Neuroscience letters
-
Neuroscience letters · Oct 2010
Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat.
We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. ⋯ We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states.
-
Neuroscience letters · Oct 2010
Restriction of rear-up-behavior-induced attenuation of vestibulo-cardiovascular reflex in rats.
Previously, we have demonstrated that the vestibulo-cardiovascular reflex was attenuated in rats reared in a 3G environment for 14 days. Because continuous galvanic vestibular stimulation preserved the vestibulo-cardiovascular reflex in rats at 3G, this attenuation might be attributable to a reduction in the phasic input to the vestibular system. The present study shows that the head movements of rats were significantly suppressed in the 3G environment. ⋯ The suppressive effect of the low-roof cage was similar to that of 3G. There was no difference in the air-jet-induced pressor response among three groups (rats reared in a usual 1G environment, rats reared in the low-roof cage, and rats reared in the 3G environment), suggesting that the sensitivity of the vestibulo-cardiovascular reflex was selectively suppressed. These results indicate that a reduction in the vestibular phasic input acts to attenuate the vestibulo-cardiovascular reflex.
-
Neuroscience letters · Oct 2010
CC-chemokine MIP-1α in the spinal cord contributes to nerve injury-induced neuropathic pain.
We investigated the involvement of spinal macrophage inflammatory protein-1α (MIP-1α), an inflammatory chemokine, in partial sciatic nerve ligation (PSL)-induced neuropathic pain in mice. PSL increased MIP-1α mRNA levels as well as levels of the MIP-1α receptor, CCR1, but not CCR5 in the spinal dorsal horn. ⋯ Recombinant MIP-1α (10pmol, i.t.) elicited long-lasting tactile allodynia and thermal hyperalgesia in naïve mice. These results suggest that peripheral nerve injury elicits the up-regulation of spinal MIP-1α and CCR1 to participate in neuropathic pain.
-
Neuroscience letters · Oct 2010
Clinical TrialPlasma orexin A increases at emergence from sevoflurane-fentanyl anesthesia in patients undergoing ophthalmologic surgery.
Central orexinergic and noradrenergic neurons are involved in the control of sleep and wakefulness. In addition, previous reports suggest that both neurons may have an important role to play in general anesthesia. In the present study, we have determined whether general anesthesia would affect plasma orexin A (OXA) and norepinephrine concentrations. ⋯ Plasma OXA, cortisol, norepinephrine and epinephrine did not change during anesthesia but significantly increased after emergence compared to pre-anesthesia (from 14.8+/-1.7 to 21.4+/-1.7 pM, p<0.01, from 26.5+/-5.2 to 52.8+/-6.0 pM, p<0.01, from 263+/-46 to 513+/-89 pM, p<0.01, and from 1239+/-120 to 1631+/-203 pM, p<0.01, respectively). There were significant correlations of plasma OXA with cortisol (r=0.334, p<0.05) and epinephrine (r=0.292, p<0.05) but not with norepinephrine. In conclusion we found that plasma OXA significantly increased at emergence from sevoflurane-fentanyl anesthesia and this was probably via activation of the hypothalamic-pituitary-adrenal axis.
-
Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, induces apoptosis in microglia, but the underlying mechanism by which microglia apoptosis in response to VPA is not yet known. In this study, we found that the mitochondrial pathway played an important role in VPA-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. ⋯ Moreover, p38 inhibitor SB203580 strongly inhibited VPA-induced apoptosis and caspase-3 activation. Taken together, our results clearly demonstrated that VPA could induce apoptosis of microglia via p38 MAPK and mitochondrial apoptosis pathway.