The present study was designed to examine whether together with analgin, microinjection of another type of NSAIDs clodifen, ketorolac and xefocam into the PAG and the nucleus raphe magnus (NRM) leads to the development of tolerance in male rats. 
We hypothesized that descending inhibitory pathways mediate the DNIC mechanism and that the neural network of the DNIC loop exists in the middle brainstem, likely in a more rostral part than formerly assumed, possibly the nucleus raphe magnus (RMg).
In this study, we investigated the mechanisms underlying synaptic and behavioral actions of chronic morphine-induced DORs and their interaction with MORs in nucleus raphe magnus (NRM) neurons important for opioid analgesia.
To determine sex and regional differences in the properties of serotonin (5-HT) neurons of the raphe nuclei, the responsiveness to parachlorophenylalanine (PCPA) of 5-HT neurons in the dorsal and median raphe nuclei (DR and MR) and the nucleus raphe magnus (RMg) was analyzed by counting 5-HT-immunoreactive (5-HT-ir) cells.
Serotonin-immunoreactive cells of the raphe obscurus and raphe magnus, parapyramidal cells of the B3 region, subependymal cells of the ventral parapyramidal region, and cells of the ventrolateral periaqueductal gray region were activated by hypotensive hemorrhage, but not by hypotension alone.
In contrast, P3 HI did not alter counts in the dorsal raphe interfascicular and raphe magnus nuclei.
MAC was decreased 9% after mid-medullary transections that were placed caudal to the nucleus raphe magnus but rostral to the dorsal reticular nucleus; however, only weak, single movements occurred.
The aim of the present work was to further provide evidence for the supraspinal mechanisms of action for N/OFQ-mediated nociceptive facilitation by examining the effect of N/OFQ in the vlPAG on neurotransmitter release in the descending pain-control system, including the nucleus raphe magnus (NRM), nucleus reticularis gigantocellularis (NGC) and dorsal horn of the spinal cord.
Local blockade of neuronal activity by bilateral microinjections of fluorescent muscimol (a GABA(A) receptor agonist tagged with a fluorophore that allowed visualization of the injections) into both the LPGi and the raphe magnus nucleus prevented the inhibitory effect of noxious stimuli > or = 48 degrees C on the cardiac baroreflex.
Immunohistochemical double-labeling technique with Fos and markers for noradrenergic and serotonergic neurons was used to examine if an intraplantar formalin injection (an acute noxious input) changed the effect of morphine on noradrenergic neurons of the A7 and A5 cell groups, and serotonergic neurons of the nucleus raphe magnus (NRM).
Muscimol inactivation of the medullary raphe magnus blocked the analgesia normally observed during water ingestion, showing the involvement of brainstem endogenous pain inhibitory mechanisms in ingestion analgesia.
In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons..
The induction of retching was suppressed by weak stimulation (20microA, 20Hz, 0.5ms duration) of the pontine area corresponding to the nucleus raphe magnus (NRM).
SB 242084 did not significantly alter the c-Fos response in the arcuate nucleus or the raphe magnus nucleus. These data indicate that 2C receptor signaling activates a diffuse neural network, presumably mediating anorexia and other responses to LPS; they also suggest that the arcuate and the raphe magnus neurons that express c-Fos after LPS are not necessary for LPS anorexia..
In previous paper, we reported that stimulation of the nucleus raphe magnus (stim-NRM) inhibits the induction of retching by afferent vagal fibers (VAs).
The raphe magnus (RM) participates in opioid analgesia and contains pain-modulatory neurons with respiration-related discharge.
The analgesia associated with eating is dependent on activity in the medullary raphe magnus, the final common brain stem region in endogenous analgesia pathways. Since raphe magnus modulates processing of innocuous as well as nociceptive information, the sensory suppression accompanying eating is likely a more general depression of the response to external stimulation.
Colocalization of the classic neurotransmitters serotonin (5-HT) and gamma-aminobutyric acid (GABA) (or the enzyme that synthesizes the latter, glutamate decarboxylase) has been reported in a few neurons of the rat raphe magnus-obscurus nuclei.
Arginine vasopressin (AVP) in the nucleus raphe magnus (NRM) has been implicated in antinociception.
It is released there mainly by descending axons of the medulla's nucleus raphe magnus (NRM).
Our previous study has pointed that pain stimulation induced AVP increase in the nucleus raphe magnus (NRM), which plays a role in pain modulation.
Between-condition paired t-tests (cognitive task>rest) demonstrated modulation within this network localized to the dorsal anterior cingulate and pontine raphe magnus nucleus.
Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG).
We show that diverse brainstem regions differentially target the 5HT neurons of the dorsal raphe (DR) and the nucleus raphe magnus of the rostroventral medulla (RVM).
Here we investigated a differential role of the raphe magnus (RMg), pallidus (RPa) and the obscurus (ROb) nuclei in the neural control of DIA and GH muscle activity in rats under volatile anesthesia.
BACKGROUND: The nucleus raphe magnus (NRM) is involved in thermoregulatory processing.
36) decreased AVP concentration in the hypothalamic paraventricular nucleus (PVN), and increased AVP concentration in the hypothalamic supraoptic nucleus (SON), periaqueductial gray (PAG), caudate nucleus (CdN) and raphe magnus nucleus (RMN), but did not change AVP concentration in the pituitary, spinal cord and plasma.
Improgan, a cimetidine derivative which lacks activity at known histamine, opioid or cannabinoid receptors, acts by an unknown mechanism in the periaqueductal gray (PAG) and raphe magnus (RM) to stimulate descending, analgesic circuits.
RESULTS: 1) After injection of PRV, PRV-IR positive cells widely distributed in the spinal cord (cervical, thoracic and lumbar segments), brain stem (nucleus of solitary tract, cuneate nucleus, gigantocellular reticular nucleus, nucleus of spinal tract of trigeminal nerve, nucleus raphe magnus, locus caeruleus, etc), hypothalamus and cerebral cortex in each group.
By contrast, TPH-immunoreactivity was restricted to a relatively small subset of RVM neurons concentrated in the nucleus raphe magnus and pallidus, as expected.
In this review we focus on 2 of them, the periaqueductal gray matter and nucleus raphe magnus.
0.5%), raphe magnus and pallidus (1.1% vs.
LR animals did not however yield any significant difference in mu opioid receptor mRNA levels in locus coeruleus (LC), ventral periaqueductal gray (vPAG), nucleus raphe magnus (NRM) and nucleus reticularis paragigantocellularis (NRPG) between these two groups of animals.
The midline medulla oblongata, which includes the nucleus raphe obscurus, raphe magnus and raphe pallidus (NRP), is involved in regulation of cardiovascular responses.
Many brain nuclei composing a complicated network are involved in processing acupuncture analgesia, including the nucleus raphe magnus (NRM), periaqueductal grey (PAG), locus coeruleus, arcuate nucleus (Arc), preoptic area, nucleus submedius, habenular nucleus, accumbens nucleus, caudate nucleus, septal area, amygdale, etc.
There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM).
We tested the idea that migraine triggers cause cortical activation, which disinhibits craniovascular sensation through the nucleus raphe magnus (NRM) and thus produces the headache of migraine.
The expression of the 5-HT2A receptor mRNA in the nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and spinal dorsal horn of mono-arthritic rats after a ten-day treatment with tramadol was measured with in situ hybridization.
AIM: In the present study, we assessed the role of 5-hydroxytryptamine (5-HT) receptors (5-HT(1A), 5-HT(2) and 5-HT(7)) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia.
Further, EA activated serotonin- and catecholamine-containing neurons in the nucleus raphe magnus and locus coeruleus that project to the spinal cord.
Under conditions that produce physiological responses typical of the defense reaction, electrical stimulation of the dorsal periaqueductal gray (dPAG) was found to double c-Fos immunoreactive serotonergic neurons within the mid-rostrocaudal extent of the B3 group (which comprises the raphe magnus and the lateral paragigantocellular reticular nuclei) in anesthetized rats.
The three brainstem regions examined included the mid-brain periaqueductal gray (PAG), the medullary nucleus raphe magnus (NRM), and the spinal trigeminal nucleus (STN).
Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia.
In rats, opioids produce analgesia in large part by their effects on two cell populations in the medullary raphe magnus (RM).
Ectopic expression of TH was observed in the raphe magnus nucleus, where serotonergic neural cell bodies are located.
In addition, GBP-induced increase in c-Fos expression was observed in the dorsal raphe (DRN) and in the nucleus raphe magnus.
Serotonergic neurons represent the major cell type (comprising 15-20% of the neurons) in raphe magnus nucleus (RMg), which is a medullary raphe nucleus.
Male Sprague-Dawley rats were implanted with intracerebral guide cannulae into the nucleus raphe magnus (NRM) or the nucleus gigantocellularis (Gi).
They discharge tonically at a rate modulated by the sleep-wake cycle and, in the case of medullary serotonergic cells in raphe magnus and the adjacent reticular formation (RM), are excited by cold challenge.
36) reduced oxytocin concentration in the hypothalamic supraoptic nucleus, and elevated oxytocin concentration in the hypothalamic suprachiasmatic nucleus, hypothalamic ventromedial nucleus, thalamic ventral nucleus, periaqueductal gray, raphe magnus nucleus, caudate nucleus, thoracic spinal cord and lumbar spinal cord, but did not alter oxytocin concentration in the hypothalamic paraventricular nucleus, anterior pituitary, posterior pituitary and plasma.
One of the possible sites of action of the analgesic effect of morphine is the Nucleus raphe magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus raphe magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus raphe magnus of the rat. These results suggest that the Nucleus raphe magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions..
In particular, the paper discusses the impact of sciatic nerve ligature on genomic and biochemical components of neurosteroidogenesis in the spinal cord and brainstem areas including the parabrachial, raphe magnus and dorsal raphe nuclei which control nociception.
A significant (p<0.05) reduction was observed in the nucleus raphe magnus, medial caudate, ventral thalamus, amygdala, ventral tegmental area, medial forebrain bundle, nucleus accumbens, medial anterior olfactory nucleus and superior olive. However, there were some terminal regions (e.g., accumbens, anterior olfactory, lateral thalamus, raphe magnus and obscurus) in which the chronic flesinoxan treatment resulted in a significant reduction of synthesis, suggesting that there was not a full desensitization across the brain of the receptors controlling 5-HT synthesis..
LCGU was decreased in a number of limbic (nucleus accumbens and ventral pallidum) and cortical (medial/ventral orbital and infralimbic) regions and in the raphe magnus nucleus in quinpirole-sensitized rats (P<0.05 vs. Quinpirole-sensitized rats pretreated with clorgyline had similar alterations in LCGU, but LCGU was higher in the locus coeruleus compared to quinpirole alone (P<0.05), was not decreased in the raphe magnus nucleus, and was decreased in the piriform cortex and septum.
Pain stimulation induced oxytocin concentration decrease in the hypothalamic supraoptic nucleus, and increase in the locus coeruleus, raphe magnus nucleus, caudate nucleus and spinal cord, but no change in the hypothalamic paraventricular nucleus and plasma.
Previous results from our laboratory have demonstrated that nucleus raphe magnus (NRM) is also a structure involved in the modulation of TI behavior, as chemical stimulation through carbachol decreases the duration of TI in guinea pigs.
Neurons in the CnF project to medullary nucleus raphe magnus (NRM), which plays an important role on pain modulation.
Stimulation of the rostral raphe magnus/pallidus elicited a reduction in SkBF without affecting sweat secretion. Stimulation of the mid to caudal raphe magnus/pallidus elicited an increase in both sweat secretion and SkBF. The raphe magnus/pallidus may play a crucial role in skin vasomotor and sudomotor responses in the cat footpad..
Phospho-p38 MAPK-immunoreactive (p-p38 MAPK-IR) neurons were observed in the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (GiA).
Just over half of them are found at the pontomedullary junction within raphe obscurus, raphe magnus, and gigantocellular nucleus pars alpha.
We observed that an intravenous (i.v.) injection of (+)-bicuculline, a GABA(A) receptor antagonist, significantly reduced respiratory inhibition induced by electrical stimulation of the raphe magnus (RM) or the raphe obscurus (RO).
However, persistent TMJ inflammation significantly increased Fos-LI neurons in the nucleus raphe magnus (NRM) induced by subsequent formalin injection of the masseter muscle and hindpaw (70.2% increase and 53.8% increase, respectively, over the control TMJ-saline-injected rats; P < 0.05).
Microinjection of muscimol, a GABA(A) receptor agonist, into raphe magnus (RM) reduced CRD-evoked suppression of withdrawals, evidence that RM neurons contribute to this heterotopic antinociception.
We found that conditioning stimulation of cutaneous nerves (sural, superficial peroneus and saphenous) and of the nucleus raphe magnus often inhibited, in a differential manner, the early and late components of the intraspinal focal potentials produced by stimulation of low and high threshold myelinated PAN afferents, respectively.
The monoamine neurotransmitter serotonin is released from spinal terminals of nucleus raphe magnus (NRM) neurons and important in sensory and motor control, but its pattern of release has remained unclear.
Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex.
We found that microinjection of ATP (0.1-0.2 M, 10-70 nl) into raphe magnus (RM) caused dose-dependent decreases in integrated phrenic amplitude and respiratory frequency, whereas injection of ATP into raphe pallidus (RP) caused dose-dependent increases in phrenic amplitude and respiratory frequency.
The following results were obtained: (1) At PND 3, numerous CTb-labeled neurons (CTLN) were already present in the raphe pallidus (B1), while few CTLN were seen in raphe obscurus (B2) and raphe magnus (B3).
Finally, the gigantocellularis complex (nucleus reticularis gigantocellularis/paragigantocellularis), nucleus raphe magnus and nucleus raphe pallidus also projected to the caudal divisions of the STN.
The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat.
The nucleus raphe magnus (NRM) is related to the modulation of nociceptive and behavioral responses.
In the nucleus raphe magnus (NRM), a critical brainstem site for opioid analgesia, the GABA(A) receptor-mediated inhibitory postsynaptic current (IPSC) was significantly increased in NRM neurons kept in a morphine-tolerant state from chronic morphine-treated rats.
There is a system for pain control at an encephalic and spinal level, principally made up of the periaqueductal grey matter, the periventricular area, the nucleus raphe magnus, and the pain-inhibition complex situated in the posterior horns of the spinal cord.
To test whether medullary OFF cells modulate BAT activity, the mu-opiate receptor agonist (d-Ala2, N-Me-Phe4, Gly-ol5)-enkephalin (DAMGO) was microinjected into the raphe magnus, a manipulation that selectively activates OFF cells.
Train pulse stimuli (100 Hz, 10-30 microA) were applied in the regions of the caudal raphe nuclei: the raphe magnus (RM), raphe pallidus (RP) and raphe obscurus (RO).
In the periaqueductal gray matter and in the nucleus raphe magnus, naratriptan selectively activates inhibitory neurons which project to the trigeminal nucleus and spinal cord and which exert inhibitory influences on trigeminovascular sensory input.
Our neuroanatomical findings indicate a direct neural pathway connecting the dorsal midbrain and monoaminergic nuclei of the descending pain inhibitory system, with profuse synaptic terminals mainly in the pontine reticular formation, gigantocellularis nucleus, and nucleus raphe magnus. The midbrain tectum-gigantocellularis complex and midbrain tectum-nucleus raphe magnus neural pathways may provide an alternative output allowing the organization of the fear-induced anti-nociception by mesencephalic networks..
Phospho-extracellular signal-regulated kinase-immunoreactive (p-ERK-IR) neurons were observed in the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (GiA).
However, in the upper medulla oblongata alpha2 mRNA was expressed in several large neurons of the gigantocellular reticular nucleus and the raphe magnus nucleus of mice, but not of rats.
Academic Press, San Diego], especially with respect to the size and/or location of the catecholaminergic retrorubral field (A8 group), A5, A1, and C1 cell groups, and the serotonergic B4 group, reticulotegmental nucleus (B9 group), lateral paragigantocellular nucleus and raphe magnus nucleus (B3 group).
This is mediated by endogenous opioidergic circuits located in the PAG itself, in the nucleus raphe magnus and adjacent structures, and in the spinal cord. This effect was abolished by microinjection of naloxone (0.5 microg/0.5 microl) into the ventrolateral and lateral PAG or into the nucleus raphe magnus or by direct application of naloxone (50 microg/50 microl) onto the spinal cord surface above the recorded neuron.
The structures examined for fos were the trigeminal nucleus, infratrigeminal nucleus, reticular nuclei, nucleus raphe magnus, pontine blink premotor area, and superior salivatory nucleus. After PAG with SSS stimulation, on the side ipsilateral to the site of PAG stimulation, fos was significantly greater in the nucleus raphe magnus.
These projections were established early in development and likely originated from the dorsal raphe, median raphe, raphe pontis, raphe magnus, and reticularis pontis oralis.
Sucrose also elicited Fos expression in several brainstem areas associated with centrally mediated analgesia, including the periaqueductal gray and the nucleus raphe magnus. Intraoral sucrose activates neurons in the periaqueductal gray and nucleus raphe magnus, two key brainstem sites critically involved in descending pain modulation..
There are ORL(1) mRNA expression in the nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) of rat mesencephalon.
In this study, we demonstrate that withdrawal from chronic morphine significantly upregulates the mRNA level of adenylyl cyclase (AC) VI and VIII isoforms and immunoreactivity of ACV/VI in the nucleus raphe magnus (NRM), a brainstem site critically involved in opioid modulation of pain.
Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia.
nNOS Neurons were localized in several nuclei throughout the brainstem; the dorsolateral periaqueductal gray, pedunculopontine tegmental nucleus, dorsal raphe nucleus, laterodorsal tegmental nucleus, lateral parabrachial nucleus, rostral ventrolateral medulla, nucleus tractus solitarius and raphe magnus.
Localization of Tag in P0-P90 animals becomes restricted to a single compact cellular mass in mesencephalon at the level of the dorsal raphe, raphe magnus and lateral paragigantocellular nuclei.
Although premotor neurons controlling other effector organs than the cardiovascular system have been largely unknown, recent accumulating findings have suggested that medullary raphe regions including the raphe pallidus and raphe magnus nuclei are candidates for the pools of excitatory sympathetic premotor neurons involved in thermoregulation.
The periaqueductal gray matter (PAG) and the nucleus raphe magnus and adjacent structures of the rostral ventromedial medulla (RVM), with their projections to the spinal dorsal horn, constitute the "efferent channel" of a pain-control system that "descends" from the brain onto the spinal cord.
EPIB injection (0.04 nmol/rat) into the nucleus raphe magnus significantly decreased C-fiber EMG activity by 67%, suggesting a supraspinal site of action.
The phospho-ERK-immunoreactive (p-ERK-IR) neurons were observed in the nucleus raphe magnus (NRM), nucleus reticularis gigantocellularis pars alpha (GiA) and LC.
This data is similar to the influence of two pontine structures of mammals, the locus coeruleus and the nucleus raphe magnus.
This action of NSAIDs engages endogenous opioids at the PAG, the nucleus raphe magnus and the spinal cord.
In response to hemorrhage, double-labeled Fos/5-HT neurons were located in the B3 region which includes the raphe magnus (RM) and its lateral extension.
Intraperitoneal administration of MK-801 (0.03, 0.3 and 3.0 mg/kg) prior to the onset of experimental tooth movement reduced c-Fos in the TSNC (Vc I/II, Vodm and Vor) but increased it in the nucleus raphe magnus (NRM), ventrolateral PAG (vl PAG), DR and EW.
The analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) is due to their action upon the peripheral damaged tissues, the spinal cord, and brain stem structures of the 'descending pain-control system' such as the periaqueductal gray matter (PAG) and the nucleus raphe magnus (NRM).
Nucleus raphe magnus (NRM) is one of the cellular groups of the brainstem that is involved in the physiologic responses to hypoxia and contains nitric oxide (NO) synthase.
Previous studies have shown that both OFQ immunoreactivity and preproorphanin FQ (ppOFQ) mRNA expression could be observed in the brain regions involved in pain modulation, e.g., nucleus of raphe magnus (NRM), dorsal raphe nucleus (DRN), and ventrolateral periaqueductal gray (vlPAG).
Neurons expressing vesicular glutamate transporter 3 (VGLUT3) were distributed in the rat medullary raphe regions, including the raphe magnus and rostral raphe pallidus nuclei, and mostly lacked serotonin immunoreactivity.
Neurons in raphe magnus (RM) and the adjacent nucleus reticularis magnocellularis (NRMC) respond to visceral stimuli and can facilitate the behavioral reaction to visceral stimulation.
There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA.
Stimulation of cutaneous nerves (sural and superficial peroneus) with single pulses and of the posterior articular nerve, the ipsilateral reticular formation, nucleus raphe magnus and contralateral motor cortex with trains of pulses often had qualitatively different effects.
Acute toluene administration in rats induced a significant increase in the numbers of neural cells immunostained for p75NTR in several brainstem regions, such as the raphe magnus and the nucleus of the solitary tract, as well as in the lateral reticular, gigantocellular, vestibular and ventral cochlear nuclei, without any in the facial and spinal trigeminal nuclei and the dorsal horn of the spinal cord.
There is much evidence to indicate that the active site of morphine for inducing effective analgesia is in the raphe magnus nucleus, where serotonin (5-HT, 5-hydroxytryptamine) acts as a primary transmitter. Therefore, we developed the hypothesis that 5-HT released in the raphe magnus nucleus could be related to the effectiveness of morphine in two mice models of neuropathic pain, diabetic (DM)-induced neuropathy and sciatic nerve ligation (SL). These results suggest that the decrease in 5-HT levels in the raphe magnus nucleus may be related to attenuation of the analgesic effect of morphine caused by the abnormal pain state found in diabetes and partial peripheral nerve injury..
Although the importance of the nucleus raphe magnus in descending inhibitory control of nociception is clear, it is not known whether these effects are equivalent for different types of nociception. Thus, we examined the differential inhibition of behavioral responses evoked by A delta or C fiber thermonociceptor activation by electrical stimulation of nucleus raphe magnus neurons as well as the involvement of different classes of opiate receptors in this inhibition. In general, it was necessary to apply twice as much current to the nucleus raphe magnus to produce criterion antinociception for A delta mediated versus C fiber mediated nociceptive responses. Intrathecal administration of the nonselective opioid receptor antagonist, naltrexone, or the delta(1) opioid receptor antagonist, naltrindole, attenuated both A delta and C fiber antinociception induced by nucleus raphe magnus stimulation with similar efficacy. In contrast, intrathecal administration of naloxonazine, a micro specific opioid receptor antagonist, or naltriben, a delta(2) specific opioid receptor antagonist, preferentially attenuated nucleus raphe magnus induced antinociception for C fiber responses when compared with A delta mediated responses. These findings suggest that nociception evoked by the activation of A delta or C fiber nociceptors is under pharmacologically distinguishable descending control from the nucleus raphe magnus.
By contrast, in the caudal pons and medulla oblongata, neurons within the caudal raphe complex (raphe magnus, raphe obscurus, raphe pallidus nuclei and parts of the adjacent lateral reticular formation) project to the brainstem nuclei and to the spinal cord.
In contrast, levels of dynorphin(1-17) in the nucleus raphe magnus, nucleus reticularis gigantocellularis pars alpha, parabrachial nuclei, microcellular tegmentum, pontine periaqueductal gray, and midbrain periaqueductal gray were not affected at any time after injection of complete Freund adjuvant.
ambiguus, rostroventrolateral n., C3 adrenaline cell group, raphe obscurus n., raphe pallidus n., raphe magnus n., lateral paragigantocellular reticular n., locus coeruleus, subcoeruleus n., Kolliker-Fuse n., A5 cell group, central gray matter, paraventricular hypothalamic n.
The present study was undertaken to investigate the role of oxytocin in antinociception in the nucleus raphe magnus (NRM) of rats and the possible interaction between oxytocin and the opioid systems.
Blockade of neuronal function in raphe magnus/pallidus and the parapyramidal region in anesthetized rabbits prevents cutaneous vasoconstriction elicited by painful stimuli.
A 38-year-old woman is described with symptomatic strictly right-sided migraine associated with a pontine cavernoma affecting the contralateral (left) nucleus raphe magnus.
In this study, both recordings in vitro and behavioral analyses in vivo were used to examine cellular and behavioral actions mediated by alpha1- and alpha2-adrenoceptors on neurons in the nucleus raphe magnus.
Pre-microinjection of lidocaine (4%) into the nucleus raphe magnus (NRM) (0.5 microl), ipsilateral nucleus reticularis gigantocellularis (NGC) (0.6 microl), or nucleus gigantocellularis pars alpha (NGCalpha) and nucleus reticularis paragigantocellularis lateralis (NPGL) (0.5 microl) markedly reduced intra-vlPAG microinjection of OFQ-induced facilitatory effects on nociceptive responses of WDR neurons.
In the nucleus raphe magnus (NRM), a brainstem structure that controls spinal pain transmission, we found that kappa-receptor agonists presynaptically inhibited glutamate synaptic currents in both of the two cell types that are thought to respectively inhibit or facilitate spinal pain transmission.
In contrast to the acute treatment, a 7-day administration increased 5-HT synthesis rates in the dorsal raphe (24%), but decreased it in raphe magnus (35%), superior olive (45%), caudate (31%), superior (38%) and inferior (53%) colliculus, and in the auditory cortex (35%).
After unilateral iontophoretic injections of Fluoro-Gold into the vestibular nuclei, retrogradely labeled neurons were found in the dorsal raphe nucleus (including the dorsomedial, ventromedial and lateral subdivisions) and nucleus raphe obscurus, and to a minor extent in nucleus raphe pallidus and nucleus raphe magnus.
In the brainstem, retrograde labeling occurred at the periaqueductal gray, red nucleus, parabrachial area, nucleus raphe magnus, nucleus tractus solitarii, lateral reticular nucleus and dorsal and ventral medullary reticular formation.
The nucleus raphe magnus (NRM) is one of the brainstem cell groups involved in physiological responses to hypoxia.
Discrete injection of the tracer Cholera toxin, subunit B, (ChB) was centred in the rat SCN, and a few retrograde labelled neurones were distributed in the dorsal and median raphe nuclei (MnR) and in the rostral part of the raphe magnus (RMg), but no neurones were found in the raphe pallidus or raphe obscurus.
Morphine treatment for 7 days resulted in the development of tolerance to morphine's analgesic effect and produced a significant decrease in the steady-state NR1 mRNA levels in the spinal cord dorsal horn (by 16%), and an elevation in nucleus raphe magnus and medial thalamus (by 26 and 38%, respectively).
The medullary command nucleus is comprised of neurons located within the nucleus raphe magnus, and forms a descending spinal pathway to the EMNs..
The largest number of such neurons was located in the rostral ventromedial medulla within the ventral gigantocellular nucleus, gigantocellular nucleus pars alpha, raphe obscurus, and raphe magnus.
The alpha4-subunit immunoreactivity was enriched in serotonergic (nucleus raphe magnus, pallidus, obscurus, and dorsalis) and noradrenergic (A5, locus coeruleus (LC), A7) areas associated with antinociception, where it was commonly colocalized with serotonin (5-HT) or tyrosine hydroxylase (TH) immunoreactivity. Epibatidine produced a robust (2-5-fold) increase in c-Fos expression, which was not dose dependent, in all of these areas examined except the nucleus raphe magnus.
Most conspicuous among the latter were structures implicated in the descending control of nociceptive inputs (e.g., the periaqueductal gray, dorsal raphe, gigantocellular reticular nucleus, pars alpha, lateral paragigantocellular, and raphe magnus), in keeping with the postulated role of NTS2 receptors in the mediation of neurotensin's supraspinal antinociceptive actions.
In 15 and 21 days old male and female rats, 5-HT(7) receptor immunoreactive dots were most clearly detected in MPA, hypothalamus, raphe pallidus, raphe magnus and brainstem reticular formation.
This study examined the role of spinal GABAergic, serotoninergic and alpha(2) adrenergic receptors in the antinociception produced by the microinjection of equi-antinociceptive doses of selective opioid receptor agonists in the nucleus raphe magnus (NRM) or the nucleus reticularis gigantocellularis pars alpha (NGCpalpha) of the rat.
The present study demonstrates that activation of kappa-opioid receptors enhances Ih by increasing its maximum current in brainstem neurons in the nucleus raphe magnus.
RESULTS: Chronic ethanol treatment, as delivered in the present experiment, induced a significant increase in the rate of 5-HT synthesis in descending serotonergic cell bodies (raphe pallidum, raphe obscurus, raphe magnus), nigrostriatal structures, the hippocampus and cortices.
Medullary raphe magnus (RM) on and off cells are thought to modulate spinal nociception by gating withdrawals evoked by noxious stimulation.
Different reactions occur in response to acute pain stimulation across behavioral states; pain reactions are modulated by the activity of serotonergic and non-serotonergic cells in the raphe magnus (RM).
Physiological studies of neurons in raphe magnus (RM) and the adjacent nucleus reticularis magnocellularis (NRMC) have demonstrated that the response to noxious cutaneous stimulation predicts the response to opioid administration and therefore a cell's functional role in nociceptive modulation.
raphe magnus, obscurus, and pallidus) send dense projections into the spinal cord, especially to the dorsal horn, intermediolateral column, and ventral horn. raphe magnus), autonomic activity (n.
We have used double-label in situ hybridization techniques to examine the cellular localization of GABAB receptor mRNA in relation to serotonin transporter mRNA and glutamic acid decarboxylase mRNA in the rat dorsal raphe, median raphe and raphe magnus nuclei.
Intrathecal application of 5-HT or electrical stimulation or glutamate microinjection into the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis(NGC) may produce inhibition and/or facilitation of spinal nociceptive transmission.
This property proved to be important for the co-detection of reporter proteins with neuronal mRNAs, readily detected at early but not at late stage of infection, as shown in tyrosine-hydroxylase expressing A5 catecholaminergic neurons and in serotonin transporter expressing raphe magnus neurons..
The caudal cluster consisted of three divisions: the raphe obscurus nucleus, the raphe pallidus nucleus and the raphe magnus nucleus. raphe magnus was associated with the midline of the medulla and was found rostral to both the raphe obscurus and raphe pallidus.
AIM: To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats.
Pseudorabies virus-infected neurons in the ventrolateral medulla were present in the nucleus paragigantocellularis, reticular formation of the medulla, raphe pallidus and raphe magnus.
The present study was designed to investigate the expression of 5-hydroxytryptamine (5-HT) (2A) receptor mRNA in the nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) in a monoarthritic rat model using an in situ hybridization technique.
The brainstem materials were collected and studied in an attempt to elucidate the relationship between sleep apnea, and prone sleep position and gliosis in some nuclei associated with cardiorespiratory characteristics, such as nucleus ambiguus in the medulla oblongata and the solitary nucleus, as well as structures associated with arousal phenomenon, such as the reticular formation, the superior central nucleus and the nucleus raphe magnus in the pons, the dorsal raphe nuclei in the midbrain and medulla oblongata, periaqueductal gray matter in midbrain, and locus ceruleus.
Electrostimulation of the central gray matter in the sylvian aqueduct and nucleus raphe magnus produced an antiarrhythmic effect during acute myocardial ischemia. Destruction of the central gray matter in the sylvian aqueduct and nucleus raphe magnus decreased electrical stability of ischemic myocardium..
Major sources of serotonergic input to the RVLM were shown to include the raphe obscurus, raphe pallidus and raphe magnus with a minor contribution from the ventrolateral, lateral and ventral regions of the periaqueductal gray matter, and the dorsal raphe nucleus.
Electrical stimulation (ES, 0.1 ms, 100 Hz, 20-200 A) was delivered to the rostral ventromedial medulla (RVM), mainly the nucleus raphe magnus (NRM).
Details concerning the pathways from the spinal trigeminal, nucleus tractus solitarius, raphe magnus, raphe pallidus, and the rostral and caudal linear raphe nuclei to subsets of midline and intralaminar thalamic sites are discussed in the text.
Regrowth of brainstem raphe axons across the transplant site was shown by the presence of serotonergic axons in the spinal cord caudal to the transection site, and by retrograde labelling of cells in the nucleus raphe magnus after injections of fluorogold into the caudal spinal cord.
A few double-labeled neurons were also observed in nucleus raphe obscurus and nucleus raphe magnus.
In rabbits, raphe magnus/pallidus neurons form a link in the CNS pathway regulating changes in cutaneous blood flow elicited by nociceptive stimulation and activation of the central nucleus of the amygdala.
AIM: Examine the expression of 5-HT2A receptor mRNA and co-localization of 5-HT2A receptor mRNA with 5-HT immunoreactivity in nucleus raphe magnus (NRM) neurons following carrageenan inflammation.
At this survival time several brain stem nuclei including the A5 noradrenergic cell group, the caudal raphe nuclei (raphe obscurus, raphe pallidus, raphe magnus), the A1/C1 noradrenergic and adrenergic cell group, the nucleus of the solitary tract, the area postrema, the gigantocellular reticular nucleus, and the locus coeruleus contained virus-infected neurons.
The number and proportion of neurons according to their type and size in the raphe magnus Nucleus stained by the Golgi-Cox and Nissl methods were compared in male and female infants.
Anatomical studies have shown a strong projection from the medial preoptic nucleus of the hypothalamus (MPO) to both the periaqueductal gray (PAG) and nucleus raphe magnus (NRM).
Serotonergic cells in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis (NRMC) project to the spinal cord where they are likely to modulate nociceptive transmission.
RESULTS: We observed in the fibers and/or the cell bodies located in the dorsal raphe nucleus a total of 14 neuropeptides, 12 in the raphe pallidus, 11 in the medial raphe, 10 in the raphe magnus, 8 in the raphe pontis and 7 in the raphe obscurus. We observed immunoreactive cell bodies in the raphe pallidus (with neurokinin A/leucine enkephalin), in the medial raphe (beta endorphin/alpha neo endorphin), in the raphe magnus (leucine enkephalin) and in the dorsal raphe (beta endorphin/alpha neo endorphin/methionine enkephalin Arg6 Gly7 Leu8/leucine enkephalin/neurokinin A/neurotensin).
In urethane-anesthetized rats with body temperature maintained at 39-40 degrees C, electrical stimulation of raphe magnus/pallidus/parapyramidal region within 0.5 mm of the ventral medullary surface reduced arterial blood flow to the tail cutaneous bed (measured with a chronically implanted Doppler ultrasonic flowmeter) from 28+/-5 to 6+/-1 cm/s (P<0.01), without changing mesenteric arterial blood flow, and with only small, variable changes in arterial pressure. Our findings add to evidence that raphe magnus/pallidus/parapyramidal neurons are involved in regulating cutaneous blood flow in response to changes in body temperature in the rat..
In the brain, commonly labeled neurons were found in the Al noradrenalin cells/Cl adrenalin cells/caudoventrolateral reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse nucleus, A5 cell group, central gray matter, paraventricular hypothalamic nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed nucleus of stria terminalis and amygdaloid nucleus.
The raphe magnus is part of an interrelated region of medullary raphe and ventromedial reticular nuclei that project to all areas of the spinal gray.
Whether progesterone (P(4)) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) have anti-seizure effects through actions in the raphe magnus (NRM) was investigated.
Immunoreactive cell bodies were not seen in the nucleus raphe magnus (NRM) or PAG.
In the acute treatment studies, WAY100635 (1 mg/kg) induced a significant increase in 5-HT synthesis in the median raphe nucleus and some nerve terminal structures (range between 18 and 53%), while WAY100135 (10 mg/kg) produced a significant decrease of synthesis, in the range between 16 and 33%, in the raphe magnus nucleus and several projection areas.
To understand the cellular and molecular mechanisms by which neurotensin (NT) induces an analgesic effect in the nucleus raphe magnus (NRM), whole-cell patch-clamp recordings were performed to investigate the electrophysiological effects of NT on acutely dissociated NRM neurons.
The aim of the present study is to investigate the effects of orphanin FQ (OFQ) microinjected into the nucleus raphe magnus (NRM) and the nucleus reticularis gigantocellularis (NGC) on pain modulation.
Using immunohistochemical technique we found that the level of OFQ-like immunoreactivity was increased significantly in some pain-modulation-related nuclei, such as ventromedial hypothalamic nucleus, raphe magnus nucleus, dorsal raphe nucleus and periaqueductal gray (PAG) after intraperitoneal (i.p.) injection of MEL 60 mg/kg, and it was further enhanced while MEL combined with EA.
In order to determine whether serotonergic cells in the medullary raphe magnus (RM) receive baroreceptor input, cells were tested for their responses to descending aortic occlusion, aortic nerve stimulation, or systemic phenylephrine administration in the lightly anesthetized rat.
The expression of 5-hydroxytryptamine 5-HT2A receptor mRNA was studied in the lumbar spinal dorsal horn, nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) following carrageenan inflammation using in situ hybridization technique.
Nucleus raphe magnus (NRM) sends the projection to spinal dorsal horn and inhibits nociceptive transmission.
Slide-mounted brainstem sections, incubated in [ (125)I]BHSP and then exposed to film, have shown [ (125)I]BHSP binding throughout many brainstem nuclei and tracts, including the ambigual/periambigual (nAmb), dorsal motor vagal (dmnv), gigantocellular (nGC), hypoglossal (nHyp), medial parabrachial (nPBM), lateral reticular (nRL), raphe magnus (nRMg), raphe obscurus (nROb) and solitary tract (nTS) nuclei.
Neurons in the nucleus raphe magnus and adjacent structures of the rostral ventromedial medulla (RVM) are involved in the control of nociceptive transmission.
The expression of EP3 receptor by most of the serotonergic, noradrenergic and adrenergic cell groups suggests that prostaglandin E(2) modulates many physiological processes mediated by widely distributed monoaminergic projections through activation of the EP3 receptor on the monoaminergic neurons; for instance, it may modulate nociceptive and autonomic processes by affecting the descending serotonergic pathway from the raphe magnus nucleus to the spinal cord..
The spinal serotoninergic projection from the raphe magnus has been shown to modulate nociceptive inputs, and activation of this projection mediates nicotine-elicited analgesia.
It was examined whether or not the nucleus raphe dorsalis (RD) neurons projecting to the caudate-putamen (CPu) might also project to the motor-controlling region around the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (Gia) in the rat.
C-Fos expression at the lumbar laminae I-II level was significantly reduced, whereas it was significantly greater in the raphe magnus and pallidus nuclei in the double stimulation situation in wild-type compared with NK1-/- mice.
In this study, we evaluated whether different frequencies of electroacupuncture (EA) modified the activities of serotonergic neurons in the dorsal raphe (DR) and raphe magnus (RMg) using double labeling immunohistochemistry for Fos and serotonin.
Microinjection of metamizol (dipyrone), a widely used nonopioid analgesic, into the periaqueductal grey matter (PAG) of rats activates pain-modulating systems in the nucleus raphe magnus and inhibits spinal nociceptive neurons and the tail-flick reflex.
The nociceptive response latencies increased significantly after intra-nucleus raphe magnus administration of 0.1 or 0.4 nmol of neuropeptide Y, but not 0.04 nmol, in rats. The results indicate that NPY plays an antinociceptive role in nucleus raphe magnus in rats, which is mediated by the Y1 receptor. Furthermore, the neuropeptide Y-induced increases in hindpaw withdrawal latency were attenuated by following intra-nucleus raphe magnus injection of 6 nmol of the opioid antagonist naloxone, indicating that there is an interaction between NPY and opioids in nucleus raphe magnus..
After chronic administration of morphine, the oxytocin content in supraoptic nucleus (SON) and nucleus accumbens (NAc) decreased, and increased in the ventral tegment area (VTA) and locus coeruleus (LC), but did not change in other nuclei including the paraventricular nucleus (PVN), lateral septum (SEPTUM), raphe magnus nucleus (NRM) and periaquaductal gray (PAG).
Physiological studies in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis have identified putative nociceptive-inhibitory OFF cells and nociceptive-facilitatory neurons ON cells by their responses to noxious thermal stimulation.
The nucleus raphe magnus (NRM) is considered to be an important descending inhibitory system in the pain transmission.
The aim of this study was to determine the effects of descending modulatory control pathways on corneal unit activity by comparing the effects of conditioning stimulation of the pontine parabrachial area (PBA CS) and nucleus raphe magnus (NRM CS).
Compared with the findings in tolerant animals, the CNS of animals supersensitive to sufentanil showed less down-regulation of mu-opioid receptors, to the extent that, particularly in brain areas related to nociception, such as the somatosensory cortex, central grey, raphe magnus nucleus and dorsal horn of the spinal cord, no down-regulation occurred.
Only after a survival of 4 days or more, the locus coeruleus, the nucleus raphe magnus, the nucleus paragigantocellularis, pars alpha, and the pontine raphe nucleus were labeled.
The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats.
The descending serotonergic fibers, one of the inhibitory systems for nociceptive transmission, originate from the nucleus raphe magnus and terminate preferentially on SG of the spinal dorsal horn.
In the brain, the regions consistently labeled after all injections were the ventrolateral medulla, raphe magnus, raphe pallidus, A5, Barrington¹s nucleus, central gray, and paraventricular nucleus of the hypothalamus.
Occasional fibers and some terminals were observed in the nucleus of raphe magnus, parabrachial nucleus, and locus ceruleus.
raphe magnus, rostral and caudal ventrolateral medulla, and the nucleus tractus solitarii.
More modest immunoreactivity was seen in substantia nigra, nucleus raphe magnus, the ventral tegmental area, the pontine nuclei and the amygdala.
A preponderance of evidence suggests that nicotinic acetylcholine receptor agonists produce their analgesic effects predominantly via activation of descending inhibitory pain pathways originating in the key brainstem regions of the nucleus raphe magnus, dorsal raphe, and locus coeruleus, and that alpha4-containing nicotinic acetylcholine receptor subunits mediate these effects.
Calcitonin receptor mRNA was expressed in various brain regions, including the preoptic area, dorsomedial hypothalamic nucleus, lateral hypothalamic area, periaqueductal gray, dorsal raphe nucleus, locus coeruleus, lateral parabrachial nucleus, gigantocellular reticular nucleus alpha part, lateral paragigantocellular nucleus, raphe magnus nucleus and solitary tract nucleus, which are known to play important roles in pain modulation.
Cells in the nucleus raphe magnus that are inhibited by noxious skin stimuli (off-cells) have been postulated to suppress pain by continuously inhibiting spinal and trigeminal nociceptive neurons.
Intensely labeled cells were loosely scattered in the reticular formation adjacent to the raphe magnus and obscurus nuclei, in the gigantocellular region, in the caudal pedunculopontine and laterodorsal tegmental nuclei, dorsomedial pontine reticular formation, and nucleus subcoeruleus.
The relation between serotonin release and electrical activity was examined in the nucleus raphe magnus of rats anesthetized with pentobarbital.
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