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ABSTRACT: Vagus nerve stimulation (VNS) is an approved antiepileptic and antidepressant treatment, which has recently shown promise as a therapy for drug-resistant primary headaches. Specific neurobiological mechanisms underlying its anticephalgic action are not elucidated, partly because of the deficiency of research-related findings. The spinal trigeminal nucleus (STN) plays a prominent role in pathophysiology of headaches by modulating pain transmission from intracranial structures to higher centers of the brain. To determine whether vagal stimulation may affect trigeminovascular nociception, we investigated the effects of VNS on the STN neuronal activity in the animal model of headache. In anesthetized rats the spike activity of the STN neurons with convergent orofacial and meningeal inputs was monitored, and the changes in neuronal responses to electrical stimulation of the dura mater under preconditioning or under continuous electrical stimulation of the left cervical vagus nerve were studied. Preconditioning vagal afferent stimulation (200-ms train of pulses at 30 Hz applied before each dural stimulus) did not produce substantial changes in the STN spike activity. However, continuous VNS with frequency of 10 Hz in 48% of cases significantly suppressed trigeminal neuronal responses to dural electrical stimulation. In line with the decrease in evoked activity, the VNS-induced depression of ongoing neuronal firing was observed. Although the inhibitory effect was prevailing, 29.5% of STN neurons were facilitated by VNS, whereas 22.5% were unresponsive to the stimulation. These results provide an evidence of VNS-induced modulation of trigeminovascular nociception, and therefore contribute to a deeper understanding of neurophysiological mechanisms underlying effects of vagal stimulation in chronic drug-resistant headaches.
Neuroscience 07/2012; 222:29-37. · 3.38 Impact Factor
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ABSTRACT: This review provides information on the role of serotonin and its receptors in the pathogenesis of primary headaches and,
particularly, migraine headaches. We summarized the data on the distinctive distribution of different 5-HT receptors in the
trigemino-vascular system and their involvement in the regulation of cerebral vascular tone, as well as in the modulation
of pain transmission in peripheral and central structures of the trigeminal complex. In addition, we discussed the pharmacodynamics
of several serotonergic drugs used in the treatment of migraine.
Keywordsserotonin–5-HT receptors–cerebral vasculature–trigeminal nerve–headache–migraine–triptans
Neurochemical Journal 04/2012; 5(2):92-99. · 0.29 Impact Factor
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ABSTRACT: Neurophysiological experiments on anesthetized rats were used to study the effects of various doses (12.5, 25, 37.5 mg/kg, i.v.) of drug composition migrepin (representing a combination of potassium-2,4-dichlorobenzoate, carbamazepine, and caffeine) on background firing of the trigeminal nucleus caudalis neurons and their responses to electrical stimulation of the dura mater. It was found that migrepin produces direct, dose-dependent inhibitory action on functional activity of TNC neurons. The results confirmed anti-migraine properties of the drug but did not exclude the necessity to study its action in clinical trials.
Eksperimental'naia i klinicheskaia farmakologiia 01/2011; 74(5):13-6.
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ABSTRACT: Neuroanatomical studies demonstrated the existence of direct descending projections from the insular cortex to the area of the solitary tract nucleus responsible for mediating the vagovagal reflexes of the proximal part of the gastrointestinal tract. These studies provided grounds for suggesting that one of the mechanisms mediating the influences of the insular cortex on stomach function may be modulation of its vagovagal reflex reactions, one of which is the antrofundal inhibitory reflex. Experiments on conscious dogs were performed to study the effects of electrical stimulation of the insular cortex on execution of the antrofundal gastric reflex in conditions of intermittent gastrointestinal tract activity during fasting. Stretching of the walls of the antral segment of the stomach during the active period of intermittent gastric activity led to suppression of contractions in the fundal segment. Electrical stimulation of the insular cortex was found to prolong this reflex reaction. Thus, one result of activation of the insular area of the cortex is enhancement of the inhibitory vagovagal gastric reflexes, in all probability occurring as a result of modulation of neurotransmission in the vagovagal reflex arc system.
Neuroscience and Behavioral Physiology 03/2010; 40(4):375-80.
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ABSTRACT: Experiments were performed on rats using retrograde axonal transport of horseradish peroxidase with the aim of identifying cells in the individual structures of the central nucleus of the amygdaloid body (CNAB) innervating the paraventricular nucleus of the hypothalamus. Labeled cells were seen in the ipsilateral CNAB throughout its rostrocaudal extent. The largest number of labeled neurons was seen in the middle third of the nucleus in the area corresponding to the intermediate subnucleus of the CNAB. Occasional cells were located in the medial and lateral subnuclei of the CNAB. Labeled neurons in the intermediate subnucleus were oval cells or cells of indeterminate shape.
Neuroscience and Behavioral Physiology 12/2009; 40(1):103-5.
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ABSTRACT: The locations and morphometric characteristics of efferent parasympathetic neurons in the dorsal motor nucleus of the vagus nerve and the cruciform parasympathetic nucleus of the spinal cord, innervating the area of the ileocecal sphincter and the ascending and transverse segments of the colon, were studied. Horseradish peroxidase solution was injected beneath the serous membranes of these parts of the intestine in urethane-anesthetized cats. After 48 h, animals were subjected to transcardiac perfusion with a fixative mixture and sections of the medulla oblongata and spinal cord were prepared and processed by the Mesulam method. The results showed that all these parts of the large intestine received parasympathetic innervation from neurons in the ventrolateral part of the dorsal motor nucleus, which were uniform in terms of their morphometric characteristics. The number of neurons of this group sending axons to the ileocecal area was greater than the number of neurons innervating the ascending colon. A second group of neurons, which were smaller cells, was located in the same part of the nucleus and innervated the transverse colon. The transverse colon also received innervation from neurons in the cruciform parasympathetic nucleus of the spinal cord.
Neuroscience and Behavioral Physiology 12/2008; 38(9):923-7.
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ABSTRACT: In acute experiments on urethane-anaesthetized cats, motor responses of different parts of the colon (the proximal and descending parts as well the rectum) to microstimulation of neurons of the sacral parasympathetic nucleus (SPN) were investigated. The stimulation was carried out by rectangle pulses of current with intensity 100-1000 microA, pulse width 0.5 ms and frequency 10 Hz. It was shown that the microstimulation of the SPN neurons located within SI-SIII segments of spinal cord induced mainly the excitatory motor responses of all regions of the colon. However the most pronounced responses were obtained when the neurons of SII segments were stimulated. On the whole, the responses of rectum to stimulation were greater than responses of the proximal part of the colon. Our results suggest that the SPN neurons located within SII segments play the most important role in reflex control of colon motility.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 11/2007; 93(10):1188-95.
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ABSTRACT: The localization and morphometric features of efferent parasympathetic neurons of the vagus dorsal motor nucleus and of the spinal sacral parasympathetic nucleus innervating the area of ileocaecal sphincter, ascending and transverse colon, were investigated. In urethane anaesthetized cats, the solution of horseradish peroxidase was injected under the serosa of the indicated areas of colon. In 48 hours animals were transcardially perfused with a fixative solution. Sections of the medulla oblongata and the sacral spinal cord were stained using Mezulam's technique (1978). It was shown that all the areas of the colon studied received parasympathetic innervation from the neurons of the ventrolateral part of the vagus dorsal motor nucleus, which were uniform according to their morphometric characteristics. The number of neurons in this group, sending their axons to the ileocaecal area, was greater than the number of neurons, innervating ascending colon. Second group of neurons, that was represented by smaller cells, was located in the same part of the nucleus and innervated transverse colon. Transverse colon had an additional parasympathetic supply from the neurons of the spinal sacral parasympathetic nucleus.
Morfologiia (Saint Petersburg, Russia) 02/2007; 132(6):34-8.
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ABSTRACT: The localization and morphological features of viscerosensory neurons of sacral spinal ganglia (SSG), innervating the colon, were investigated. In urethane anaesthetized cats, the solution of horseradish peroxidase was injected under the serosa of ascending and descending parts of the colon as well as of the rectum. After 48 hours animals were repeatedly anesthetized and transcardially perfused. Sections of SSG were stained according to Mezulam protocol (1978). All the regions of the colon studied were shown to receive afferent innervation from neurons of SSG SI, SII and SIII. Maximum number of the labeled cells was detected in SSG SII. The intensity of afferent innervation of the colon by the neurons of SSG was found to increase along its length in cranio-caudal direction.
Morfologiia (Saint Petersburg, Russia) 02/2006; 130(6):47-50.
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ABSTRACT: The pathogenesis of migraine is based on the aseptic inflammation of dura mater tissues surrounding the large cranial vessels, such as the superior sagittal sinus. This inflammation develops in conditions of antidromic activation of sensory terminals of the trigeminal nerve and is accompanied by changes in the responses of neurons in the spinal nucleus of the trigeminal nerve to electrical stimulation of the superior sagittal sinus. However, the characteristics of the responses of these neurons to this stimulation have received virtually no study. Experiments on anesthetized rats were performed with recording of the responses of 387 neurons in the spinal nucleus of the trigeminal nerve to electrical stimulation of the superior sagittal sinus. The results showed that the responses of neurons to this stimulation was biphasic, consisting of a short initial phase with a latent period of 7-19 (11.4 +/- 0.17) msec, followed by a longer-lived discharge with a latent period of 20-50 (34.2 +/- 0.8) msec. It is suggested that the first phase reflects orthodromic activation of perivascular A(delta) and C fibers of the trigeminal nerve, while the second phase is associated with activation of meningeal C fibers with low conduction velocities and/or secondary activation of the perivascular sensory endings of the trigeminal nerve by algogenic and vasoactive substances released from them during antidromic activation. These changes seen in animal experiments may serve as an indicator of the efficacy of antimigraine agents.
Neuroscience and Behavioral Physiology 07/2005; 35(5):555-9.
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ABSTRACT: Aseptic inflammation of tissues surrounding large meningeal blood vessels, e.g. the superior sagittal sinus, underlies pathogenesis of migraine. This inflammation develops due to antidromic activation of sensory trigeminal nerve endings and is followed by changes in responses of the spinal nucleus of the trigeminal nerve neurons to electrical stimulation of the superior sagittal sinus. However, characteristics of these reactions are still unclear. In experiments ou urethane-anesthetized rats, responses of 387 neurons of the spinal nucleus of the trigeminal nerve to electrical stimulation of the superior sagittal sinus, were recorded. It was tial discharge with the latency 7 to 19 ms (11.4 +/- 0.17 ms) and a subsequent long-lasting discharge with the latency 20 to 50 ms (34.2 +/- 0.8 ms). It is presumed that the first phase reflects orthodromic activation of prevascular A delta and C-fibers of the trigeminal nerve while the second phase is connected with activation of meningeal C-fibers which have low conduction velocity, and/or with a secondary activation of perivascular sensory endings of trigeminal nerve by releasing algogenic and vasoactive substances. These changes could be used as an indicator of efficacy of some antimigraine substances in animal experiments.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 02/2004; 90(1):3-10.
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ABSTRACT: In acute rat experiments the technique of retrograde axonal transport of horseradish peroxidase in the medial vestibular nucleus allowed to identify a group of neurones sending axons to the "stomach" region of a single tract nucleus. These neurones and, accordingly, the descending vestibular/solitary links can be viewed as the morphologic basis for vestibular influences on the gastric motor activity. As was shown, local irritation of the neurones initiates relaxation of the stomach wall. Activation of the anterior limbic cortex modulates the vestibular/autonomous responses of the intragastric pressure reduction. Irritation of the infralimbic cortex of the rat's brain may have a preventive effect on the stomach wall relaxation stimulated by the vestibular neurones projecting on the "stomach" region of single tract nucleus.
Aviakosmicheskaia i ekologicheskaia meditsina = Aerospace and environmental medicine 02/1999; 33(2):15-9.
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ABSTRACT: In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 05/1997; 83(4):33-44.
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ABSTRACT: Location peculiarities of insular neurones implicated in the regulation of gastrointestinal motility have been studied in acute experiments on rats. After microinjection of a horseradish peroxidase solution in a part of the dorsal vagal complex that receive gastric afferent inputs, retrogradely labelled cell bodies are observed in a certain area of the agranular and disgranular insular cortex. Electrical stimulation of the insular cortex area had no significant effect on heart and respiration rate but had evoked gastric tone changes. These results suggest that the insular cortex contains a specific cell group that provides direct output to the bulbar 'gastric' centre and takes part in regulation of gastrointestinal functions.
Neuroscience Letters 10/1996; 216(1):5-8. · 2.11 Impact Factor
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Doklady Akademii nauk / [Rossiĭskaia akademii nauk] 04/1996; 347(1):129-32.
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Doklady Akademii nauk / [Rossiĭskaia akademii nauk] 03/1995; 340(4):555-8.
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ABSTRACT: In acute experiments on cats, electrical stimulation of the anterior limbic cortex was shown to modulate activity of vagal input neurones of the nucleus of the tractus solitarius. In the majority of the solitary tract nucleus neurones the responses induced by electrical stimulation of the vagus were depressed by the stimulation of anterior limbic cortex. Under these conditions the patterns of responses or their latency were changed. Our results are discussed with respect to possible mechanisms for cortical control of sensory transmission in the nucleus of the tractus solitarius.
Neuroreport 10/1994; 5(14):1705-8. · 1.66 Impact Factor
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ABSTRACT: Mechanical stimulation of the cat stomach revealed two groups of neuronal responses in the solitary tract's nucleus: phasic and tonic those. The neurons with phasic responses were found mainly in the caudal portion of the nucleus and could be regarded as representing stomach's mechanoreceptors. The neurons with tonic excitatory and inhibitory responses were located diffusely in the nucleus. Possible significance of these groups of neurons for the gastric bulbar centre's activity, is discussed.
Fiziologicheskiĭ zhurnal SSSR imeni I. M. Sechenova 11/1991; 77(10):77-85.
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S S Panteleev
Fiziologicheskiĭ zhurnal SSSR imeni I. M. Sechenova 02/1990; 76(1):135-9.
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ABSTRACT: Electrical stimulation of the vagus' gastric branch evoked three types of responses in the solitary tract nucleus of anesthetized cats: phasic discharges, tonic excitation and tonic inhibition. The majority of neurons with phasic and tonic inhibitory types of the responses were found in caudal part of the nucleus. The neurons whose spontaneous activity was increased during repetitive stimulation, were located in the rostral part of the nucleus.
Fiziologicheskiĭ zhurnal SSSR imeni I. M. Sechenova 10/1989; 75(9):1220-9.
