Neuroscience letters
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Neuroscience letters · Apr 2006
NSAID zaltoprofen possesses novel anti-nociceptive mechanism through blockage of B2-type bradykinin receptor in nerve endings.
Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs (NSAIDs), was shown to have more powerful inhibitory effects to bradykinin (BK)-nociception than other NSAIDs. However, the molecular mechanisms underlying this potent analgesia are not yet fully understood. Here we attempted to clarify the molecular mechanism underlying zaltoprofen-induced analgesia on BK-induced nociception by a novel algogenic-induced paw flexion (APF) test in mice. ⋯ Zaltoprofen also inhibited the nociception induced by [Tyr8]-BK, a specific agonist of B2-type BK receptor, but did not affect the nociception by [Lys-des-Arg9]-BK, a specific agonist of B1-type BK receptor. However, zaltoprofen did not affect the substance P-induced nociception, which is mediated by common post-receptor signaling through nociceptive fibers with BK-ones. All these results suggest that NSAID zaltoprofen possesses novel anti-nociceptive mechanism, which inhibits B2-type BK receptor function in nerve endings.
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Neuroscience letters · Apr 2006
Comparative StudyOptical coherence tomography reveals in vivo cortical plasticity of adult mice in response to peripheral neuropathic pain.
We examined neural plasticity in mice in vivo using optical coherence tomography (OCT) of primary somatosensory (S1) and motor (M1) cortices of mice under the influence of sciatic nerve chronic constriction injury (CCI), a model of neuropathic pain widely utilized in rats. The OCT system used in this study provided cross-sectional images of the cortical tissue of mice up to a depth of about 1mm with longitudinal resolution up to 11 microm. This is the first study to evaluate neural plasticity in vivo using OCT. ⋯ Synapses and mitochondria are believed to have high light scattering coefficients, since they contain remarkably high concentrations of proteins and complicated membrane structure. Number densities of mitochondria and synapses are known to increase in parallel with increases in neural activity. Our findings thus suggest that neuropathic pain gives rise to neural plasticity within the hind paw area of S1 and M1 contralateral to the ligated sciatic nerve.
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Neuroscience letters · Mar 2006
Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells.
Adenosine is an endogenous nucleoside that regulates many processes, including inflammatory responses, through activation of its receptors. Adenosine receptors have been reported to be expressed in microglia, which are major immune cells of brain, yet little is known about the role of adenosine receptors in microglial cytokine production. Thus, we investigated the effect of adenosine and adenosine A3 receptor ligands on LPS-induced tumor necrosis factor (TNF-alpha) production and its molecular mechanism in mouse BV2 microglial cells. ⋯ Adenosine inhibited LPS-induced phosphatidylinositol (PI) 3-kinase activation and Akt phosphorylation, whereas it had no effect on the phosphorylation of p38 and ERK1/2. We also found that adenosine as well as Cl-IB-MECA inhibited LPS-induced NF-kappaB DNA binding and luciferase reporter activity. Taken together, these results suggest that adenosine A3 receptor activation suppresses TNF-alpha production by inhibiting PI 3-kinase/Akt and NF-kappaB activation in LPS-treated BV2 microglial cells.
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Neuroscience letters · Mar 2006
Comparative StudyComparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.
Na(+) channel blockers are highly effective analgesics. Among the neuronal Na(+) channel subtypes, Nav1.8 is discussed to be of importance for certain pain states, and Nav1.8-preferring Na(+) channel blockers should be able to relief pain without causing severe effects (due to the restricted expression of this channel type). In this study, the effects of four Na(+) channel blockers on rat tetrodotoxin-resistant (TTX-r) Na(+) channels (representing mostly Nav1.8) in sensory neurons were investigated using the patch-clamp technique in the voltage-clamp configuration, and compared with those on cells heterologously expressing Nav1.2 alpha subunits. ⋯ All compounds shifted steady-state inactivation curves to more negative values. Ambroxol blocked resting TTX-r channels more potently than Nav1.2, the opposite was the case for lidocaine, mexiletine and benzocaine. Based on the drugs' potencies found in this study, and the published information on clinically achievable plasma levels, the amount of Na(+) channel block to induce analgesia after systemic administration was estimated.
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Neuroscience letters · Feb 2006
Complement activation after lumbosacral ventral root avulsion injury.
A lumbosacral ventral root avulsion (VRA) injury results in a pronounced loss of motoneurons, in part due to apoptosis. Caspase inhibitors may rescue motoneurons after a VRA in neonatal rats, but this treatment approach has been unsuccessful to protect motoneurons subjected to the same injury in adult rats. Other mechanisms may contribute to the retrograde motoneuron death encountered in adult animals. ⋯ The MAC inhibitor Clusterin was concurrently expressed at significantly higher levels in astrocytes and de novo in 30% of the remaining motoneurons. Our data suggest that complement activation and necrosis contribute to motoneuron death after lumbosacral VRA injuries. We speculate that inhibition of MAC may constitute a potential neuroprotective strategy following cauda equina injuries.