Systemic administration of α-lipoic acid suppresses excitability of nociceptive wide-dynamic range neurons in rat spinal trigeminal nucleus caudalis.

Although a modulatory role has been reported for α-lipoic acid (LA) on T-type Ca2+ channels in the nervous system, the acute effects of LA in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous LA administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from seventeen SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was significantly and dose-dependently inhibited by LA (1-100 mM, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 5 min. These inhibitory effects lasted for approximately 10 min. These results suggest that acute intravenous LA administration suppresses trigeminal sensory transmission, including nociception, via possibly blocking T-type Ca2+ channels. LA may be used as a therapeutic agent for the treatment of trigeminal nociceptive pain.

The dietary constituent resveratrol suppresses nociceptive neurotransmission via the NMDA receptor.

Background Although we have previously reported that intravenous resveratrol administration inhibits the nociceptive neuronal activity of spinal trigeminal nucleus caudalis neurons, the site of the central effect remains unclear. The aim of the present study was to examine whether acute intravenous resveratrol administration in the rat attenuates central glutamatergic transmission of spinal trigeminal nucleus caudalis neurons responding to nociceptive mechanical stimulation in vivo, using extracellular single-unit recordings and microiontophoretic techniques. Results Extracellular single-unit recordings using multibarrel electrodes were made from the spinal trigeminal nucleus caudalis wide dynamic range neurons responding to orofacial mechanical stimulation in pentobarbital anesthetized rats. These neurons also responded to iontophoretic application of glutamate, and the evoked neuronal discharge frequency was significantly increased in a current-dependent and reversible manner. The mean firing frequency evoked by the iontophoretic application of glutamate (30, 50, and 70 nA) was mimicked by the application of 10 g, 60 g, and noxious pinch mechanical stimulation, respectively. The mean firing frequency of spinal trigeminal nucleus caudalis wide dynamic range neurons responding to iontophoretic application of glutamate and N-methyl-D-aspartate were also significantly inhibited by intravenous administration of resveratrol (2 mg/kg) and the maximal inhibition of discharge frequency was observed within 10 min. These inhibitory effects lasted approximately 20 min. The relative magnitude of inhibition by resveratrol of the glutamate-evoked spinal trigeminal nucleus caudalis wide dynamic range neuronal discharge frequency was similar to that for N-methyl-D-aspartate iontophoretic application. Conclusion These results suggest that resveratrol suppresses glutamatergic neurotransmission of the spinal trigeminal nucleus caudalis neurons responding to nociceptive mechanical stimulation via the N-methyl-D-aspartate receptor in vivo, and resveratrol may be useful as a complementary or alternative therapeutic agent for the treatment of trigeminal nociceptive pain.

Acute intravenous administration of dietary constituent theanine suppresses noxious neuronal transmission of trigeminal spinal nucleus caudalis in rats.

Theanine is a non-dietary amino acid linked to the modulation of synaptic transmission in the central nervous system, although the acute effects of theanine in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The present study investigated whether acute intravenous theanine administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 15 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats, and responses to non-noxious and noxious mechanical stimuli were analyzed. The mean firing frequency of SpVc WDR neurons in response to all mechanical stimuli was dose-dependently inhibited by theanine (10, 50, and 100mM, i.v.) with the maximum inhibition of discharge frequency reached within 5min. These inhibitory effects were reversed after approximately 10min. The relative magnitude of theanine's inhibition of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. Iontophoretic application of l-glutamate induced the mean firing frequency of SpVc WDR neuron responding to noxious mechanical stimulation was also inhibited by intravenous administration of 100mM theanine. These results suggest that acute intravenous theanine administration suppresses glutaminergic noxious synaptic transmission in the SpVc, implicating theanine as a potential complementary and alternative therapeutic agent for the treatment of trigeminal nociceptive pain.

Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis.

Although we recently reported that intravenous administration of resveratrol suppresses trigeminal nociception, the precise peripheral effect of resveratrol on nociceptive and non-nociceptive mechanical stimulation-induced trigeminal neuron activity in vivo remains to be determined. The aim of the present study was to investigate whether local subcutaneous administration of resveratrol attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis (SpVc) neuron activity in rats, in vivo. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuron activity in response to orofacial mechanical stimulation in pentobarbital-anesthetized rats. Neurons responded to non-noxious and noxious mechanical stimulation applied to the orofacial skin. Local subcutaneous administration of resveratrol (1-10mM) into the orofacial skin dose dependently and significantly reduced the mean number of SpVc WDR neurons firing in response to both non-noxious and noxious mechanical stimuli, with the maximal inhibition of discharge frequency in response to both stimuli being seen within 5min. These inhibitory effects were no longer evident after approximately 20min. The mean magnitude of inhibition by resveratrol (10mM) of SpVc neuron discharge frequency was almost equal to that of the local anesthetic 1% lidocaine (37mM). These results suggest that local injection of resveratrol into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via inhibition of Na(+) channels in the nociceptive nerve terminals of trigeminal ganglion neurons. Therefore, local subcutaneous administration of resveratrol may provide relief of trigeminal nociceptive pain, without side effects, thus contributing to the suite of complementary and alternative medicines used as local anesthetic agents.

Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C) remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG), into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project) than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project). These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

Sensory sciatic nerve afferent inputs to the dorsal lateral medulla in the rat.

Investigations show the paratrigeminal nucleus (Pa5) as an input site for sensory information from the sciatic nerve field. Functional or physical disruption of the Pa5 alters behavioral and somatosensory responses to nociceptive hindpaw stimulation or sciatic nerve electrostimulation (SNS), both contralateral to the affected structure. The nucleus, an input site for cranial and spinal nerves, known for orofacial nociceptive sensory processing, has efferent connections to structures associated with nociception and cardiorespiratory functions. This study aimed at determining the afferent sciatic pathway to dorsal lateral medulla by means of a neuronal tract-tracer (biocytin) injected in the iliac segment of the sciatic nerve. Spinal cord samples revealed bilateral labeling in the gracile and pyramidal or cuneate tracts from survival day 2 (lumbar L1/L2) to day 8 (cervical C2/C3 segments) following biocytin application. From day 10 to day 20 medulla samples showed labeling of the contralateral Pa5 to the injection site. The ipsilateral paratrigeminal nucleus showed labeling on day 10 only. The lateral reticular nucleus (LRt) showed fluorescent labeled terminal fibers on day 12 and 14, after tracer injection to contralateral sciatic nerve. Neurotracer injection into the LRt of sciatic nerve-biocytin-treated rats produced retrograde labeled neurons soma in the Pa5 in the vicinity of biocytin labeled nerve terminals. Therefore, Pa5 may be considered one of the first sites in the brain for sensory/nociceptive inputs from the sciatic nerve. Also, the findings include Pa5 and LRt in the neural pathway of the somatosympathetic pressor response to SNS and nocifensive responses to hindpaw stimulation.

Medullary dorsal horn neurons providing axons to both the parabrachial nucleus and thalamus.

It has often been suggested that the trigemino- and spino-thalamic pathways are highly implicated in sensory-discriminative aspects of pain, whereas the trigemino- and spino-parabrachial pathways are strongly implicated in affective/emotional aspects of pain. On the other hand, the superficial laminae of the spinal dorsal horn, where many nociceptive neurons are distributed, have been reported to contain projection neurons innervating both the parabrachial nucleus (PBN) and thalamus by way of axon collaterals (Hylden et al., 1989). For the medullary dorsal horn (caudal subnucleus of spinal trigeminal nucleus: Vc), however, the existence of such neurons has not been reported. Thus, in the present study, we examined whether the Vc might contain projection neurons sending their axons to both the thalamus and PBN. Dual retrograde labeling with fluorescence dyes was attempted. In each rat, tetramethylrhodamine-dextran amine and Fluoro-gold were stereotaxically injected into the PBN and thalamic regions, respectively. The proportion of the dually labeled Vc cells in the total population of all labeled Vc cells was about 20%. More than 90% of the dually labeled neurons were distributed in lamina I (marginal zone), less than 10% of them were located in lamina II (substantia gelatinosa), and only a few (about 1%) were found in lamina III (magnocellular zone). The results indicate that some Vc neurons in the superficial laminae mediate nociceptive information directly to the PBN and thalamus by way of axon collaterals and that the vast majority of them project to the ipsilateral PBN and contralateral thalamus.

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.

Projections from subnucleus oralis of the spinal trigeminal nucleus to contralateral thalamus via the relay of juxtatrigeminal nucleus and dorsomedial part of the principal sensory trigeminal nucleus in the rat.

Following injection of HRP into contralateral thalamus, retrogradely labeled cells were observed in principal sensory trigeminal nucleus (Vp) and an area of juxtatrigeminal nucleus (JX) formerly described by John and Tracey (1987). When PHA-L was delivered to dorsomedial part of the subnucleus oralis (Vodm), PHA-L labeled terminals were seen in dorsomedial part of the Vp (Vpdm) and in the JX region. Comparing the distribution of PHA-L labeled terminal field with that of HRP labeled JX neurons showed that the labeled terminals and neurons were overlapped closely in the JX. The distribution patterns of the labeled terminals and JX neurons were also the same: viewed on the coronal planes caudal-rostrally, both of the labelings began to appear at the levels where the facial nerve root was just broken. Rostrally, at middle levels of the motor trigeminal nucleus (Vmo), the labelings showed their typical view covering dorsal and ventral JX (dJX, vJX). The labelings disappeared at rostral poles of the Vmo and Vp. When injections of PHA-L into the Vodm and HRP into the contralateral thalamus was made in one rat, the contacts between Vodm projecting terminals labeled with PHA-L and HRP labeled trigemino-thalamic neurons were seen in the JX and also in the Vpdm. Then, electron microscopic (EM) study was done, injections of kainic acid into the Vodm and HRP into the contralateral thalamus was performed simultaneously. After EM embedding, the JX and Vpdm regions were selected, ultrathin sections were cut and observed with EM. In both areas, axo-somatic and axo-dendritic synapses were seen between degenerated boutons and HRP labeled somata or dendrites. Namely, the Vodm projecting terminals synapsed on trigemino-thalamic neurons in the JX and Vpdm. Anyway, axo-dendritic synapses was the main type of observed synapses. Thus, the present work demonstrated 1. the JX containing a group of trigemno-thalamic neurons was a target of special projections froin the Vodm; 2. The Vodm neurons projected to the contralateral thalamus through the relay of JX and Vpdm neurons.

Preprodynorphin-like immunoreactivity in medullary dorsal horn neurons projecting to the thalamic regions in the rat.

Preprodynorphin (PPD)-like immunoreactive (-LI) neuronal cell bodies in the trigeminal sensory nuclear complex of the rat were found in laminae I and II of the medullary dorsal horn (MDH; caudal spinal trigeminal nucleus) and the paratrigeminal nucleus. A PPD immunofluorescence histochemistry combined with a fluorescence retrograde tract-tracing method revealed that some of the PPD-LI neurons in the MDH and paratrigeminal nucleus projected to the thalamic regions. Nociceptive nature of the PPD-LI MDH neurons projecting to the thalamic regions was also demonstrated by a triple labeling method, using the technique of the noxious stimulus-evoked expression of the immediate-early gene, c-fos. In the rats which were subcutaneously injected with formalin into the upper and lower lips, c-fos protein (Fos) was found in PPD-LI neurons which were labeled with a retrograde tracer injected into the thalamic regions.

Efferent and collateral organization of paratrigeminal nucleus projections: an anterograde and retrograde fluorescent tracer study in the rat.

The paratrigeminal nucleus (PTN) receives primary visceral afferent projections through cranial nerves IX and X and somatic afferent projections through cranial nerve V and dorsal roots as far caudally as C7. Pressure injections of the anterograde tracer tetramethylrhodamine dextran into the PTN in the rat resulted in bilateral labeling in the nucleus of the tractus solitarius, dorsal motor nucleus of the vagus nerve, and parabrachial nucleus. Anterograde labeling in the parabrachial nucleus was strongest in the external medial, external lateral, and ventral lateral subnuclei. Anterograde labeling was also found in the contralateral paratrigeminal nucleus, lamina I of the spinal trigeminal nucleus subnucleus caudalis, and ventroposteromedial nucleus of the thalamus. The collateral organization of PTN neurons was demonstrated by injecting different fluorescent retrograde tracers into the terminal fields of PTN projections as determined by the anterograde tracing experiments. Double-labeled neurons were found in the paratrigeminal nucleus following all combinations of injection sites. The most prominent PTN efferent projections and the most highly collateralized were to the nucleus of the tractus solitarius and parabrachial nucleus. The efferent and collateral connections of the paratrigeminal nucleus may provide a neuroanatomical substrate for integrating convergent visceral and somatic afferent information used to modulate autonomic function and behavior related to thermoregulation, nociception, and gustation.

The NMDA receptor antagonist MK-801 reduces Fos-like immunoreactivity in central trigeminal neurons and blocks select endocrine and autonomic responses to corneal stimulation in the rat.

The N-methyl-D-aspartate (NMDA) receptor is implicated in multiple aspects of pain processing by the central nervous system. However, the role of NMDA receptors in the endocrine and autonomic aspects of nociception remains uncertain. The present study examined the influence of the NMDA receptor antagonist, MK-801 (0.02-2.0 mg/kg, intracarotid), on the adrenal and autonomic responses to corneal stimulation (mustard oil, 20% sol.) in barbiturate-anesthetized rats. Fos-like immunoreactivity (Fos-LI) evoked by corneal stimulation was quantified within the spinal trigeminal nucleus (Vsp) of MK-801 pretreated animals to assess activation of central trigeminal neurons. Corneal stimulation-evoked increases in the plasma concentrations of adrenocorticotropin (ACTH), epinephrine and norepinephrine were reduced dose-dependently by MK-801. Plasma ACTH also increased after moderate hemorrhage, a response that was not affected by MK-801. MK-801 did not reduce the magnitude of corneal stimulation-evoked increases in arterial pressure and heart rate; however, prestimulus arterial pressure was reduced by drug treatment. Fos-LI was distributed bimodally within the ipsilateral caudal Vsp: one peak of Fos-LI in the subnucleus interpolaris/caudalis transition region and a second peak within the superficial laminae of the subnucleus caudalis/upper cervical cord transition region. The magnitude of both peaks of Fos-LI was reduced dose-dependently by MK-801. These results indicate a significant contribution from NMDA receptors in control of select endocrine and autonomic responses that accompany trigeminal nociception and in activation of central trigeminal neurons that process corneal nociceptive input.

Localization of an isoform of carboxylesterase in rat brain differs from that in human brain.

Liver carboxylesterase (CE) is an enzyme capable of metabolizing drugs, and may also function as a regulator of lipid metabolism. We examined two isoforms of CE (RH1 and RL1) by immunohistochemistry in rat brain. The anti-RL1 antibody did not stain any brain structures. The anti-RH1 antibody, however, stained oligodendrocytes in all brain tissues and tanycytes, as well as some neurons in the deep cingulate gyrus, various hypothalamic nuclei and the spinal trigeminal nucleus. In the central nervous system, rat CE may function as a protective factor against foreign chemicals in these glial and neuronal cells. The distribution differed from that of the homologous human isoform which has been previously found only in endothelial cells in human brain. A possible relation between RH1 positive neurons and the medial pain system is discussed.

Differential NMDA NR1 mRNA expression among spinal trigeminal neurons that project to different targets.

The N-methyl-D-aspartate (NMDA) NR1 glutamate receptor subtype has been proposed to play an important role in the transmission of orofacial sensory information in the spinal trigeminal nucleus (STN). The distribution of NR1 mRNA expression in the STN and its relationship to STN projection neurons has not been investigated previously. Using neuroanatomical tract tracing with in situ hybridization techniques, we found that neurons in the STN that project to the thalamus, cerebellum and spinal cord expressed more mRNA for NR1 than do nonprojection neurons. Trigeminothalamic neurons were found to express more NR1 mRNA than trigeminospinal or trigeminocerebellar neurons. Thus, NMDA-specific excitatory amino acids may be more efficacious in the relay of orofacial information to the thalamus than to the spinal cord or cerebellum.

Modulation of glycine receptor chloride channels by cAMP-dependent protein kinase in spinal trigeminal neurons.

Glycine is an important inhibitory transmitter in the brainstem and spinal cord. In the trigeminal subnucleus caudalis (medullary dorsal horn) and in the spinal dorsal horn (the relaying centres for processing pain and sensory information), glycine inhibits the glutamate-evoked depolarization and depresses firing of neurons. The binding of glycine to its receptor produces a large increase in Cl- conductance, which causes membrane hyperpolarization. The selectivity and gating properties of glycine receptor channels have been well characterized; the glycine receptor molecules have also been purified. The amino-acid sequence, deduced from complementary DNA clones encoding one of the peptides (the 48K subunit), shows significant homology with gamma-aminobutyric acid A (GABAA) and nicotinic acetylcholine receptor subunits, suggesting that glycine receptors may belong to a superfamily of chemically gated channel proteins. However, very little is known about the modulation of glycine receptor channels. We have investigated the regulation of strychnine-sensitive glycine receptor channels by cyclic AMP-dependent protein kinase in neurons isolated from spinal trigeminal nucleus of rat and report here that the protein kinase A dramatically increased the glycine-induced Cl- currents by increasing the probability of the channel openings. GS protein, which is sensitive to cholera toxin, was involved in the modulation.

Ultrastructural and neurochemical analysis of synaptic input to trigemino-thalamic projection neurones in lamina I of the rat: a combined immunocytochemical and retrograde labelling study.

The synaptology of lamina I thalamic projection neurones in the spinal trigeminal nucleus of the rat was investigated by combining electron microscopic immunocytochemistry with the retrograde transport of horseradish peroxidase. Fifteen retrogradely labelled neurones were serially sectioned and their dendrites were traced for up to 160 microns in order to characterise the synaptic input to their cell bodies and proximal dendrites. Projection neurones receive synapses from dome-shaped substance P and enkephalin immunoreactive terminals, which make simple axosomatic or axodendritic synapses. In addition, the cells receive synapses from numerous nonimmunoreactive terminals including a wide range of different dome-shaped terminals and various scalloped or glomerular terminals. Dome-shaped terminals synapse with small stubby spines in addition to cell bodies or dendritic shafts and they are probably derived from lamina II interneurones and from descending bulbospinal pathways. Glomerular terminals occur in two main classes: small type A terminals with dark axoplasm and larger type B terminals. Type B terminals participate in synaptic triads in which a peripheral terminal synapses both axoaxonically with the glomerular terminal and axodendritically with the projection neurone. Type A and type B terminals closely resemble the central terminals of spinal cord lamina II glomeruli and are probably derived from C and A delta I degrees afferent fibers. The results indicate that lamina I projection neurones are under pre- and postsynaptic control from diverse sources. Their complex synaptic organisation highlights the key role that such cells play in the rostrad transmission of somatosensory information.

Neuronal activities in ventrobasal complex of thalamus and in trigeminal main sensory nucleus during EEG desynchronization in anesthetized rats.

Activities of somatosensory relay neurons responding to orofacial mechanical stimulation were examined in the ventrobasal complex of the thalamus (VB) and in the trigeminal main sensory nucleus (MSN) during EEG desynchronization in urethane-anesthetized rats. EEG desynchronization was induced by scrotal warming in a temperature range of 35-40 degrees C. Responses of most VB neurons to receptive-field stimulation were augmented during EEG desynchronization, when compared to responses during synchronization. Spontaneous activity of VB neurons also increased with EEG desynchronization. Responses of MSN neurons to receptive-field stimulation did not change appreciably when the EEG pattern was altered. If a VB neuron was induced by iontophoretic application of glutamate to fire at the same rate as seen during EEG desynchronization, a similar increased response to receptive-field stimuli was also observed. The augmented response of the VB neuron during desynchronization may thus have resulted from increased excitability of the neuron itself.

The properties of cells in the cat trigeminal main sensory and spinal subnuclei activated by mechanical stimulation of the periodontium.

Neurophysiological exploration of the trigeminal sensory complex was done on 42 cats under ketamine anaesthesia, paying special attention to units receiving a periodontal input. Among 492 cells recorded in the trigeminal sensory complex, 73 responded to mechanical stimulation of the periodontium and were precisely localized histologically. Thalamic stimulation was also delivered to the ipsi and contralateral ventro-posterior nucleus to test for antidromic responses. Results of this systematic study were plotted on reference drawings of the full extent of the trigeminal sensory complex.