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Rostral Ventromedial Medulla (rostral + ventromedial_medulla)
Selected AbstractsINVOLVEMENT OF N -METHYL- d -ASPARTATE RECEPTORS and NITRIC OXIDE IN THE ROSTRAL VENTROMEDIAL MEDULLA IN MODULATING MORPHINE PAIN-INHIBITORY SIGNALS FROM THE PERIAQUEDUCTAL GREY MATTER IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2005Kazem Javanmardi SUMMARY 1.,Supraspinal opioid antinociception is mediated, in part, by connections between the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Morphine antinociception from the PAG is decreased by serotonin, N -methyl- d -aspartate (NMDA) and opioid receptor antagonists administered into the RVM. Because the brain isoform of nitric oxide synthase (NOS) is also prominent in the RVM, the present study was designed to evaluate the effects of microinjection of the non-selective NOS inhibitor NG -nitro- l -arginine methyl ester (l -NAME) and the non-competitive NMDA receptor antagonist MK-801 into the RVM on PAG morphine antinociception and their potential interactions, as measured by the tail-flick test. 2.,Rats were anaesthetized with sodium pentobarbital and then special cannulas were inserted stereotaxically into the RVM and PAG. After 1 week recovery, the effects of microinjection of MK-801 and l -NAME into the RVM and their interactions in altering PAG morphine (2.5 µg) antinociception elicited from the PAG were assessed. 3.,Mesencephalic morphine antinociception was significantly reduced after pretreatment with l -NAME (0.6,1.3 µmol) or MK-801 (0.8 nmol). The reduction in mesencephalic morphine antinociception when MK-801 (0.8 nmol) and l -NAME (1 µmol) were microinjected sequentially into the RVM was not significantly different from the effects of MK-801 (0.8 nmol) or l -NAME (1 µmol) administered alone. 4.,These data imply that NMDA receptors and nitric oxide production in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG. [source] Tolerance to non-opioid analgesics in PAG involves unresponsiveness of medullary pain-modulating neurons in male ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Victor Tortorici Abstract Opiate analgesia can be hampered by a reduction in pharmacological effectiveness (tolerance), and this crucially depends on the periaqueductal gray matter (PAG). Non-opioids like metamizol (dipyrone) or aspirin also induce PAG-dependent analgesia and tolerance, but the neuronal bases of this tolerance are unknown. Metamizol is a pyrazolon derivative and cyclooxygenase inhibitor with widespread use as an analgesic in Europe and Latin America. Metamizol was microinjected into the PAG of awake male rats, and antinociception was assessed by the tail flick (TF) and hot plate (HP) tests. Microinjection twice daily for 2.5 days caused tolerance to metamizol. The rats were then anesthetized and recordings from pain-facilitating on-cells and pain-inhibiting off-cells of the rostral ventromedial medulla (RVM) were performed. PAG microinjection of morphine or metamizol depresses on-cells, activates off-cells and thus inhibits nociception, including TF and HP. In metamizol-tolerant rats, however, PAG microinjection of metamizol failed to affect on- or off-cells, and this is interpreted as the reason for tolerance. In metamizol-tolerant rats morphine microinjection into PAG also failed to affect RVM neurons or nociception (cross-tolerance). In naïve, non-tolerant rats the antinociceptive effect of PAG-microinjected metamizol or morphine was blocked when CTOP, a ,-opioid antagonist, was previously microinjected into the same PAG site. These results emphasize a close relationship between opioid and non-opioid analgesic mechanisms in the PAG and show that, like morphine, tolerance to metamizol involves a failure of on- and off-cells to, respectively, disfacilitate and inhibit nociception. Cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting. [source] Central control of thermogenesis in mammalsEXPERIMENTAL PHYSIOLOGY, Issue 7 2008Shaun F. Morrison Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature in mammals and birds during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. The primary sources of neurally regulated metabolic heat production are mitochondrial oxidation in brown adipose tissue, increases in heart rate and shivering in skeletal muscle. Thermogenesis is regulated in each of these tissues by parallel networks in the central nervous system, which respond to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate the appropriate sympathetic and somatic efferents. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates thermogenesis and discusses the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature. The cold thermal afferent circuit from cutaneous thermal receptors ascends via second-order thermosensory neurons in the dorsal horn of the spinal cord to activate neurons in the lateral parabrachial nucleus, which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus and possibly of sympathetic and somatic premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, activates excitatory inputs to spinal sympathetic and somatic motor circuits to drive thermogenesis. [source] The effects of local perfusion of DAMGO on extracellular GABA and glutamate concentrations in the rostral ventromedial medullaJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Raf Jan-Filip Schepers Abstract Electrophysiological data suggest an involvement of rostral ventromedial medulla (RVM) GABA and glutamate (GLU) neurons in morphine analgesia. Direct evidence that extracellular concentrations of GABA or GLU are altered in response to mu opioid receptor (MOP-R) activation is, however, lacking. We used in vivo microdialysis to investigate this issue. Basal GABA overflow increased in response to intra-RVM perfusion of KCl (60 mmol/L). Reverse microdialysis of the MOP-R agonist d -Ala(2),NMePhe(4),Gly-ol(5)]enkephalin (DAMGO) (20,500 ,mol/L) produced a concentration-dependent decrease of RVM GABA overflow. Behavioral testing revealed that concentrations that decreased GABA levels increased thermal withdrawal thresholds. A lower agonist concentration that did not increase GABA failed to alter thermal thresholds. DAMGO did not alter GLU concentrations. However, KCl also failed to modify GLU release. Since rapid, transporter-mediated uptake may mask the detection of changes in GLU release, the selective excitatory amino acid transporter inhibitor pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mmol/L) was added to the perfusion medium for subsequent studies. tPDC increased GLU concentrations, confirming transport inhibition. KCl increased GLU dialysate levels in the presence of tPDC, demonstrating that transport inhibition permits detection of depolarization-evoked GLU overflow. In the presence of tPDC, DAMGO increased GLU overflow in a concentration-dependent manner. These data demonstrate that MOP-R activation decreases GABA and increases GLU release in the RVM. We hypothesize that the opposing effects of MOP-R on GLU and GABA transmission contribute to opiate antinociception. [source] GABAergic and glycinergic presympathetic neurons of rat medulla oblongata identified by retrograde transport of pseudorabies virus and in situ hybridizationTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2004Ruth L. Stornetta Abstract Electron microscopy suggests that up to half the synaptic input to sympathetic preganglionic neurons (SPGNs) is GABAergic or glycinergic. A proportion of this input is suspected to originate from neurons located within the medulla oblongata. The present study provides definitive evidence for the existence of these supraspinal presympathetic (PS) neurons with inhibitory phenotypes. PS neurons were identified by retrograde trans-synaptic migration of pseudorabies virus (PRV) injected into the adrenal gland. GABAergic or glycinergic cell bodies were identified by the presence of glutamate decarboxylase (GAD)-67 mRNA or glycine transporter (GlyT)-2 mRNA detected with in situ hybridization (ISH). Neither GABAergic nor glycinergic PS neurons were tyrosine hydroxylase (TH)-immunoreactive (ir). GABAergic PS neurons were located within the ventral gigantocellular nucleus, gigantocellular nucleus alpha, and medial reticular formation, mostly medial to the TH-ir PS neurons. About 30% of GABAergic PS neurons were serotonergic cells located in the raphe pallidus (RPa) and parapyramidal region (PPyr). Glycinergic PS neurons had the same general distribution as the GABAergic cells, except that no glycinergic neurons were located in the RPa or PPyr and none were serotonergic. PRV immunohistochemistry combined with ISH for both GlyT2 and GAD-67 mRNAs showed that at least 63% of midline medulla GABAergic PS neurons were also glycinergic and 76% of glycinergic PS neurons were GABAergic. In conclusion, the rostral ventromedial medulla contains large numbers of GABAergic and glycinergic neurons that innervate adrenal gland SPGNs. Over half of these PS neurons may release both transmitters. The physiological role of this medullary inhibitory input remains to be explored. J. Comp. Neurol. 479:257,270, 2004. © 2004 Wiley-Liss, Inc. [source] Medullary pain facilitating neurons mediate allodynia in headache-related pain,ANNALS OF NEUROLOGY, Issue 2 2009Rebecca M. Edelmayer BS Objective To develop and validate a model of cutaneous allodynia triggered by dural inflammation for pain associated with headaches. To explore neural mechanisms underlying cephalic and extracephalic allodynia. Methods Inflammatory mediators (IM) were applied to the dura of unanesthetized rats via previously implanted cannulas, and sensory thresholds of the face and hind-paws were characterized. Results IM elicited robust facial and hind-paw allodynia, which peaked within 3 hours. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in the treatment of migraine, including sumatriptan, naproxen, and a calcitonin gene,related peptide antagonist. Consistent with clinical observations, the allodynia was unaffected by a neurokinin-1 antagonist. Having established facial and hind-paw allodynia as a useful animal surrogate of headache-associated allodynia, we next showed that blocking pain-facilitating processes in the rostral ventromedial medulla (RVM) interfered with its expression. Bupivacaine, destruction of putative pain-facilitating neurons, or block of cholecystokinin receptors prevented or significantly attenuated IM-induced allodynia. Electrophysiological studies confirmed activation of pain-facilitating RVM "on" cells and transient suppression of RVM "off" cells after IM. Interpretation Facial and hind-paw allodynia associated with dural stimulation is a useful surrogate of pain associated with primary headache including migraine and may be exploited mechanistically for development of novel therapeutic strategies for headache pain. The data also demonstrate the requirement for activation of descending facilitation from the RVM for the expression of cranial and extracranial cutaneous allodynia, and are consistent with a brainstem generator of allodynia associated with headache disorders. Ann Neurol 2009;65:184,193 [source] INVOLVEMENT OF N -METHYL- d -ASPARTATE RECEPTORS and NITRIC OXIDE IN THE ROSTRAL VENTROMEDIAL MEDULLA IN MODULATING MORPHINE PAIN-INHIBITORY SIGNALS FROM THE PERIAQUEDUCTAL GREY MATTER IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2005Kazem Javanmardi SUMMARY 1.,Supraspinal opioid antinociception is mediated, in part, by connections between the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Morphine antinociception from the PAG is decreased by serotonin, N -methyl- d -aspartate (NMDA) and opioid receptor antagonists administered into the RVM. Because the brain isoform of nitric oxide synthase (NOS) is also prominent in the RVM, the present study was designed to evaluate the effects of microinjection of the non-selective NOS inhibitor NG -nitro- l -arginine methyl ester (l -NAME) and the non-competitive NMDA receptor antagonist MK-801 into the RVM on PAG morphine antinociception and their potential interactions, as measured by the tail-flick test. 2.,Rats were anaesthetized with sodium pentobarbital and then special cannulas were inserted stereotaxically into the RVM and PAG. After 1 week recovery, the effects of microinjection of MK-801 and l -NAME into the RVM and their interactions in altering PAG morphine (2.5 µg) antinociception elicited from the PAG were assessed. 3.,Mesencephalic morphine antinociception was significantly reduced after pretreatment with l -NAME (0.6,1.3 µmol) or MK-801 (0.8 nmol). The reduction in mesencephalic morphine antinociception when MK-801 (0.8 nmol) and l -NAME (1 µmol) were microinjected sequentially into the RVM was not significantly different from the effects of MK-801 (0.8 nmol) or l -NAME (1 µmol) administered alone. 4.,These data imply that NMDA receptors and nitric oxide production in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG. [source] | |||||||||||||