Brain research bulletin
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Brain research bulletin · Aug 2014
Inhibition of p38 mitogen-activated protein kinase activation in the rostral anterior cingulate cortex attenuates pain-related negative emotion in rats.
The emotional components of pain are far less studied than the sensory components. Previous studies have indicated that the rostral anterior cingulate cortex (rACC) is implicated in the affective response to noxious stimuli. Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been documented to play an important role in diverse kinds of pathological pain states. ⋯ Inhibiting p38 MAPK activation did not affect formalin-induced two-phase spontaneous nociceptive response and low intensity electric foot-shock induced CPA. The present study demonstrated that p38 MAPK signaling pathway in the rACC contributes to pain-related negative emotion. Thus, a new pharmacological strategy targeted at the p38 MAPK cascade may be useful in treating pain-related emotional disorders.
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Brain research bulletin · Jul 2014
Intrathecal administration of roscovitine prevents remifentanil-induced postoperative hyperalgesia and decreases the phosphorylation of N-methyl-D-aspartate receptor and metabotropic glutamate receptor 5 in spinal cord.
N-methyl-D-aspartate receptor (NMDAR) and metabotropic glutamate receptor 5 (mGluR5) play an important role in nociceptive processing and central sensitization. Our previous study showed that tyrosine phosphorylation of NMDAR subunit 2B (NR2B) at Tyr1472 in spinal dorsal horn contributes to the postoperative hyperalgesia induced by remifentanil. Cyclin-dependent kinase 5 (Cdk5) has been implicated in synaptic plasticity, learning, memory and pain signaling via regulating the phosphorylation of NMDAR and mGluR5. ⋯ Furthermore, these increases were attenuated by pretreatment with roscovitine. These results suggested that Cdk5 may contribute to remifentanil-induced postoperative hyperalgesia via regulating the phosphorylation of NMDAR and mGluR5 in spinal dorsal horn. These findings provide experimental evidence for the further application of Cdk5 inhibitor in preventing remifentanil-induced hyperalgesia.
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Brain research bulletin · Jul 2014
Hydrogen-rich saline controls remifentanil-induced hypernociception and NMDA receptor NR1 subunit membrane trafficking through GSK-3β in the DRG in rats.
Although NMDAR trafficking mediated by GSK-3β involvement in transmission of pronociceptive messages in the spinal cord has been confirmed by our previous studies, whether NMDAR trafficking is implicated in peripheral sensitization remains equivocal. It is demonstrated that inflammation is associated with spinal NMDAR-containing nociceptive neurons activation and the maintenance of opioid induced pain hypersensitivity. However, whether and how hydrogen-rich saline, as an effective anti-inflammatory drug, could prevent hyperalgesia through affecting peripheral sensitization caused by NMDAR activation remains to be explored. ⋯ Our results indicated that antihyperalgesic effect of hydrogen-rich saline might depend predominantly on its ability to reverse NR1 trafficking via inhibition of GSK-3β activity in DRG in a dose-dependent manner.
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Brain research bulletin · Jul 2014
Expression of transient receptor potential vanilloid 1 and anoctamin 1 in rat trigeminal ganglion neurons innervating the tongue.
Transient receptor potential vanilloid 1 (TRPV1) is a polymodal sensor that is activated by heat (>43 °C), acid, or capsaicin, the pungent ingredient of hot peppers. Reports that mice lacking TRPV1 display heat avoidance behaviors and TRPV1-negative neurons respond to heat suggest that an additional heat sensor is present. Anoctamin 1 (ANO1; also known as transmembrane protein 16A [TMEM16A]), is a component of Ca(2+)-activated chloride channels (CaCCs), and has been recently identified as a heat sensor, activated by temperatures over 44 °C. ⋯ The FG-labeled TG neurons showed TRPV1 immunoreactivity (17.9%) and ANO1 immunoreactivity (13.7%), indicating that TRPV1- and ANO1-expressing neurons were present in the mandibular division of the TGs. Seventy-six percent of the ANO1-immunoreactive TG neurons were also immunoreactive for TRPV1; this co-expression was mainly detected in small- to medium-diameter TG neurons. The high degree of co-expression of TRPV1 and ANO1 suggests that cooperation between ANO1 and TRPV1 plays a role in the signaling pathways of nociceptive TG neurons.
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Brain research bulletin · May 2014
Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: possible role of l-arginine-NO-cGMP pathway and BDNF levels.
Hesperidin (4'-methoxy-7-O-rutinosyl-3',5-dihydroxyflavanone), a naturally occurring flavanone glycoside, was previously shown to produce an antidepressant-like effect with modultation of the serotonergic 5-HT1A and kappa-opioid receptors. In this study, the signaling mechanisms underlying their antidepressant-like effects were further evaluated by investigating in acute and chronic treatments. Results showed that chronic treatment of hesperidin or hesperitin (0.1, 0.3 and 1mg/kg, intraperitoneal, i.p.) have an antidepressant-like effect in the mouse tail suspension test (TST) without modified the locomotor activity in the open field test. ⋯ Hesperidin in the acute (1mg/kg) and chronic (0.1, 0.3 and 1mg/kg) treatments caused a significant decrease in nitrate/nitrite (NOX) levels in the hippocampus of mice. Chronic treatment with hesperidin (0.3 and 1mg/kg) also resulted in an increase in hippocampal brain-derived neurotrophic factor (BDNF) levels. These results demonstrated that the antidepressant-like effect of hesperidin is likely mediated by inhibition of l-arginine-NO-cGMP pathway and by increased of the BDNF levels in hippocampus.