Neuroscience letters
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Neuroscience letters · Jun 2005
Noise-induced cell death in the mouse medial geniculate body and primary auditory cortex.
Noise-induced effects within the inner ear have been well investigated for several years. However, this peripheral damage cannot fully explain the audiological symptoms in noise-induced hearing loss (NIHL), e.g. tinnitus, recruitment, reduced speech intelligibility, hyperacusis. There are few reports on central noise effects. ⋯ Cell density was significantly reduced in all subdivisions of the MGB and in layers IV-VI of AI. The present findings demonstrate a significant noise-induced change of the neuronal cytoarchitecture in central key areas of auditory processing. These changes could contribute to the complex psychoacoustic symptoms after NIHL.
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Neuroscience letters · Jun 2005
Multiple kinase pathways mediate the early sciatic ligation-associated activation of CREB in the rat spinal dorsal horn.
Phosphorylation of the cyclic AMP response element-binding protein (CREB) in the spinal dorsal horn may critically contribute to chronic pain following peripheral nerve injury. We employed inhibitors and activators of protein kinase A (PKA), protein kinase C (PKC), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and calcium/calmodulin-dependent kinase II (CaMKII) to examine whether these kinases individually or in concert mediate the increase in CREB phosphorylation that is evident as early as 2 h after loose ligation of the sciatic nerve. Specific inhibitors of each kinase significantly attenuated the ligation-associated CREB phosphorylation when compared to saline-treated animals. ⋯ Significant increases in ERK1/2 phosphorylation were also detected 2 h after sciatic ligation confirming a role for the ERK pathway in injury-related responses in the dorsal horn. Each kinase inhibitor significantly attenuated the ligation-associated activation of ERK1/2 as well. These data suggest that early, sciatic ligation-elicited phosphorylation of CREB in the spinal dorsal horn is mediated by multiple kinase pathways, and that PKA, PKC and CaMKII activate CREB at least in part by way of the ERK pathway.
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Neuroscience letters · Jun 2005
Modulation of peripheral inflammation in sensory ganglia by nuclear factor (kappa)B decoy oligodeoxynucleotide: involvement of SRC kinase pathway.
Nuclear factor kappa B (NF(kappa)B) transcription factor plays a key role in the expression of many genes involved in the inflammatory process. We used the Freund's Complete Adjuvant (FCA)-induced model of peripheral inflammation to investigate the anti-inflammatory effects of double stranded oligodeoxynucleotides (ODN) with consensus NF(kappa)B sequence as transcription factor decoys to inhibit NF(kappa)kappaB activation in the dorsal root ganglia (DRG). ⋯ The present results indicate that the wild-type ODN decoy may act as a competitor for NF(kappa)B binding to its cognate recognition sequence as well as a modulator of c-Src activity in the DRG. The NF(kappa)B/c-Src interaction may represent a novel pathway for further exploring the molecular mechanism of inflammatory pain.
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Neuroscience letters · Jun 2005
Homotopic and heterotopic effects of endogenous analgesia in healthy volunteers.
Although research on DNIC has revealed the inhibitory effect occurring between two remote pain stimuli, the interrelation between two adjacent painful stimuli has not yet been characterized. In the present study, we used a sample of 40 healthy volunteers to examine the effect of 30-s immersion of the fingers in water of 1 degree C, as a conditioning stimulus, on pain intensities produced by conditioned mechanical punctuate stimuli, applied both adjacent and contralateral to the cooled area. ⋯ The extent of pain reduction following cooling in the cooled and in the uncooled hand was also found to be similar for males and for females (p=0.63). It is concluded that under the conditions of this experiment, EA affects heterotopic and homotopic regions similarly and without gender differences.
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Neuroscience letters · May 2005
Comparative StudySpinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P-p38.
Spinal nerve ligation (SNL) results in a profound long lasting allodynia and increases in phosphorylated p38 in dorsal root ganglia (DRG) neurons and spinal cord microglia. We have previously shown that systemic etanercept, a tumor necrosis factor (TNF) antagonist, reduced allodynia by 42% and blocked SNL-induced increases in P-p38 levels in the L5 and L6 DRG, but not in the ipsilateral lumbar spinal cord. The present experiments demonstrated that intrathecal etanercept (100 microg) prevents SNL-induced increased levels of spinal P-p38. ⋯ This therapeutic benefit was maintained for at least 7 days after cessation of treatment. Combined systemic and intrathecal administration of etanercept was no more effective than intrathecal treatment alone. These data imply that TNF provides the trigger for phosphorylation of p38 in both DRG neurons and spinal microglia.