SCN2B in the Rat Trigeminal Ganglion and Trigeminal Sensory Nuclei

The beta-2 subunit of the mammalian brain voltage-gated sodium channel (SCN2B) was examined in the rat trigeminal ganglion (TG) and trigeminal sensory nuclei. In the TG, 42.6 % of sensory neurons were immunoreactive (IR) for SCN2B. These neurons had various cell body sizes. In facial skins and oral mucosae, corpuscular nerve endings contained SCN2B-immunoreactivity. SCN2B-IR nerve fibers formed nerve plexuses beneath taste buds in the tongue and incisive papilla. However, SCN2B-IR free nerve endings were rare in cutaneous and mucosal epithelia. Tooth pulps, muscle spindles and major salivary glands were also innervated by SCN2B-IR nerve fibers. A double immunofluorescence method revealed that about 40 % of SCN2B-IR neurons exhibited calcitonin gene-related peptide (CGRP)-immunoreactivity. However, distributions of SCN2B- and CGRP-IR nerve fibers were mostly different in facial, oral and cranial structures. By retrograde tracing method, 60.4 and 85.3 % of TG neurons innervating the facial skin and tooth pulp, respectively, showed SCN2B-immunoreactivity. CGRP-immunoreactivity was co-localized by about 40 % of SCN2B-IR cutaneous and tooth pulp TG neurons. In trigeminal sensory nuclei of the brainstem, SCN2B-IR neuronal cell bodies were common in deep laminae of the subnucleus caudalis, and the subnuclei interpolaris and oralis. In the mesencephalic trigeminal tract nucleus, primary sensory neurons also exhibited SCN2B-immunoreactivity. In other regions of trigeminal sensory nuclei, SCN2B-IR cells were very infrequent. SCN2B-IR neuropil was detected in deep laminae of the subnucleus caudalis as well as in the subnuclei interpolaris, oralis and principalis. These findings suggest that SCN2B is expressed by various types of sensory neurons in the TG. There appears to be SCN2B-containing pathway in the TG and trigeminal sensory nuclei.     

Mapping of the trigeminal sensory complex of the cat. Characterization of its neurons by stimulations of peripheral field, dental pulp afferents and thalamic projections.

From a new systematic investigation of the 4 divisions of the trigeminal sensory complex, the following points are emphasized: 1. The subnucleus oralis receives a large representation from the oral cavity, a region also represented in the three other divisions of the trigeminal sensory complex. 2. Units responding to noxious mechanical stimulation have been found in two different loci: the subnucleus caudalis for the whole trigeminal area, and the subnucleus oralis for the oral cavity. 3. The dental pulp projects to the four divisions of the trigeminal sensory complex, but the heaviest projection is found in its rostral part (the main nucleus and subnucleus oralis). 4. Three distinct types of responses were found following dental pulp stimulation: primary, non primary and responses strongly enhanced by an increase in stimulus parameters.     

Neurobiology of trigeminal pain

The brainstem trigeminal complex integrates somatosensory inputs from orofacial areas and meninges. Recent studies have shown the existence of a double representation of pain within the brainstem, at the level of both caudalis and oralis subnuclei. Noxious messages are mainly conveyed by C-fibers that activate the subnucleus caudalis neurons. These neurons in turn activate the subnucleus oralis whose neurons share similar features with the deep spinal dorsal horn neurons. In contrast with the nearness of the laminar organization of the dorsal horn, the vertical organization of the trigeminal complex offers an easier access for the study of segmental mechanisms of nociceptive processing. This model allowed us to show the existence of subtle NMDA-related mechanisms of segmental nocious processing. The trigeminal complex conveys nociceptive messages to several brainstem and thalamic relays that activate a number of cortical areas responsible for pain sensations and reactions. Cortical processing is sustained by reciprocal interactions with thalamic areas and also by a direct modulation of their pre-thalamic relays. The dysfunction of these multiple modulatory mechanisms probably plays a key role in the pathophysiology of chronic trigeminal pain.     

SPARCL1-containing neurons in the human brainstem and sensory ganglion

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a member of the osteonectin family of proteins. In this study, immunohistochemistry for SPARCL1 was performed to obtain its distribution in the human brainstem, cervical spinal cord, and sensory ganglion. SPARCL1-immunoreactivity was detected in neuronal cell bodies including perikarya and proximal dendrites, and the neuropil. The motor nuclei of the IIIrd, Vth, VIth, VIIth, IXth, Xth, XIth, and XIIth cranial nerves and spinal nerves contained many SPARCL1-immunoreactive (-IR) neurons with medium-sized to large cell bodies. Small and medium-sized SPARCL1-IR neurons were distributed in sensory nuclei of the Vth, VIIth, VIIIth, IXth, and Xth cranial nerves. In the medulla oblongata, the dorsal column nuclei also had small to medium-sized SPARCL1-IR neurons. In addition, SPARCL1-IR neurons were detected in the nucleus of the trapezoid body and pontine nucleus within the pons and the arcuate nucleus in the medulla oblongata. In the cervical spinal cord, the ventral horn contained some SPARCL1-IR neurons with large cell bodies. These findings suggest that SPARCL1-containing neurons function to relay and regulate motor and sensory signals in the human brainstem. In the dorsal root (DRG) and trigeminal ganglia (TG), primary sensory neurons contained SPARCL1-immunoreactivity. The proportion of SPARCL1-IR neurons in the TG (mean?±?SD, 39.9?±?2.4%) was higher than in the DRG (30.6?±?2.1%). SPARCL1-IR neurons were mostly medium-sized to large (mean?±?SD, 1494.5?±?708.3?μm²; range, 320.4–4353.4?μm²) in the DRG, whereas such neurons were of various cell body sizes in the TG (mean?±?SD, 1291.2?±?532.8?μm²; range, 209.3–4326.4?μm²). There appears to be a SPARCL1-containing sensory pathway in the ganglion and brainstem of the spinal and trigeminal nervous systems.     

Intersubnuclear connections within the rat trigeminal brainstem complex

Prior intracellular recording and labeling experiments have documented local-circuit and projection neurons in the spinal trigeminal (V) nucleus with axons that arborize in more rostral and caudal spinal trigeminal subnuclei and nucleus principalis. Anterograde tracing studies were therefore carried out to assess the origin, extent, distribution, and morphology of such intersubnuclear axons in the rat trigeminal brainstem nuclear complex (TBNC). Phaseolus vulgaris leucoagglutinin (PHA-L) was used as the anterograde marker because of its high sensitivity and the morphological detail provided. Injections restricted to TBNC subnucleus caudalis resulted in dense terminal labeling in each of the more rostral ipsilateral subnuclei. Subnucleus interpolaris projected ipsilaterally and heavily to magnocellular portions of subnucleus caudalis, as well as subnucleus oralis and nucleus principalis. Nucleus principalis, on the other hand, had only a sparse projection to each of the caudal ipsilateral subnuclei. Intersubnuclear axons most frequently traveled in the deep bundles within the TBNC, the V spinal tract, and the reticular formation. They gave rise to a number of circumscribed, highly branched arbors with many boutons of the terminal and en passant types. Retrograde single- or multiple-labeling experiments assessed the cells giving rise to TBNC intersubnuclear collaterals. Horseradish peroxidase (HRP) and/or fluorescent tracer injections into the thalamus, colliculus, cerebellum, nucleus principalis, and/or subnucleus caudalis revealed large numbers of neurons in subnuclei caudalis, interpolaris, and oralis projecting to the region of nucleus principalis. Cells projecting to more caudal spinal trigeminal regions were most numerous in subnuclei interpolaris and oralis. Some cells in lamina V of subnucleus caudalis and in subnuclei interpolaris and oralis projected to thalamus and/or colliculus, as well as other TBNC subnuclei. Such collateral projections were rare in nucleus principalis and more superficial laminae of subnucleus caudalis. TBNC cells labeled by cerebellar injections were not double-labeled by tracer injections into the thalamus, colliculus, or TBNC. These findings lend generality to currently available data obtained with intracellular recording and HRP labeling methods, and suggest that most intersubnuclear axons originate in TBNC local-circuit neurons, though some originate in cells that project to midbrain and/or diencephalon.     

Intersubnuclear Connections within the Rat Trigeminal Brainstem Complex

Prior intracellular recording and labeling experiments have documented local-circuit and projection neurons in the spinal trigeminal (V) nucleus with axons that arborize in more rostral and caudal spinal trigeminal subnuclei and nucleus principalis. Anterograde tracing studies were therefore carried out to assess the origin, extent, distribution, and morphology of such intersubnuclear axons in the rat trigeminal brainstem nuclear complex (TBNC). Phaseolus vulgaris leucoagglutinin (PHA-L) was used as the anterograde marker because of its high sensitivity and the morphological detail provided. Injections restricted to TBNC subnucleus caudalis resulted in dense terminal labeling in each of the more rostral ipsilateral subnuclei. Subnucleus interpolaris projected ipsilaterally and heavily to magnocellular portions of subnucleus caudalis, as well as subnucleus oralis and nucleus principalis. Nucleus principalis, on the other hand, had only a sparse projection to each of the caudal ipsilateral subnuclei. Intersubnuclear axons most frequently traveled in the deep bundles within the TBNC, the V spinal tract, and the reticular formation. They gave rise to a number of circumscribed, highly branched arbors with many boutons of the terminal and en passant types.

Retrograde single- or multiple-labeling experiments assessed the cells giving rise to TBNC intersubnuclear collaterals. Horseradish peroxidase (HRP) and/or fluorescent tracer injections into the thalamus, colliculus, cerebellum, nucleus principalis, and/or subnucleus caudalis revealed large numbers of neurons in subnuclei caudalis, interpolaris, and oralis projecting to the region of nucleus principalis. Cells projecting to more caudal spinal trigeminal regions were most numerous in subnuclei interpolaris and oralis. Some cells in lamina V of subnucleus caudalis and in subnuclei interpolaris and oralis projected to thalamus and/or colliculus, as well as other TBNC subnuclei. Such collateral projections were rare in nucleus principalis and more superficial laminae of subnucleus caudalis. TBNC cells labeled by cerebellar injections were not double-labeled by tracer injections into the thalamus, colliculus, or TBNC.

These findings lend generality to currently available data obtained with intracellular recording and HRP labeling methods, and suggest that most intersubnuclear axons originate in TBNC local-circuit neurons, though some originate in cells that project to midbrain and/or diencephalon.     

Gamma-aminobutyric acid-immunoreactive neurons in the rat trigeminal nuclei

The distribution of GABAergic neurons in the rat trigeminal nuclei was studied using a highly specific monoclonal antibody (mAb3A12) to gamma-aminobutyric acid (GABA). Immunopositive cells were relatively abundant in the marginal and gelatinosa beds of the caudal part of the trigeminal spinal tract nucleus, and in the dorsomedial areas of the oral subnucleus and the principal nucleus. A high density of GABA-immunoreactive somata was also found in the rostral part of the oral subnucleus and in the adjacent parvicellular reticular formation as well as in the supratrigeminal and intertrigeminal regions. Thus, the distribution of the GABAergic cells showed a relatively high density in areas related to the convergence of sensory stimuli, and in zones that contain interneurons inhibiting masticatory motorneurons. The results suggest, therefore, that GABA might play an important role both in discriminative sensory processing and in reflex modulation of the orofacial region.Abbreviations RF reticular formation - FRp parvicellular reticular formation - Vc trigeminal nucleus of the spinal tract, subnucleus caudalis - Vmes mesencephalic nucleus - Vmo trigeminal motor nucleus - Vo trigeminal nucleus of the spinal tract, subnucleus oralis - Vp principal trigeminal nucleus - Vsp spinal trigeminal nucleus - Vsup supratrigeminal nucleus     

Organization,development, and effects of infraorbital nerve transection on galanin binding sites in the trigeminal brainstem complex

Previous experiments from this laboratory have indicated that transection of the infraorbital nerve (ION, the trigeminal \[V] branch that supplies the mystacial vibrissae follicles) at birth and in adulthood has markedly different effects on galanin immunoreactivity in the V brainstem complex. Adult nerve transection increases galanin immunoreactivity in the superficial layers of V subnucleus caudalis (SpC) only, while neonatal nerve transection results in increased galanin expression in vibrissae-related primary afferents throughout the V brainstem complex. The present study describes the distribution of binding sites for this peptide in the mature and developing V ganglion and brainstem complex and determines the effects of neonatal and adult ION damage and the associated changes in galanin levels upon their distribution and density. Galanin binding sites are densely distributed in all V brainstem subnuclei and are particularly dense in V subnucleus interpolaris and the superficial layers of SpC. They are present at birth (P-0) and their distribution is similar to that in adult animals. Transection of the ION in adulthood and examination of brainstem 7 days later indicated marked reductions in the density of galanin binding sites in the V brainstem complex. With the exception of the superficial laminae of SpC, the same reduction in density remained apparent in rats that survived 45 days after nerve cuts. Transection of the ION on P-0 resulted in no change in the density of galanin binding sites in the brainstem after either 7 or 60 days survival. These results indicate that densely distributed galanin binding sites are present in the V brainstem complex of both neonatal and adult rats, that they are located in regions not innervated by galanin-positive axons, and that their density is not significantly influenced by large lesion-induced changes in the primary afferent content of their natural ligand.     

Neuropathology in sensory,but not motor,brainstem nuclei of the rat whisker circuit after diffuse brain injury

Neurological dysfunction after traumatic brain injury (TBI) is associated with pathology in cortical, subcortical, and brainstem nuclei. Our laboratory has reported neuropathology and microglial activation in the somatosensory barrel cortex (S1BF) and ventral posterior medial thalamus (VPM) after diffuse TBI in the rat, which correlated with post-injury whisker sensory sensitivity. The present study extends our previous work by evaluating pathology in whisking-associated sensory and motor brainstem nuclei. Brains from adult, male rats were recovered over 1 month after midline fluid percussion or sham injury. The principal trigeminal nucleus (PrV, sensory nucleus) and facial nucleus (VIIN, motor nucleus) were examined for neuropathology (silver histochemistry) and microglial activation (Iba1). Significant neuropathology in PrV was evident at 2 and 7 days post-injury compared to sham. Iba1-labeled microglia showed swollen somata and thickened processes over 1 month post-injury. In contrast, the VIIN showed non-significant neuropathology and reduced labeling of activated Iba1 microglia over 1 month post-injury. Together with our previous data, neuropathology and neuroinflammation in the whisker somatosensory pathway may contribute to post-injury sensory sensitivity more than the motor pathway. Whether these findings are direct results of the mechanical injury or consequences of progressive degeneration remains to be determined.     

Chemoanatomical separation of vibrissal trigeminal primary afferents in the rat: a special central representation of supraorbital vibrissae

A choleratoxin B subunit transganglionic labelling technique and NPY immunohistochemistry were applied in the rat to achieve the chemoanatomical separation of myelinated vibrissal primary afferents, previously considered to be morphologically indistinguishable. Further, a special central representation pattern of supraorbital vibrissae was observed in the trigeminal brainstem nuclear complex: (1) Choleratoxin-labelled supraorbital vibrissal primary afferents terminated densely in their appropriate barrelettes in the trigeminal principal sensory nucleus, in the spinal oral subnucleus, in the caudal part of the spinal interpolar subnucleus, and in lamina IV of the caudal part of the spinal caudal subnucleus. (2) A second population of choleratoxin-labelled vibrissal afferents was also observed, terminating only in lamina III of the caudal subnucleus. (3) After peripheral nerve transection, NPY-immunoreactive supraorbital vibrissal primary afferent fibres appeared in their appropriate barrelettes in the principal sensory nucleus and the caudal part of the interpolar subnucleus, while in the caudal part of the caudal subnucleus NPY-immunoreactive vibrissal primary afferent terminals were found exclusively in the inner part of lamina II, extending over the outer part of lamina III. NPY-immunoreactive supraorbital vibrissal primary afferents were never found in the oral subnucleus. In contrast with the rules of the central representation of the mystacial (infraorbital) vibrissae, the multiple representation of the supraorbital vibrissae in the caudal subnucleus and the dense, barrelette-like terminal arborization of the choleratoxin-labelled supraorbital vibrissal primary afferents in the oral subnucleus apparently indicate an enhanced role of supraorbital vibrissae in reflexes that protect the eyes and the head from damage.     

Nitric oxide-induced increase of excitatory amino acid levels in the trigeminal nucleus caudalis of the rat with tactile hypersensitivity evoked by the loose-ligation of the inferior alveolar nerves

To investigate whether or not N-methyl-D-aspartate (NMDA)/nitric oxide (NO) pathway in the trigeminal system is involved in the development and/or maintenance of such pathological pain states as the hyperalgesia and allodynia observed after dental surgery, we examined the alteration patterns of excitatory amino acid (EAA) level in the superficial layer of subnucleus caudalis of the brain-stem trigeminal sensory nuclear complex (SpVc-I,II) by in vivo microdialysis. A very high EAA release response was observed immediately after the start of the perfusion in ligated animals compared with sham-operated rats. The EAA level evoked by application of the 40-V tooth pulp-stimulation or 1% capsaicin cream was significantly higher in the ligated animals than those in the sham-operated animals. This increase of EAA level induced by capsaicin cream was inhibited by adding carboxy-PTIO (100 microM) to the perfusate. The applications of SNAP (2 mM) into the perfusate enhanced the level of EAAs in ligated animals and sham-operated animals. However, SNAP-evoked EAA levels in ligated animals were not significantly different compared with those of sham-operated animals. These results suggest that alterations in the stimulus-evoked raised EAA levels that occur in the site of the first synaptic relay of the dental pain pathway and which are expressed via endogenous NO, and which play an important role in development and/or maintenance of pathological pain states following dental peripheral nerve injury.     

Involvement of ERK Phosphorylation of Trigeminal Spinal Subnucleus Caudalis Neurons in Thermal Hypersensitivity in Rats with Infraorbital Nerve Injury

To evaluate the involvement of the mitogen-activated protein kinase (MAPK) cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK) in trigeminal spinal subnucleus caudalis (Vc) neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction nerve injury of the infraorbital nerve (ION-CCI). The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR) cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal nerve injury.     

Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. I. Anatomical investigations.

The present research shows that sensory ganglion cells are located within the oculomotor nerve of monkeys and man. Furthermore, afferent fibers have been found in the IIIrd nerve of all the animals examined (lamb, pig, cat, dog and monkey). These fibers have their perikarya prevalently in the semilunar ganglion. Their pathway could be studied after section of either the trigeminal ophthalmic branch or of the intracranial portion of the IIIrd nerve. Following these operations, degenerating fibers were found entering the brain stem through the oculomotor nerve. In the brain stem, they were traced through the pons and the medulla and were seen to end in the spinal cord, within the subnucleus gelatinosus of the nucleus caudalis trigemini. Their degenerating endings found in the neuropil of the SG Rolandi, represented peripheral axonal endings of the glomeruli, rather than central axonal endings, as was the case after trigeminal rhizotomy. On the basis of these different degenerating patterns, the conclusion can be reached that the perikarya of the afferent fibers located in the semilunar ganglion represent, in reality, a ganglion of the IIIrd nerve.     

Lack of quinine-evoked activity in rat trigeminal subnucleus caudalis

Conflicting reports exist regarding the ability of quinine to activate neurons in the trigeminal system. We used the complementary approaches of single-unit electrophysiology and c-fos immunohistochemistry to investigate whether quinine (100 mM) activates chemonociceptive cells in the brainstem trigeminal subnucleus caudalis (Vc). In electrophysiological experiments, 38 units responded to noxious mechanical, thermal and chemical (200 mM pentanoic acid) stimuli applied to the tongue with an increase in firing rate; none responded to lingual quinine whether the quinine was presented before or after application of pentanoic acid. In the c-fos immunohistochemical experiment, both quinine and water elicited equivalent levels of fos-like immunoreactivity (FLI) in dorsomedial Vc that were significantly lower than the level of FLI evoked by pentanoic acid. These data collectively indicate that quinine does not elicit activity in chemonociceptive Vc neurons.     

与咬肌运动神经元直接联系的运动前神经元在脑干的分布

目的为了定位向咬肌运动神经元投射的最后一级运动前神经元在脑干内的分布。方法注射麦芽凝集素结合的辣根过氧化物酶(WGA-HRP)至咬肌神经逆行跨突触追踪,然后通过免疫组织化学方法显示了该类神经元。结果这类神经元分布在双侧三叉上核(Vsup)、三叉神经感觉主核背侧部(Vpdm)、小细胞网状结构(PCR)和三叉神经脊束核吻侧亚核背侧部(Vodm),以及对侧三叉神经运动核(Vmo)。数量上,Vsup,特别是注射侧Vsup中,标记的神经元数量最多;其他核团内,双侧标记的神经元的数量无明显差别。结论一侧咬肌运动神经元直接接受脑干双侧多个区域调控。     

大鼠延髓网状背侧亚核内5-羟色胺能、P物质样和脑啡肽样阳性终末的中枢起源

研究用荧光金（ＦＧ）逆行追踪与免疫荧光组化染色相结合的双标技术对大鼠脑干向延髓网状背侧亚核（ＳＲＤ）的５┐羟色胺（５┐ＨＴ）能、Ｐ物质（ＳＰ）能和亮氨酸┐脑啡肽（Ｌ┐ＥＮＫ）能投射进行了观察。将ＦＧ注入ＳＲＤ后,ＦＧ逆标神经元主要见于中脑导水管周围灰质、脑干中缝核簇（中缝背核、中缝正中核、中缝桥核、中缝大核、中缝隐核和中缝苍白核）、巨细胞网状核α部、延髓网状结构的内侧部和外侧部、延髓外侧网状核、三叉神经脊束核尾侧亚核和孤束核。５┐羟色胺（５┐ＨＴ）样、Ｐ物质（ＳＰ）样和亮氨酸脑啡肽（Ｌ┐ＥＮＫ）样阳性神经元主要见于中脑导水管周围灰质、脑干中缝核簇和巨细胞网状核α部;此外,ＳＰ样和Ｌ┐ＥＮＫ样阳性神经元还见于臂旁核、背外侧被盖核和孤束核。ＦＧ逆标并呈５┐ＨＴ样、ＳＰ样或Ｌ┐ＥＮＫ样阳性的双标神经元也主要见于中脑导水管周围灰质、脑干中缝核簇和巨细胞网状核α部,尤其是位于延髓中缝核团内的双标神经元数量较多。本研究的结果说明ＳＲＤ内的５┐ＨＴ样、ＳＰ样和Ｌ┐ＥＮＫ样阳性终末主要来自中脑导水管周围灰质、脑干中缝核簇和巨细胞网状核α部,向ＳＲＤ发出５┐ＨＴ能、ＳＰ能和Ｌ┐ＥＮＫ能投射的上述核团对ＳＲＤ发挥“弥漫性伤害抑     

Neurophysiological mechanisms of the reflex lacrimation

Neurophysiological mechanisms of the reflex lacrimation were analyzed in anesthetized rabbits. The secretory pattern of the lacrimation elicited by stimulation of the cornea consisted of two phases, that is, a rapid flow phase during stimulation and the subsequent slow flow phase in post-stimulus time. Parasympathetic nerve activities are closely related to the secretory volume in the rapid flow phase of the reflex lacrimation. On the other hand, excitation of the sympathetic nerve depressed the secretion in the rapid flow phase, while it facilitated slightly the secretion in the slow flow phase. The postganglionic parasympathetic fibers innervating the lacrimal gland showed two responses, i.e., the early and late discharges, when a single electrical shock was applied to the cornea. Their latencies were 68.7 +/- 8.7 msec and 173.3 +/- 14.2 msec, respectively. The threshold of the late response was about 10 times greater than that of the early one. With moderate anesthesia by pentobarbital or with transection of lateral 1/3 of medulla oblongata at the rostral level of the subnucleus caudalis of the spinal trigeminal nucleus, the late response was abolished whereas the early one was left almost unaffected. It is assumed that the early response is elicited by afferent impulses transmitted via the rostral part of the trigeminal sensory nuclear complex and the late one via the caudal part of the complex and also possibly the reticular formation.     

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fos-positive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

Collateral projections from trigeminal sensory nuclei to ventrobasal thalamus and cerebellar cortex in rats

The retrograde fluorescent labeling technique reveals that trigeminal projections to the ventroposteromedial nucleus of the thalamus (VPM) of the rat originate from the main sensory nucleus (MSN) of the trigeminal and subnuclei interpolaris (V1) and caudalis (Vc) of the spinal trigeminal nucleus. These projections are predominantly contralateral; however, the presence of a few ipsilateral labeled cells in MSN suggests an uncrossed trigeminothalamic pathway. Trigeminocerebellar fibers projecting to the paramedian lobule (PML) of the cerebellar cortex are located in Vi and caudal subnucleus oralis (Vo). This is principally an ipsilateral pathway, but several bisbenzimide-labeled cells are present in contralateral Vi. The most notable finding occurred after paired injections of Evans Blue into VPM and bisbenzimide into PML, demonstrating neurons in Vi with divergent projections to both structures. The presence of this type of projection was not found in mice (Steindler: J. Comp. Neurol. 237:155-175, 1985) and has not been reported in other species.