Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 19 recordsLinked to original sources

PubMed2007

Prostaglandin E2 potentiates the excitability of small diameter trigeminal root ganglion neurons projecting onto the superficial layer of the cervical dorsal horn in rats.

The aim of the present study was to investigate how prostaglandin E2 (PGE2) affects the excitability of trigeminal root ganglion (TRG) neurons, projecting onto the superficial layer of the cervical dorsal horn, using fluorescence retrograde tracing and perforated patch-clamp techniques. TRG neurons were retrogradely labeled with fluorogold (FG). The cell diameter of FG-labeled neurons was small (< 30 microm). Under the voltage-clamp mode, application of PGE2 (0.01-10 microM) concentration-dependently increased the magnitude of the peak tetrodotoxin-resistant sodium current (TTX-R I(Na)) and this current was maximal at a concentration of 1 microM. One micromolar PGE2 application caused a hyperpolarizing shift of 8.3 mV in the activation curve for TTX-R I(Na). In the current-clamp mode, the PGE2 (1 microM) application significantly increased the number of action potentials during the depolarizing step pulses as well as the level of overshoot but had no significant effect on the resting membrane potential. These results suggest that the excitability of small diameter TRG neurons seen after 1 microM PGE2 application is involved in an increase in the

Action Potentials↗

PubMed2006

Neurohormones as putative circadian clock output signals in the central nervous system of two cricket species.

Antisera to the neuropeptides corazonin (Crz) and crustacean cardioactive peptide (CCAP) and to the diapause hormone (DH) react with small sets of neurones in the cephalic ganglia of the crickets Dianemobius nigrofasciatus and Allonemobius allardi. The distribution of their immunoreactivities is similar in the two species and overlaps with the locations of presumed circadian clock components in the optic lobes, protocerebrum, tritocerebrum, suboesophageal ganglion (SOG) and frontal ganglion. D. nigrofasciatus contains two Crz-immunoreactive (Crz-ir) cells in each optic lobe, six cell groups in the protocerebrum, four in the tritocerebrum, and one in SOG, whereas A. allardi harbours only five Crz-ir groups in the protocerebrum and four in the tritocerebrum. CCAP immunoreactivity occurs in both species in four protocerebrum cell clusters, four tritocerebrum cell clusters, four SOG cell clusters, one frontal ganglion cell cluster, and two optic lobe cell clusters; D. nigrofasciatus possesses two additional cells with unique links to the lamina in the optic lobe. DH-related antigens are present in four cell clusters in the optic lobe, six (D. nigrofasciatus) or eight (A. allardi) in the protocerebrum, four in the tritocerebrum, and three (A. allardi) or five (D. nigrofasciatus) in the SOG. Some of the detected cells also react with antibody to the clock protein Period (PER) or lie close to PER-ir cells. Crickets reared at two different photoperiods do not differ in the distribution and intensity of immunoreactivities. No changes have been detected during the course of diurnal light/dark cycles, possibly because the antisera react with persistent prohormones, whereas circadian fluctuations may occur at the level of their processing or of hormone release. The projection of immunoreactive fibres to several brain regions, the stomatogastric nervous system and the neurohaemal organs indicates multiple functions of the respective hormones.

Animals↗

PubMed2006

Electromyography of the cricoarytenoid unit during supracricoid laryngectomy with a cricohyoidoepiglottopexy procedure.

Two patients who received supracricoid laryngectomy with cricohyoidoepiglottopexy to treat laryngeal cancers, underwent intra-operative electromyography analysis. After the lesion was removed and the electrodes were inserted into the remaining intrinsic laryngeal muscles, the depth of anaesthesia was carefully reduced. Gentle tactile stimulations were applied to the pharynx to trigger the reflex movement of the remaining arytenoids. Recordings were made when reflex movement was achieved. Case one: Electromyography (EMG) of the remaining arytenoid demonstrated clear phase differences indicating reciprocal activities between the adductor group (lateral cricoarytenoid muscle, interarytenoid muscle) and the abductor muscle (posterior cricoarytenoid muscle). Case two: EMG of the remaining arytenoid demonstrated reciprocal activities between the interarytenoid muscle and the posterior cricoarytenoid muscle. Activity of the lateral cricoarytenoid muscle was not evident because the muscle was excised during removal of the paraglottic space. Mobility of the arytenoid was attributed to interaction between the interarytenoid muscle and posterior cricoarytenoid muscle. Reciprocal interaction between the interarytenoid muscle and posterior cricoarytenoid muscle alone is also capable of maintaining post-operative laryngeal functions after supracricoid laryngectomy with cricohyoidoepiglottopexy.

Aged↗

PubMed2006

Right parietal activation during delusional state in episodic interictal psychosis of epilepsy: a report of two cases.

Magnetoencephalography (MEG) was used to image brain activity associated with delusions in episodic interictal psychosis of epilepsy. Two female patients aged 65 and 68 with temporal lobe epilepsy were studied during and after a delusional state. Topographic images of the excess kurtosis (g2), the statistical index of spikelike activity, were obtained from unaveraged MEG recordings using an analysis called "synthetic aperture magnetometry" (SAM). For both patients, MEG waveforms and excess kurtosis images revealed spiky activity in the right inferior parietal region during the delusional state. A second MEG measurement after delusions were resolved with antipsychotic therapy revealed no excess kurtosis in the right parietal area. Likewise, the sharp waves on MEG recordings disappeared as well. Our results suggest association of the right inferior parietal cortex, including the supramarginal gyrus, with the delusional state of episodic interictal psychosis of epilepsy.

Aged↗

PubMed2006

Submandibular abscess caused by Salmonella.

Salmonella species represent uncommon causative agents in focal infections of the head and neck. This article presents a rare case of Salmonella submandibular abscess in a 59-year-old patient with diabetes mellitus, chronic hepatitis and liver cirrhosis. The patient was successfully treated with drainage of the abscess and oral administration of quinolone. An immunocompromised condition can be a critical predisposing factor for Salmonella submandibular abscess.

Abscess↗

PubMed2006

Activation of alpha2-adrenoreceptors suppresses the excitability of C1 spinal neurons having convergent inputs from tooth pulp and superior sagittal sinus in rats.

The aim of the present study was to test the hypothesis that activation of alpha(2)-adrenoreceptors modulates the excitability of C1 neurons having convergent inputs from both the tooth pulp (TP) and the superior sagittal sinus (SSS), by using the microiontophoretic techniques of drug application and immunohistochemical approaches. Extracellular single-unit recordings were made from 38 C1 neurons responding to electrical stimulation of TP under pentobarbital-anesthetized rats. Seventy-one percent of C1 neurons (27/38) that responded to TP stimulation also responded to electrical stimulation of the SSS. In these neurons, L: -glutamate-evoked C1 neuronal discharge firings were increased in a dose-dependent manner. The mean glutamate-evoked firing rates were dose-dependently inhibited after microiontophoretic application of clonidine (alpha(2)-adrenoreceptor/imidazoline I(1) receptor agonist). The inhibition of glutamate-evoked C1 mean firings by clonidine was antagonized by the co-application of idazoxan (alpha(2)-adrenoreceptor/imidazoline I(2) receptor antagonist), yohimbine (alpha(2)-adrenoreceptor) but not the alpha(1)-adrenoreceptor antagonist, prazosin with affinity for alpha(2B)- and alpha(2C)-adrenoreceptors. The mean spontaneous discharge frequencies were significantly inhibited by the microiontophoretic application of clonidine and this inhibition was reversed by the co-application of idazoxan, yohimbine. Microiontophoresis of clonidine also resulted in a reduction of TP-/SSS-evoked activity and this effect was reversed by the co-application of yohimbine. Immunoreactivity for alpha(2A)-adrenoreceptor was found in the superficial layers of I-III in the C1 region. These results suggest that alpha(2)-adrenoreceptor agonist clonidine inhibits the excitability of C1 neurons having convergent inputs from TP and SSS afferents, and that the activation of alpha(2A)-adrenoreceptors onto C1 dorsal horn neurons may contribute as a useful therapeutic target for the alleviation of trigeminal referred pain associated with migraine and tooth pain.

Action Potentials↗

PubMed2006

Enhanced excitability of rat trigeminal root ganglion neurons via decrease in A-type potassium currents following temporomandibular joint inflammation.

The aim of the present study was to investigate the effect of temporomandibular joint inflammation on the excitability of trigeminal root ganglion neurons innervating the temporomandibular joint using a perforated patch-clamp technique. Inflammation was induced by injection of complete Freund's adjuvant into the rat temporomandibular joint. The threshold for escape from mechanical stimulation in the temporomandibular joint-inflamed rats was significantly lower than that in control rats. Fluorogold labeling was used to identify the trigeminal root ganglion neurons innervating the site of inflammation. When voltage-clamp (V(h)=-60 mV) conditions were applied to these Fluorogold-labeled small diameter trigeminal root ganglion neurons (<30 mum), voltage-dependent transient K(+) current densities were significantly reduced in the inflamed rats compared with controls. In addition, the voltage-dependence of inactivation of the voltage-dependent transient K(+) current was negatively shifted in the labeled temporomandibular joint-inflamed trigeminal root ganglion neurons. Furthermore, temporomandibular joint inflammation significantly reduced the threshold current and significantly increased action potential firings evoked at two-fold threshold in the Fluorogold-labeled small trigeminal root ganglion neurons. Application of 4-aminopyridine (0.5mM) to control trigeminal root ganglion neurons mimicked the changes in the firing properties observed after complete Freund's adjuvant treatment. Together, these results suggest that temporomandibular joint inflammation increases the excitability of trigeminal root ganglion neurons innervating temporomandibular joint by suppressing voltage-dependent transient K(+) current via a leftward shift in the inactivation curve. These changes may contribute to trigeminal inflammatory allodynia in temporomandibular joint disorder.

4-Aminopyridine↗

PubMed2006

Invasive growth of hepatic angiomyolipoma; a hitherto unreported ominous histological feature.

AIMS: Although histological features of hepatic angiomyolipoma (AML) are highly variable, true malignant change is extremely rare. The aim was to review the histological features of invasive growth and clinical outcomes in 39 cases of hepatic AML. METHODS AND RESULTS: An invasive growth pattern into surrounding hepatic parenchyma, portal triads and/or around hepatic veins was found in 24 of 39 tumours (62%). One variant showed tumour cells replacing hepatocytes within the liver cell cords. The other consisted of portal or perivascular invasive growth along blood vessels. In the former pattern, small isolated tumour cell clusters were occasionally found in the vicinity of the main mass, showing a sprouting pattern. Although these histological features suggest malignancy, distant metastases were not found in any of the cases within a mean follow-up period of 6.8 years. CONCLUSIONS: A previously unrecognized histological feature of an invasive growth pattern, which suggests malignancy and might promote an erroneous diagnosis, was frequently found in hepatic AMLs. However, among about 180 reported hepatic AMLs, including the present cases, only one hepatic AML with distant metastasis has been reported to date and nearly all hepatic AMLs behave in a benign fashion. Therefore, pathologists should not overdiagnose malignancy based solely on the histological invasive growth patterns described in this paper.

Adult↗

PubMed2006

Cloning and expression analysis of takeout/JHBP family genes of silkworm, Bombyx mori.

A Bombyx EST cDNA database was searched using the Drosophila takeout gene and nine cDNAs were obtained. The homology search suggested that these genes are widespread in insects and organize a large gene family, and that they have hydrophobic ligands. A phylogenetic tree indicated that the genes are first divided into two large groups, juvenile hormone binding protein and other protein genes, and the latter group diversified within a short time at an early stage. The expression study of five Bombyx genes indicated that they are expressed in various tissues and are regulated by development and feeding conditions. The Bombyx genes might have roles related to the regulation of metabolism, growth or development related to nutritional conditions.

Amino Acid Sequence↗

PubMed2006

Enhanced solubilization of rock phosphate by Penicillium bilaiae in pH-buffered solution culture.

Little is known about how pH-buffering capacity affects phosphorus (P) solubilization by Penicillium bilaiae. This study compared solubilization of rock phosphate (RP) by P. bilaiae in nonbuffered (pH 5.0) and buffered (pH 7.0) media. Fungal growth reached the stationary phase around day 12 and was slightly enhanced in the buffered medium. The fungus reduced solution pH from 5.0 to 4.1 in the nonbuffered medium and from 7.0 to 4.9 in the buffered medium by day 12. Phosphorus concentrations increased after day 9 more in the buffered than in the nonbuffered media (53 and 5 mg P x L(-1), respectively, on day 12). On day 12, higher concentrations of citric and oxalic acids were detected in the buffered (2.0 and 1.2 g x L(-1), respectively) than nonbuffered media (0.5 and 0.04 g x L(-1), respectively). Solubilization of RP was simulated without P. bilaiae in solutions equivalent to the nonbuffered and buffered cultures of P. bilaiae grown with RP. After a 24 h incubation, the P concentrations were of similar magnitudes to those observed in the P. bilaiae culture (18 and 47 mg P x L(-1), respectively, in the nonbuffered and buffered media). Under increased pH-buffering conditions, the enhanced production of citric and oxalic acids led to significant RP solubilization.

Calcium Phosphates↗

PubMed2005

Alpha-synuclein-positive structures induced in leupeptin-infused rats.

Abnormal accumulation of alpha-synuclein is regarded as a key pathological step in a wide range of neurodegenerative processes, not only in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but also in multiple-system atrophy (MSA). Nevertheless, the mechanism of alpha-synuclein accumulation remains unclear. Leupeptin, a protease inhibitor, has been known to cause various neuropathological changes in vivo resembling those of aging or neurodegenerative processes in the human brain, including the accumulation of neuronal processes and neuronal cytoskeletal abnormalities leading to neurofibrillary tangle (NFT)-like formations. In the present study, we administered leupeptin into the rat ventricle and found that alpha-synuclein-positive structures appeared widely in the neuronal tissue, mainly in neuronal processes of the fimbria and alveus. Immunoelectron microscopic study revealed that alpha-synuclein immunoreactivity was located in the swollen axons of the fimbria and alveus, especially in the dilated presynaptic terminals. In addition colocalization of alpha-synuclein with ubiquitin was rarely observed in confocal laser-scan image. This is the first report of experimentally induced in vivo accumulation of alpha-synuclein in non-transgenic rodent brain injected with a well-characterized protease inhibitor by an infusion pump. The present finding suggests that the local accumulation of alpha-synuclein might be induced by the impaired metabolism of alpha-synuclein, which are likely related to lysosomal or ubiquitin-independent proteasomal systems.

Animals↗

PubMed2005

Role of capsaicin-sensitive primary afferent inputs from the masseter muscle in the C1 spinal neurons responding to tooth-pulp stimulation in rats.

The aim of the present study was to demonstrate the convergence of inputs from masseter muscle (MM) and tooth pulp (TP) onto C1 spinal neurons and to determine whether the afferent fibers express the functional vanilloid receptor (VR1). Extracellular single-unit recordings were made from 61 C1 units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram signal in pentobarbital anesthetized rats. Eighty-four percent of C1 neurons responding to TP stimulation also responded to the ipsilateral MM stimulation. Of these neurons, 61% were considered to be afferent inputs from Adelta-fibers and the remaining units (39%) were C-fibers, based on calculation of the nerve conduction velocity. Intramuscular injection of capsaicin (0.05 and 0.1%) produced a reduction in a MM-induced C1 neuronal activity in a dose-dependent manner and this effect was antagonized by pretreatment with an antagonist of VR1, capsazepine. Some of these units were also excited by noxious heat stimulation (> 43 degrees C). The trigeminal root ganglion (TRG) neurons that innervated the MM were retrogradely labeled with Fluorogold (FG) and the small-diameter FG-labeled TRG neurons expressed the immunoreactivity for VR1. After intramuscular mustard oil injection (noxious chemical stimulation), the C1 neuronal activity induced by both touch and pinch stimuli was enhanced and their receptive field sizes were significantly expanded. These changes were reversed within 15-20 min. These results suggest that there may be the convergence of noxious afferents inputs from the MM and TP afferents on the same C1 neurons in rats, and that the afferent fibers expressing the functional VR1 may contribute to the hyperalgesia and/or referred pain associated with temporomandibular joint disorder.

Action Potentials↗

PubMed2005

Wavelet-crosscorrelation analysis: Non-stationary analysis of neurophysiological signals.

OBJECTIVE: Wavelet-crosscorrelation analysis is a new application of wavelet analysis used to show the propagation of epileptiform discharges and to localize the corresponding lesions. We have shown previously that this analysis can help predict brain conditions statistically (Mizuno-Matsumoto et al. 2002). Our objective was to assess whether wavelet-crosscorrelation analysis reveals the initiation and propagation of epileptiform activity in human patients. METHODS: The data obtained from three patients with simple partial seizures (SPS) using whole-head magnetoencephalography (MEG) were analyzed by the wavelet-crosscorrelation method. Wavelet-crosscorrelation coefficients (WCC), the coherent structure of each possible pair of signals from 64 MEG channels forvarious periods, and the time lag (TL) in two related signals, were ascertained. RESULTS: We clearly demonstrated both localization of the irritative zone and propagation of the epileptiform discharges. CONCLUSIONS: Wavelet-crosscorrelation analysis can help reveal and visualize the dynamic changes of brain conditions. The method of this analysis can compensate for other existing methods for the analysis of MEG, electroencephalography (EEG) or Elecotrocorticography (ECoG). SIGNIFICANCE: Our proposed method suggests that revealing and visualizing the dynamic changes of brain conditions can help clinicians and even patients themselves better understand such conditions.

Adult↗

PubMed2005

Changes in histology and expression of cytokines and chemokines in the rat lung following exposure to ovalbumin.

Brown Norway (BN) and Fischer 344 (F344) rats were exposed to aerosol of 1% ovalbumin (OVA) solution for 30 min at 1 week after the second sensitization with 1 mg of OVA at 2-week intervals. Changes in the histology and expression of cytokines and chemokines in the lung were examined for up to 96 h after the exposure. The lung weight significantly increased in BN rats but not in F344 rats. Histologically, in the lung of BN rats, multiple foci of hemorrhage in the alveolar space with infiltration of eosinophils and macrophages in the surrounding alveolar septa were first observed. Thereafter, granulomatous lesions developed in the preexisting hemorrhagic foci, finally resulting in formation of multiple eosinophilic granulomas. On the other hand, in F344 rats, infiltration of eosinophils and macrophages was observed around the vessels and bronchi. Thereafter it progressed gradually, resulting in mild thickening of alveolar septa. The levels of Th1- (interferon-gamma and interleukin 2 (IL-2)) and Th2-related cytokines (IL-4 and IL-5) and chemokines (eotaxin and monocyte chemoattractant protein-1) mRNAs measured by reverse transcription-polymerase chain reaction method were elevated in the lung of both strains, and the levels were higher in BN rats than in F344 rats. These results suggest that BN rats are more sensitive to OVA-sensitization/inhalation than F344 rats and that the difference in the severity of lung lesions between BN and F344 rats may reflect the difference in the expression levels of cytokines and chemokines between these two strains.

Animals↗

PubMed2005

Molecular cloning, characterization and regulation of the cockroach vitellogenin receptor during oogenesis.

The vitellogenin receptor (VgR) belongs to the low density lipoprotein receptor (LDLR) superfamily, and mediates the uptake of vitellogenin (Vg) into developing oocytes of all oviparous species. We cloned and characterized a VgR from previtellogenic ovaries of the cockroach, Periplaneta americana (Pa). This is the first report on a VgR from a hemimetabolous insect. The cDNA, comprising 5722 bp, encoded a 1790-residue mature protein with a predicted molecular mass of 200.5 kDa. We next characterized the ovarian expression pattern, developmental regulation and cellular distribution of the VgR mRNA and protein. Northern blot analysis confirmed that a approximately 7.2 kb transcript was specifically expressed in ovarian tissues at high levels throughout ovarian development, especially in previtellogenic ovaries and in ovaries before adult emergence. RNA in situ hybridization and immunocytochemistry localized the VgR mRNA and protein to germ-line derived cells, the oocytes, and revealed that VgR gene transcription and translation begin very early during oocyte differentiation in the germarium. Immunoblot analysis detected an ovary-specific VgR protein of approximately 210 kDa that was present in previtellogenic ovaries on the day of female emergence. The VgR protein signal strengthened every day and was intense after initiation of vitellogenesis and onset of Vg uptake. The immunoblotting of vitellins demonstrated that Vg uptake occurred on day 5, one day after Vg first appeared in the haemolymph, indicating that the receptor-endocytotic machinery starts functioning soon after the ligand becomes available.

Amino Acid Sequence↗

PubMed2004

SAM(g2) analysis for detecting spike localization: a comparison with clinical symptoms and ECD analysis in an epileptic patient.

SAM(g2) analysis, a combination of synthetic aperture magnetometry (SAM) and excess kurtosis (g2) method, is a novel epilepsy analysis procedure based on a spatial filtering technique. By producing a three-dimensional image of the g2 values and superimposing them onto a patient's MR images, this analysis can automatically estimate spike localization from raw MEG epilepsy signals including spikes. The aim of this study is to examine SAM(g2) analysis using MEG signals of an epileptic patient, whose clinical symptoms of colored elementary visual auras had ceased in accordance with the changes of the estimated localizations of the equivalent current dipoles (ECDs) of the interictal spikes. His visual auras were experienced in 1997, while they ceased in 1999 with effective medication. The patient provided written informed consent for the experimental procedures. The MEG signals were recorded in 1997 and 1999, and were analyzed using both ECD and SAM(g2) analyses. For the MEG signals of 1997, ECD analysis estimated most of the interictal spikes in the right fusiform and inferior temporal gyri, which subserve human color processing. SAM(g2) analysis also estimated them in the same areas. For those of 1999, both ECD and SAM(g2) analyses estimated them in the right transverse gyrus of Heschl. As well as ECD analysis, SAM(g2) analysis successfully estimated the changes of the localizations of the interictal spikes in accordance with the changes of the patient's clinical symptoms, indicating that SAM(g2) analysis is useful for detection of interictal spike localization in epileptic patients.

Action Potentials↗

PubMed2004

Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma.

The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.

Adenoma↗

PubMed2004

Activaton of GABAB receptor inhibits the excitability of rat small diameter trigeminal root ganglion neurons.

A selective GABA(B) receptor agonist, baclofen, is known to suppress neuropathic pain. In the present study, we investigated the effect of baclofen on the excitability of trigeminal root ganglion (TRG) neurons by using the whole cell and perforated patch-clamp recording techniques. Under voltage-clamp (V(h)=-60 mV), voltage-dependent K(+) currents were recorded in the small diameter TRG neurons (<30 microm) and isolated by blocking Na(+) and Ca(2+) currents with appropriate ion replacement. Separation of the K(+) current components was achieved by the response to variation in the conditioning voltage. Two distinct K(+) current components, a transient (I(A)) and a sustained (I(k)), were identified. Baclofen significantly increased I(A) by 74.8% (50 microM) and in a dose-dependent manner (1-50 microM). Similarly, I(K) was also enhanced by baclofen administration (41.8%: 50 microM). The relative amplitude of potentiation of I(A) was significantly higher than that of I(K) (P<0.05). Baclofen-sensitive I(A) and I(K) currents were antagonized by K(+) channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The augmentation of K(+) currents was antagonized by 3-amino-2-(4-chlorophenyl)-2-hydroxypropylsulfonic acid (saclofen; GABA(B) antagonist). In the current clamp mode, the resting membrane potential was -62+/-1.6 mV (n=24). Hyperpolarization of the membrane potential was elicited by baclofen (10-50 microM), and the response was associated with a decrease in the input resistance. Baclofen induced-hyperpolarization was blocked by saclofen (100 microM). In the presence of both 4-AP and TEA, no significant changes in membrane potential induced by baclofen application were observed. In the presence of BaCl(2), baclofen-evoked hyperpolarization with decreased resistance was observed. During application of baclofen, the firing rate of the action potentials by depolarizing step pulses was decreased. Application of baclofen reduced action potential duration evoked by a depolarization current pulse.These results indicated that activation of GABA(B) receptors inhibits the excitability of rat small diameter TRG neurons and this inhibitory action is mediated by potentiation of voltage-dependent K(+) currents. We therefore concluded that modification of nociceptive transmission in the trigeminal system by activation of GABA(B) receptors occurs at the level of small TRG neuron cell bodies and/or their primary afferent terminals, which are potential targets of analgesia by baclofen.

Animals↗