Brain research
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Comparative Study
Ionotropic glutamate receptors mediate excitatory drive to caudal medullary expiratory neurons in the rabbit.
Most of the neurons of the caudal ventral respiratory group (cVRG) are bulbospinal expiratory neurons that receive their main excitatory drive from more rostral, but not yet defined regions. This study was devoted to investigate the functional role of ionotropic excitatory amino acid (EAA) receptors in the excitatory drive transmission to cVRG expiratory neurons during eupnoeic breathing and some respiratory reflexes including cough induced by mechanical stimulation of the tracheobronchial tree. The experiments were performed on spontaneously breathing rabbits under pentobarbitone anesthesia making use of microinjections (30--50 nl) of EAA receptor antagonists into the cVRG. ⋯ Spontaneous rhythmic abdominal activity and the reflex respiratory responses were strongly reduced, but not completely abolished by microinjections of 10 mM d(-)-2-amino-5-phosphonopentanoic acid (D-AP5), an NMDA antagonist. The results provide evidence that the excitatory drive to cVRG bulbospinal expiratory neurons during eupnoeic breathing and the investigated respiratory reflexes is mediated by EAA receptors. They also support the view that neurons located in the cVRG are not merely elements of the expiratory output system.
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Comparative Study
Spinal cord injury triggers sensitization of wide dynamic range dorsal horn neurons in segments rostral to the injury.
A spinal cord injury (SCI) was produced in adult rats by complete spinal cord transection at L6-S1. Neuropathic pain behaviors similar to the chronic central pain (CCP) syndrome in human, such as thermal hyperalgesia, mechanical allodynia and autotomy, were present in these rats after spinal cord injury. ⋯ It is suggested that spinal cord transection induces the CCP syndromes, which may be evoked and maintained by the hyperexcitability in WDR neurons rostrally. Reducing the neuronal activity at the site of lesion following injury may prevent the development of CCP after SCI.
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This study was designed to investigate the effect of acute and chronic intrathecal (i.t.) injection of gabapentin (GBP) on the antinociceptive effect of morphine and tolerance development using a tail-flick latency test. Levels of excitatory amino acids (EAA) in i.t. CSF dialysates were also measured by high performance liquid chromatography. ⋯ Acute injection of GBP (10 microg i.t.), morphine (50 microg i.t.), or GBP (10 microg i.t.) followed by morphine (50 microg i.t.) 30 min later had no significant effect on CSF EAA concentration in naïve rats; however, in tolerant rats, morphine challenge (50 microg i.t.) increased aspartate and glutamate levels to 221 +/- 22% and 296 +/- 43%, respectively, of those before morphine challenge, and this phenomenon was inhibited by GBP co-infusion. Our results show that GBP, at a dose without enhanced effect on morphine's antinociception in naïve rats, not only potentiates morphine's antinociceptive effect in morphine-tolerant rats but also attenuates the development of morphine tolerance. The mechanism of the effect of GBP on morphine tolerance might be via suppression of the EAA concentration in spinal CSF dialysate.
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Comparative Study
NOC/oFQ activates ERK and JNK but not p38 MAPK to impair prostaglandin cerebrovasodilation after brain injury.
Fluid percussion brain injury (FPI) elevates the CSF concentration of the opioid nociceptin/orphanin FQ (NOC/oFQ), which contributes to impairment of pial artery dilation to the prostaglandins (PG) PGE2 and PGI2. This study investigated the role of the ERK, p38, and JNK isoforms of mitogen-activated protein kinase (MAPK) in impaired PG cerebrovasodilation after FPI, and the relationship of brain injury induced release of NOC/oFQ to MAPK in such vascular impairment in newborn pigs equipped with a closed cranial window. FPI blunted PGE2 pial artery dilation, but U 0126 and SP 600125 (10(-6) M) (ERK and JNK MAPK inhibitors, respectively) partially prevented such impairment (7 +/- 1, 12 +/- 1, and 17 +/- 1 vs. 2 +/- 1, 3 +/- 1, and 5 +/- 1 vs. 4 +/- 1, 7 +/- 1, and 12 +/- 1% for 1, 10, and 100 ng/ml PGE2 in control, FPI, and FPI + U 0126 pretreated animals, respectively). ⋯ Administration of SB 203580 did not prevent impairment of PG pial artery dilation by NOC/oFQ. These data show that activation of ERK and JNK but not p38 MAPK contributes to impairment of PG cerebrovasodilation after FPI. These data suggest that NOC/oFQ induced ERK and JNK but not p38 MAPK activation contributes to impaired cerebrovasodilation to PG after FPI.
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Comparative Study
Orexin fibers form appositions with Fos expressing neuropeptide-Y cells in the grass rat intergeniculate leaflet.
Neuropeptide-Y (NPY) cells in the intergeniculate leaflet (IGL) are known to modulate effects of arousal on the mammalian circadian system. However, the route through which this information reaches the IGL has not been established. ⋯ Specifically, many NPY cells in the grass rat IGL exhibit orexin-A (OXA) fiber appositions. Furthermore, NPY cells contacted by OXA fibers are significantly more likely to express Fos during nocturnal wheel running than are NPY cells without such contacts (P < 0.001).