

The source of innervation of the corpuscular bodies in the palate and the central projections of the afferent fibres of the entire palate was studied in rats by transganglionic transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) and with substance P (SP) immunohistochemistry. WGA-HRP injected into the incisal papilla was taken up by the nerve fibres that terminated in the corpuscles. Retrogradely labelled neurons were observed in the trigeminal ganglion as well as anterogradely labelled terminals in the dorsolateral part of the spinal trigeminal nucleus and in the lateral part of the nucleus of the solitary tract. No labelling could be found in the geniculate ganglion, the facial nerve and the hypoglossal nucleus. Following WGA-HRP injection in the intermolar area and in the soft palate, labelling was only restricted to the trigeminal ganglion. The lamina propria of the entire palate and the corpuscle-enriched area of the incisal papilla and the soft palate were richly innervated by SP-containing fibres. Numerous SP-containing fibres were also observed in the nerve plexus at the base of the corpuscle. In addition, SP-positive neurons were identified in the trigeminal ganglion and SP-labelled terminals in the sensory trigeminal nuclear complex and in the solitary tract nucleus. On the basis of our morphological observations we conclude that the palatal corpuscular bodies are involved in taste perception which is of trigeminal origin.     

蛇类红外线感受系统:一种可能的外气功研究实验动物模型

许多蛇类,例如响尾蛇属,洞蛇属,饭匙倩蛇属,竹叶青蛇属和蝮蛇属等在头部具有一对能在黑暗中探测和捕获猎物的凹陷器官。这种凹陷器官对红外射线非常敏感,因此也称为红外线感受器官。凹陷器官在中间部位被一层约为15μm厚的薄膜(红外线感受膜)分隔为外腔和内腔,红外线感受膜由三叉神经节中的特化假单极神经细胞(红外线感受细胞)的外周轴突所支配,红外线感受膜内相邻的游离神经末梢聚合形成约40μm直径的团块,构成了基本的红外线感受野单元。三叉神经节中的红外线感受细胞的中枢轴突投射到同侧延髓中的三叉神经束外侧降核,该神经核团为此类蛇属所特有。从三叉神经束外侧降核二级神经元发出的轴突投射到对侧视顶盖。由于蛇类不具有分化的半球新皮质,因此视顶盖为红外线感受系统的感觉与行为的整合中枢。在三叉神经节,延髓三叉神经束外侧降核及视顶盖均可记录到神经细胞对红外线刺激的反应电位,从而可观察红外线刺激强度与各级红外线感受神经元反应强度的关系。本文简述了蛇类红外线感受系统的形态学和生理学特征及其研究进展,并且探讨了利用蛇类红外线感受系统作为生物体接受外气功研究的实验动物模型的可能性。     

Correlated appearance of ossification and nerve tissue in human fetal jaws.

The factors initiating the onset of desmal jaw formation are not known. The purpose of the present report was to examine the correlation between the appearance of ossification and nerve tissue in human fetal jaws. This was done through elaboration of similarities in occurrence of tissue types at four different sites of initial bone formation in the jaws. Radiological and histochemical methods applied to the jaws of 26 human embryos/fetuses revealed that nerve tissue appeared in the jaws before bone tissue. Early bone formation occurred in close relation to the mandibular nerve, the maxillary nerve, the palatine nerve, and the naso-palatine nerve. It is suggested that the foramina (mental foramen, infraorbital foramen, palatal foramen, and incisive foramen) are the areas of incipient bone formation, and that the sequence in bone formation corresponds to the sequence in the development of nerve fibers from the trigeminal ganglion.     

小鼠眼神经注入Dil后三叉神经节的形态学研究

目的：经眼神经注入DiI研究小鼠三叉神经节的形态学结构。方法：小鼠10只,体重25—30克,雌雄不拘,进行灌注固定后,在外科显微镜下开颅并确认三叉神经节和眼神经,分别于双侧眼神经植入DiI染色晶体。37℃恒温箱放置3个月,待DiI染色晶体扩散后,取出植入DiI染色晶体的眼神经和三叉神经节,再根据神经走向切片,通过荧光显微镜观察DiI染色晶体在三又神经节内的分布。结果：眼神经离三叉神经节约1cm处植入DiI染色晶体后,应用荧光显微镜明视野观察,均可见到高密度标记的眼神经纤维,行向后内,穿经眶上裂入颅。逐步靠近三叉神经节外上方,并进入三叉神经节内,眼神经标记的神经元位于三叉神经节的前内侧。在三叉神经节内可见到DiI标记的神经节细胞及神经纤维。神经纤维平行致密排列,并被神经节细胞神经纤维分隔成群或簇。神经节细胞呈圆形和卵圆形,大小不一,部分节细胞呈蜂窝状排列。亦可见神经元的突起,有的呈螺旋状连于胞体,有的呈线状连于胞体,并可见到双极神经元。结论：小鼠经眼神经注入DiI后,三叉神经节细胞和神经纤维的排列循序跟其他动物基本一致。     

Substance P-like immunoreactivity in the trigeminal ganglion

Summary The trigeminal ganglion of rat and guinea pig was studied for the presence of immunoreactive substance-P using fluorescence, light and electronmicroscopy. In untreated animals substance P containing cells, with a diameter of 15 to 50 m, were distributed throughout the ganglion and comprised 10–30% of all ganglion cells. Colchicine, injected intraventricularily to inhibit intra-axonal transport, had no effect on the number of substance P cells; but when the drug was injected directly into the posterior root of the ganglion, the proprotion of these cells increased to as much as 50%. In the electron microscope, immunoreactive substance-P was confined to ganglion cells classified as B type according to the arrangement of subcellular organelles, and to unmyelinated nerve fibers. Subcellularily the immunoreactivity appeared in cytoplasmic vesicles, as well as dispersed in the nerve fibers and the perikarya of neurons. The great number of substance P immunoreactive ganglion cells suggests that they do not comprise a well defined subpopulation of the B-cells.However, the immunoreactivity was restricted to a distinct ultrastructural type of neurons with unmyelinated nerve fibers, suggesting that they also may share some distinct functions.     

Pudendal and caudal rectal nerve blocks in the horse - An anesthetic procedure for reproductive surgery

The pudendal and caudal rectal nerves in four male and five female adult crossbred horses were anesthetized with a local solution. The injection site was located at the foramen for the caudal gluteal artery and vein in the sacrosciatic ligament. Twenty milliliters of local anesthetic solution were injected via a 15-cm, 18-gauge needle. Quantitative data on anesthesia were determined from these injections. Dye was injected with the anesthetic in four additional horses so that accurate placement of the solution could be determined at postmortem examination. Satisfactory anesthesia of the anus, perineum, and vulva in the mare and of the anus, perineum, glans penis and penile layer of the prepuce in the male was achieved by placement of anesthetic near the foramen for the caudal gluteal vessels in the sacrosciatic ligament. Penile extrusion also occurred.     

Catatonic or hypotonic immobility induced in mice by intracerebroventricular injection of mu or kappa opioid receptor agonists as well as enkephalins or inhibitors of their degradation

The intracerebroventricular injections in mice of the mu receptor agonists morphine and fentanyl induced an immobility state (the animals staying motionless with the head down on a 45° inclined plane) which was apparently hypertonic (catatonia ?) or at least enabled them to remain hanging on a horizontal wire with their forepaws. In similar conditions, injections of the kappa receptor agonists ketocyclazocine and bremazocine induced an immobility state which was hypotonic, in contrast with the preceding one. In a similar way to the mu agonists, Met-enkephalin or Leu-enkephalin injected i.c.v. in association with the inhibitor of enkephalinase thiorphan induced an apparently hypertonic immobility which was easily antagonized by naloxone. The association of thiorphan with bestatin ( an inhibitor of aminopeptidases involved in enkephalins inactivation ) produced similar results. In contrast, the hypotonic immobility induced by the kappa receptor agonists required relatively high doses of naloxone to be antagonized. The opiate antagonist MR 2266 antagonized equipotent doses of all the above mentioned agents with a similar efficacy. From these data it is suggested that enkephalins could induce an apparently tonic immobility by stimulating mu receptors and that endogenous enkephalins could be involved in a tonic mediation modulating the locomotor activity or regulating the muscular tone.     

A transgene containing lacZ is expressed in primary sensory neurons in zebrafish.

In order to screen for developmentally active chromosomal domains during zebrafish embryogenesis, we generated transgenic fish by microinjecting two different lacZ reporter constructs into fertilized eggs. Transgenic fish were screened among the progeny of injected fish (F0) crossed to non-injected fish. Groups of 15 to 20 progeny of each cross were tested for lacZ expression and/or transmission of injected sequences using PCR and Southern hybridizations. Progeny from 2 of 102 fish injected with supercoiled constructs containing Rous sarcoma virus promoter sequences showed apparently spatially regulated beta-galactosidase (beta-Gal) activity. However, we were not able to detect this reporter construct in DNA from fins of F1 fish. Injections of a linear reporter construct containing mouse heat-shock promoter sequences revealed transmission of injected sequences to F1 progeny in about 6% of cases (8 of 129 fish, tested with PCR). We found one lacZ-expressing line that showed a spatially and temporally restricted expression of lacZ and, therefore, features typical characteristics of "enhancer trap" lines. In this line, lacZ expression starts at 16 hours post-fertilization in trigeminal ganglion cells. At about 24 hours lacZ expression can be detected in trigeminal ganglion neurons and Rohon-Beard neurons, indicating that the development of these two cell types shows common features. The reporter gene has integrated as a single copy. The founder fish was mosaic: 19% of its offspring (3 of 16 tested animals) carried the reporter construct in their fins; about 51% (13 of 27 tested animals) of the progeny of F1 fish were beta-Gal positive indicating full hemizygosity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocannabinoids, their effect on GABA uptake in globus pallidus and relevance to Parkinson's disease

Histochemical, immunocytochemical and radioassay study was performed to detect the occurrence of NOS-immunoreactive primary trigeminal sensory somata in the trigeminal ganglion, including their fiber components. Spinal trigeminal tract and sensory trigeminal nuclei were studied using the same methods. It was found that more than 30% of all somata in the trigeminal ganglion are NOS immunoreactive. Corresponding fibers were detected in the spinal trigeminal tract. NOS immunoreactive fibers of three different categories could be followed to terminate in the sensory trigeminal nuclei. Data presented here confirm that trigeminal sensory system is richly endowed with NOS and that NO is used to communicate between the first and second-order trigeminal sensory neurons.
Acknowledgements:   Supported by VEGA Grant no. 2/3217/23PS9, STAA Grant no. 51-013002 and by NIH grants NS 32794 and NS 40386 to M.M.     

LHRH neuronal migration: heterotypic transplantation analysis of guidance cues

During embryonic development, the olfactory placode (OP) differentiates into the olfactory epithelium (OE). Luteinizing hormone-releasing hormone (LHRH) neurons migrate out of the OE in close association with the olfactory nerve (ON) to the telencephalon. LHRH neuronal migration and ON extension to the telencephalon may be independent events which are correlated but do not represent a causal relationship. However, we hypothesize that LHRH neurons are dependent on ON axons to migrate to the brain. To test this hypothesis, we ablated the right trigeminal placode and replaced it with an OP from another chick embryo. After several days' additional incubation, the embryos were fixed, sectioned, and immunostained with antibodies against LHRH or N-CAM. The ectopic OPs were well integrated into the host and developed into relatively normal appearing OEs. The ONs extended from the OE to several different sites: the lateral rectus of the eye, the ciliary ganglion, and the trigeminal ganglion. In all cases, LHRH neurons were found in the OE and ON, regardless of where the ON terminated. When the ON extended to the trigeminal ganglion, LHRH neurons could clearly be seen entering the metencephalon. Our results support the idea that LHRH neurons are dependent on the ON for guidance as they appear to follow the nerve even when it extends away from the brain. The cues which direct the ON and LHRH neurons to the telencephalon do not appear to be unique to this brain region.     

NO participate in the communication between the first‐ and second‐order neurons in the trigeminal sensory tract in the dog

Histochemical, immunocytochemical and radioassay study was performed to detect the occurrence of NOS‐immunoreactive primary trigeminal sensory somata in the trigeminal ganglion, including their fiber components. Spinal trigeminal tract and sensory trigeminal nuclei were studied using the same methods. It was found that more than 30% of all somata in the trigeminal ganglion are NOS immunoreactive. Corresponding fibers were detected in the spinal trigeminal tract. NOS immunoreactive fibers of three different categories could be followed to terminate in the sensory trigeminal nuclei. Data presented here confirm that trigeminal sensory system is richly endowed with NOS and that NO is used to communicate between the first and second‐order trigeminal sensory neurons. Acknowledgements: Supported by VEGA Grant no. 2/3217/23PS9, STAA Grant no. 51‐013002 and by NIH grants NS 32794 and NS 40386 to M.M.