Magnesium as an adjuvant for caudal analgesia in children.

BACKGROUND: There is a need for an adjuvant agent of caudal block that prolongs its duration and improves the analgesic efficacy to fasten functional recovery. Magnesium is an N-methyl-D-aspartate receptor antagonist that functions as an analgesic. This study was aimed to evaluate whether magnesium as an adjuvant for caudal block in children can improve postoperative analgesia and functional recovery. METHODS: Eighty children, 2-6 years of age, undergoing inguinal herniorrhaphy, were included in this prospective, randomized, double-blinded study. For caudal block, Group R received ropivacaine 1.5 mg·ml(-1), 1 ml·kg(-1) and Group RM received the same dose of ropivacaine mixed with 50 mg of magnesium. The Parents' Postoperative Pain Measure (PPPM) score, analgesic consumption, functional recovery, and adverse effects were evaluated at 6, 24, 48, and 72 h after surgery, as well as daily thereafter until the child showed full functional recovery. RESULTS: The PPPM score after hospital discharge was significantly lower for Group RM than for Group R at all times (P < 0.05). Children in Group RM required less fentanyl for rescue analgesia in the recovery area (16.2% vs 39.5%, P = 0.034) and less oral analgesics after discharge (20.5% vs 52.6%, P = 0.007). The time to return of normal functional activity was shorter in Group RM (P < 0.05). The incidence of adverse effects did not differ between groups. CONCLUSIONS: As an adjuvant for caudal analgesia, 50 mg magnesium provided superior quality of analgesia and faster return of normal functional activity than local anesthetic alone in children.

N-Docosahexaenoylethanolamide promotes development of hippocampal neurons.

DHA (docosahexaenoic acid, C22:6,n-3) has been shown to promote neurite growth and synaptogenesis in embryonic hippocampal neurons, supporting the importance of DHA known for hippocampus-related learning and memory function. In the present study, we demonstrate that DHA metabolism to DEA (N-docosahexaenoylethanolamide) is a significant mechanism for hippocampal neuronal development, contributing to synaptic function. We found that a fatty acid amide hydrolase inhibitor URB597 potentiates DHA-induced neurite growth, synaptogenesis and synaptic protein expression. Active metabolism of DHA to DEA was observed in embryonic day 18 hippocampal neuronal cultures, which was increased further by URB597. Synthetic DEA promoted hippocampal neurite growth and synaptogenesis at substantially lower concentrations in comparison with DHA. DEA-treated neurons increased the expression of synapsins and glutamate receptor subunits and exhibited enhanced glutamatergic synaptic activity, as was the case for DHA. The DEA level in mouse fetal hippocampi was altered according to the maternal dietary supply of n-3 fatty acids, suggesting that DEA formation is a relevant in vivo process responding to the DHA status. In conclusion, DHA metabolism to DEA is a significant biochemical mechanism for neurite growth, synaptogenesis and synaptic protein expression, leading to enhanced glutamatergic synaptic function. The novel DEA-dependent mechanism offers a new molecular insight into hippocampal neurodevelopment and function.

Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis.

There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine- and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse.