GlyT1 Inhibition by NFPS Promotes Neuroprotection in Amyloid-ß-Induced Alzheimer's Disease Animal Model.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-ß, leading to N-methyl-D-aspartate (NMDA) receptor-dependent synaptic depression, spine elimination, and memory deficits. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission via NMDA receptors (NMDAR), presenting a potential alternative therapeutic approach for AD. This study investigates the neuroprotective potential of GlyT1 inhibition in an amyloid-ß-induced AD mouse model. C57BL/6 mice were treated with N-[3-([1,1-Biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine (NFPS), a GlyT1 inhibitor, 24 h prior to intrahippocampal injection of amyloid-ß. NFPS pretreatment prevented amyloid-ß-induced cognitive deficits in short-term and long-term memory, evidenced by novel object recognition and spatial memory tasks. Moreover, NFPS pretreatment curbed microglial activation, astrocytic reactivity, and subsequent neuronal damage from amyloid-ß injection. An extensive label-free quantitative UPLC-MSE proteomic analysis was performed on the hippocampi of mice treated with NFPS. In proteomics, KEGG enrichment analysis revealed increased in dopaminergic synapse, purine-containing compound biosynthetic process and long-term potentiation, and a reduction in Glucose catabolic process and glycolytic process pathways. The western blot analysis confirmed that NFPS treatment elevated BDNF levels, correlating with enhanced TRKB phosphorylation and mTOR activation. Moreover, NFPS treatment reduced the GluN2B expression after 6 h, which was associated with an increase on CaMKIV and CREB phosphorylation. Collectively, these findings demonstrate that GlyT1 inhibition by NFPS activates diverse neuroprotective pathways, enhancing long-term potentiation signaling and countering amyloid-ß-induced hippocampal damage.

Novel Proline Transporter Inhibitor (LQFM215) Presents Antipsychotic Effect in Ketamine Model of Schizophrenia.

The glutamatergic hypothesis of schizophrenia suggests a correlation between NMDA receptor hypofunction and negative psychotic symptoms. It has been observed that the expression of the proline transporter (PROT) in the central nervous system (CNS) is associated with glutamatergic neurotransmission, as L-proline has the capacity to activate and modulate AMPA and NMDA receptors. In this study, we aimed to investigate whether inhibition of proline transporters could enhance glutamatergic neurotransmission and potentially exhibit antipsychotic effects in an experimental schizophrenia model. Using molecular dynamics analysis in silico, we validated an innovative PROT inhibitor, LQFM215. We quantified the cytotoxicity of LQFM215 in the Lund human mesencephalic cell line (LUHMES). Subsequently, we employed the ketamine-induced psychosis model to evaluate the antipsychotic potential of the inhibitor, employing behavioral tests including open-field, three-chamber interaction, and prepulse inhibition (PPI). Our results demonstrate that LQFM215, at pharmacologically active concentrations, exhibited negligible neurotoxicity when astrocytes were co-cultured with neurons. In the ketamine-induced psychosis model, LQFM215 effectively reduced hyperlocomotion and enhanced social interaction in a three-chamber social approach task across all administered doses. Moreover, the compound successfully prevented the ketamine-induced disruption of sensorimotor gating in the PPI test at all tested doses. Overall, these findings suggest that PROT inhibition could serve as a potential therapeutic target for managing symptoms of schizophrenia model.

Ophthalmic artery resistance index after peribulbar block in the presence of epinephrine.

PURPOSE: There are controversies regarding ophthalmic artery (OA) flow after peribulbar block in the presence of epinephrine. Therefore, we aimed to evaluate OA flow via echo-Doppler before and after peribulbar block with lidocaine in the presence or absence of epinephrine. METHODS: Fifty-six patients who had an American Society of Anesthesiologists (ASA) classification of I, II or III and were eligible for cataract phacoemulsification surgery were selected. Patients with other eye diseases were excluded. Patients were divided into two groups: group 1-peribulbar block with lidocaine and 1/200,000 epinephrine; group 2-peribulbar block with lidocaine in the absence of epinephrine. The resistance index (RI), peak systolic velocity (PSV), end diastolic velocity (EDV) of the OA were evaluated using echo-Doppler before and 10 min after the peribulbar block. RESULTS: No differences between groups were observed in the RI before the peribulbar block as well regarding the presence of hypertension and the age or gender of the patient. After the peribulbar block, we observed a decrease in the RI in group 1 (p = 0.038, Cohen's d = 0.336) and no difference in the RI in group 2 (p = 0.109, Cohen's d = 0.172). When comparing group 1 and group 2, we observed a decrease in the RI in group 1 (p = 0.028, Cohen's d = 0,583). There was no difference between groups regarding the PSV and EDV after the peribulbar block. CONCLUSIONS: A decrease in RI was observed in the OA after peribulbar block with a vasoconstrictor, an effect that could be a benefit in some ocular surgeries.

Lipid dynamics in LPS-induced neuroinflammation by DESI-MS imaging.

It is well-established that bacterial lipopolysaccharides (LPS) can promote neuroinflammation through receptor Toll-like 4 activation and induces sickness behavior in mice. This phenomenon triggers changes in membranes lipid dynamics to promote the intracellular cell signaling. Desorption electrospray ionization mass spectrometry (DESI-MS) is a powerful technique that can be used to image the distribution of lipids in the brain tissue directly. In this work, we characterize the LPS-induced neuroinflammation and the lipid dynamics in C57BL/6 mice at 3 and 24 h after LPS injection. We have observed that intraperitoneal administration of LPS (5 mg/kg body weight) induces sickness behavior and triggers a peripheral and cerebral increase of pro- and anti-inflammatory cytokine levels after 3 h, but only IL-10 was upregulated after 24 h. Morphological analysis of hypothalamus, cortex and hippocampus demonstrated that microglial activation was present after 24 h of LPS injection, but not at 3 h. DESI-MS revealed a total of 14 lipids significantly altered after 3 and 24 h and as well as their neuroanatomical distribution. Multivariate statistical analyzes have shown that ions associated with phosphatidylethanolamine [PE(38:4)] and docosatetraenoic acid [FA (22:4)] could be used as biomarkers to distinguish samples from the control or LPS treated groups. Finally, our data demonstrated that monitoring cerebral lipids dynamics and its neuroanatomical distribution can be helpful to understand sickness behavior and microglial activation after LPS administration.

Choroid plexus cauterization on treatment of hydranencephaly and maximal hydrocephalus.

INTRODUCTION: The standard treatment for hydranencephaly and maximal hydrocephalus consists of inserting shunts, although complications frequently occur. Choroid plexus cauterization (CPC) is an alternative, but its long-term efficacy and the factors associated with the success and failure of controlling head circumference (HC) are not well defined. OBJECTIVE: This study aims to evaluate the long-term efficacy and factors related to the success rate of CPC in the treatment of hydranencephaly and maximal hydrocephalus. METHOD: Forty-two children with maximal hydrocephalus and hydranencephaly underwent CPC from 2006 to 2014 and were retrospectively evaluated. Children with less than 3 months of follow-up were excluded. The long-term efficacy and success rate of possible variables (i.e., sex, type of malformation, type of surgery performed, treatment hospital, age, and HC at the time of surgery and birth) were evaluated. RESULTS: Thirty-four children were considered for the effectiveness analysis. Treatment was successful in 24 children (70.6%), and failure occurred in 10 children (29.4%). Failure was detected soon after the endoscopic procedure (average 116 days). There was no difference in effectiveness when comparing the age at the moment of surgery (p = 0.473), type of malformation (p = 1), HC at birth (0.699), and HC at the time of surgery (p = 0.648). The surgical death rate was 7.14%. CONCLUSION: Endoscopic CPC was a valid procedure used to treat hydranencephaly and maximal hydrocephaly, and it was effective in 70.6% of cases, with an average follow-up period of 32 months. When failures occurred, they occurred early. None of the analyzed variables interfered with the success of the treatment.

Comparative presynaptic effects of the volatile anesthetics sevoflurane and isoflurane at the mouse neuromuscular junction.

INTRODUCTION: Sevoflurane and isoflurane are anesthetics that cause muscle relaxation and potentiate the effects of neuromuscular blocking agents. Their presynaptic mechanisms of action are not understood completely, especially at the motor nerve terminal. METHODS: We compared the presynaptic effects of these anesthetics on the exocytosis of synaptic vesicles labeled with the dye FM1-43 at the mouse neuromuscular junction. RESULTS: Neither anesthetic evoked spontaneous exocytosis of synaptic vesicles, but both significantly inhibited the depolarization evoked by 4-aminopyridine and veratridine, suggesting a putative action on sodium channels. Exocytosis evoked by veratridine was inhibited by tetrodotoxin alone or in conjunction with sevoflurane or isoflurane, indicating that both agents may target voltage-gated sodium channels. CONCLUSIONS: We suggest that sevoflurane and isoflurane inhibit exocytosis evoked by sodium-dependent depolarization and might act on tetrodotoxin-sensitive sodium channels. These findings contribute to a better understanding of some clinical neuromuscular effects induced by these anesthetics.

Effect of clonidine added to lidocaine for sub-Tenon's (episcleral) anesthesia in cataract surgery.

PURPOSE: We aimed to evaluate the duration of anesthesia, analgesia and ocular akinesia of clonidine added to lidocaine in sub-Tenon's anesthesia in patients undergoing cataract surgery. METHODS: Forty patients were prospectively enrolled. They were randomized to two sub-Tenon's anesthesia groups: group L (6 ml of lidocaine 2 %, 1 ml of 0.9 % saline and 25 UI/ml of hyaluronidase), and group C (6 ml lidocaine 2 %, clonidine 1 µg/kg, 1 ml of 0.9 % saline and 25 UI/ml of hyaluronidase). Duration of sensory anesthesia, ocular akinesia in all directions, akinesia of the levator palpebrae superioris and orbicularis oculi muscles, the duration of analgesia (time to the first postoperative use of analgesics), the overall use of analgesics and the presence of adverse effects were recorded . RESULTS: The duration of sensory anesthesia and akinesia of the four rectus, levator palpebrae superioris, and orbicularis oculi muscles was significantly longer in group C (p < 0.05). The number of patients who required analgesics was similar between the groups but the duration of analgesia was longer in group C (p < 0.05). No significant adverse effects were observed. CONCLUSION: The addition of clonidine 1 µg/kg to 2 % lidocaine in sub-Tenon's anesthesia for cataract surgery increased the duration of sensory anesthesia, ocular akinesia, and the duration of analgesia.

In silico evidence of bitopertin's broad interactions within the SLC6 transporter family.

The Glycine Transporter Type 1 (GlyT1) significantly impacts central nervous system functions, influencing glycinergic and glutamatergic neurotransmission. Bitopertin, the first GlyT1 inhibitor in clinical trials, was developed for schizophrenia treatment but showed limited efficacy. Despite this, bitopertin's repositioning could advance treating various pathologies. This study aims to understand bitopertin's mechanism of action using computational methods, exploring off-target effects, and providing a comprehensive pharmacological profile. Similarity Ensemble Approach (SEA) and SwissTargetPrediction initially predicted targets, followed by molecular modeling on SWISS-MODEL and GalaxyWeb servers. Binding sites were identified using PrankWeb, and molecular docking was performed with DockThor and GOLD software. Molecular dynamics analyses were conducted on the Visual Dynamics platform. Reverse screening on SEA and SwissTargetPrediction identified GlyT1 (SLC6A9), GlyT2 (SLC6A5), PROT (SLC6A7), and DAT (SLC6A3) as potential bitopertin targets. Homology modeling on SwissModel generated high-resolution models, optimized further on GalaxyWeb. PrankWeb identified similar binding sites in GlyT1, GlyT2, PROT, and DAT, indicating potential interaction. Docking studies suggested bitopertin's interaction with GlyT1 and proximity to GlyT2 and PROT. Molecular dynamics confirmed docking results, highlighting bitopertin's target stability beyond GlyT1. The study concludes that bitopertin potentially interacts with multiple SLC6 family targets, indicating a broader pharmacological property.

An evaluation of the antinociceptive effects of Phα1ß, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain.

Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1ß, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1ß reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1ß and MVIIA also inhibited capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of Phα1ß on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1ß, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1ß in the treatment of chronic pain.

Evaluation of functionality and socioeconomic status of patients with chronic pain.

OBJECTIVE: This study aimed to evaluate the influence of chronic pain on functionality and its consequences on work and patient income. METHODS: A total of 103 patients from the Multidisciplinary Pain Center of the Clinics Hospital of Universidade Federal de Minas Gerais were interviewed between January 2020 and June 2021, applying questionnaires on mobile devices. Socioeconomic data, multidimensional characterization of pain, and instruments for assessing pain functionality and intensity were analyzed. Pain intensity was categorized as mild, moderate, or intense for comparative analysis. Ordinal logistic regression was used to identify risk factors and variables that jointly influence the outcome of pain intensity. RESULTS: The patients had a median age of 55 years, were predominantly female, married or in a stable relationship, white race, and completed high school. The median family income was R$2,200. Most patients were retired due to disability and pain-related causes. Functionality analysis showed severe disability directly associated with pain intensity. The financial impacts observed were correlated with the pain intensity of the patients. Age was a risk factor for pain intensity, while sex, family income, and duration of pain served as protective factors. CONCLUSION: Chronic pain was associated with severe disability, decreased productivity, and exit from the labor market, with a negative impact on financial condition. Age, sex, family income, and duration of pain were directly associated with pain intensity.

Effect of intravenous anesthetic propofol on synaptic vesicle exocytosis at the frog neuromuscular junction.

AIM: To investigate the presynaptic effects of propofol, a short-acting intravenous anesthetic, in the frog neuromuscular junction. METHODS: Frog cutaneous pectoris nerve muscle preparations were prepared. A fluorescent tool (FM1-43) was used to visualize the effect of propofol on synaptic vesicle exocytosos in the frog neuromuscular junction. RESULTS: Low concentrations of propofol, ranging from 10 to 25 µmol/L, enhanced spontaneous vesicle exocytosis monitored by FM1-43 in a Ca(2+)-dependent and Na(+)-independent fashion. Higher concentrations of propofol (50, 100, and 200 µmol/L) had no effect on spontaneous exocytosis. By contrast, higher concentrations of propofol inhibited the Na(+)-dependent exocytosis evoked by 4-aminopyridine but did not affect the Na(+)-independent exocytosis evoked by KCl. This action was similar and non-additive with that observed by tetrodotoxin, a Na(+) channel blocker. CONCLUSION: Our data suggest that propofol has a dose-dependent presynaptic effect at the neuromuscular transmission which may help to understand some of the clinical effects of this agent on neuromuscular function.

Effect of adding clonidine to lidocaine on ocular hemodynamics during sub-Tenon's anesthesia: randomized double-blind study.

INTRODUCTION AND OBJECTIVES: Different regional anesthesia techniques for ophthalmology can have hemodynamic effects on the eye. We assessed the effects of adding clonidine to lidocaine on Intraocular Pressure (IOP), Ocular Pulse Amplitude (OPA), and Ocular Perfusion Pressure (OPP) after the sub-Tenon's technique for cataract surgery. METHODS: The study included 40 patients randomly allocated into two groups: sub-Tenon's blockade with Lidocaine plus Saline Solution (LS) or Lidocaine plus Clonidine (LC). IOP, OPA and OPP were measured before anesthesia, and 1, 5 and 10 minutes after the injection of anesthetic solution. RESULTS: There was no difference between the groups in IOP, OPA, and OPP baseline values. After the injection of the anesthetic solution, the IOP increased in both groups at minute one, with a mean difference of +4.67 mmHg (p = 0.001) and +2.15 mmHg (p = 0.013) at 5 minutes. The increase was lower in the LC group when compared to LS (p = 0.027). OPA decreased in both groups, with a baseline difference, after 1 minute, of -0.85 mmHg (p =  -0.85 mmHg (p = 0.001), and at 5 and 10 minutes with differences of -1.17 (p = 0.001) and -0.89 mmHg (p = 0.001), respectively. The highest decrease was observed in group LC in relation to group LS (p = 0.03). There was no difference in OPP in relation to baseline measurements. CONCLUSIONS: Adding clonidine to lidocaine for sub-Tenon's anesthesia reduced IOP and OPA without significant changes in OPP.

Residual neuromuscular blockade and late neuromuscular blockade at the post-anesthetic recovery unit: prospective cohort study.

INTRODUCTION AND OBJECTIVES: The use of neuromuscular blockers during surgery represented a landmark for anesthesiology. However, their use can prompt residual Neuromuscular Blockade (RNMB) and objective monitoring of neuromuscular function is crucial to warrant the recovery of muscle strength. The present study aimed to estimate the incidence of RNMB and late Neuromuscular Blockade (LNMB) at the Post-Anesthetic Recovery Unit (PACU). METHOD: The study included 85 patients, 43 of which received cisatracurium and 42 of which, rocuronium. The depth of the Neuromuscular Blockade (NMB) was assessed by Train Of Four (TOF). NMB reversal was performed with the administration of neostigmine and atropine.RNMB was defined when a patient presented TOF below 90% at the PACU. RESULTS: RNMB at the PACU was diagnosed in 39.5% and 40.5% of the patients receiving cisatracurium and rocuronium, respectively (p = 1.0). LNMB at the PACU was found in 32.6% and 16.7% of the patients receiving cisatracurium and rocuronium, respectively (p = 0.131). CONCLUSIONS: The incidence ofRNMB remains significant despite the use of intermediate-acting neuromuscular blockers and reversal agents. There was no statistically significant difference in the incidence of RNMB or LNMB in patients receiving cisatracurium or rocuronium. The use of objective NMB monitoring is effective for the diagnosis of RNMB, as well as for treatment management.

The Role of Astrocytes in the Neurorepair Process.

Astrocytes are highly specialized glial cells responsible for trophic and metabolic support of neurons. They are associated to ionic homeostasis, the regulation of cerebral blood flow and metabolism, the modulation of synaptic activity by capturing and recycle of neurotransmitters and maintenance of the blood-brain barrier. During injuries and infections, astrocytes act in cerebral defense through heterogeneous and progressive changes in their gene expression, morphology, proliferative capacity, and function, which is known as reactive astrocytes. Thus, reactive astrocytes release several signaling molecules that modulates and contributes to the defense against injuries and infection in the central nervous system. Therefore, deciphering the complex signaling pathways of reactive astrocytes after brain damage can contribute to the neuroinflammation control and reveal new molecular targets to stimulate neurorepair process. In this review, we present the current knowledge about the role of astrocytes in brain damage and repair, highlighting the cellular and molecular bases involved in synaptogenesis and neurogenesis. In addition, we present new approaches to modulate the astrocytic activity and potentiates the neurorepair process after brain damage.

Neurobiology of glycine transporters: From molecules to behavior.

Glycine transporters (GlyTs) are Na+/Cl--dependent neurotransmitter transporters, responsible for l-glycine uptake into the central nervous system. GlyTs are members of the solute carrier family 6 (SLC6) and comprise glycine transporter type 1 (SLC6A9; GlyT1) and glycine transporter type 2 (SLC6A5; Glyt2). GlyT1 and GlyT2 are expressed on both astrocytes and neurons, but their expression pattern in brain tissue is foremost related to neurotransmission. GlyT2 is markedly expressed in brainstem, spinal cord and cerebellum, where it is responsible for glycine uptake into glycinergic and GABAergic terminals. GlyT1 is abundant in neocortex, thalamus and hippocampus, where it is expressed in astrocytes, and involved in glutamatergic neurotransmission. Consequently, inhibition of GlyT1 transporters can modulate glutamatergic neurotransmission through NMDA receptors, suggesting an alternative therapeutic strategy. In this review, we focus on recent progress in the understanding of GlyTs role in brain function and in various diseases, such as epilepsy, hyperekplexia, neuropathic pain, drug addiction, schizophrenia and stroke, as well as in neurodegenerative disorders.

[Combination of clonidine-bupivacaine in caudal epidural anesthesia for hypospadias surgery in children: prospective, randomized, blind study]. / Associação clonidina­bupivacaína na anestesia peridural caudal para cirurgia de hipospádia em crianças: estudo prospectivo, randomizado, encoberto.

BACKGROUND AND OBJECTIVES: The combination of clonidine with local anesthetic administered for epidural anesthesia via caudal route seems to improve the quality of postoperative analgesia, but with conflicting results. This study compared the postoperative analgesia of three different doses of clonidine combined with bupivacaine in caudal epidural anesthesia in children undergoing hypospadias repair. METHODS: Eighty children aged 1 to 10 years, candidates for surgical repair of hypospadias, were randomly divided into four groups of 20 patients to receive general anesthesia combined with caudal epidural anesthesia with bupivacaine 0.165% alone or in combination with 1, 2 or 3µg.kg-1 of clonidine. The primary outcome was morphine consumption in the first 24hours postoperatively. Mean arterial pressure, heart rate, end-tidal concentration of sevoflurane, time to awakening, pain severity (FLACC scale), level of sedation (RAMSAY), duration of analgesia, and occurrence of adverse effects were also compared. RESULTS: Intraoperatively, there was no difference between groups regarding mean arterial pressure, heart rate, end-tidal concentration of sevoflurane, and time to awakening. Postoperative morphine consumption and pain severity were similar between groups, but the group receiving clonidine (3µg.kg-1) had lower heart rate and higher sedation level than the group receiving bupivacaine alone. CONCLUSIONS: The combination of clonidine at doses of 1, 2 or 3µg.kg-1 with bupivacaine 0.16% via caudal epidural route did not alter the consumption of morphine in the early postoperative period of children undergoing hypospadias repair.

Halothane induces vesicular and carrier-mediated release of [3H]serotonin from rat brain cortical slices.

The serotonergic system may play a role during general anesthesia but the effect of the volatile anesthetic halothane on the release of serotonin (5-HT) is not fully understood. Rat brain cortical slices were labeled with [3H]5-HT to investigate the effects of halothane on the release of this neurotransmitter from the central nervous system. Halothane induced an increase on the release of [3H]5-HT that was dependent on incubation time and anesthetic concentration (0.006, 0.012, 0.024, 0.036, 0.048 and 0.072 mM). This effect was independent of extracellular calcium and was not affected by tetrodotoxin (blocker of voltage dependent Na+ channels). In contrast, the halothane-evoked [3H]5-HT release was reduced by BAPTA-AM, a membrane-permeable BAPTA analog that chelates intracellular Ca2+. The anesthetic-induced [3H]5-HT release depends on the ryanodine-sensitive intracellular calcium store since it was blocked by dantrolene and azumolene (inhibitors of the calcium-release through ryanodine receptors) but was not affected by aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-triphosphate receptor. The [3H]5-HT release induced by halothane comes mainly from the vesicular pool since it was reduced in about 70% by reserpine, a blocker of vesicular monoamine transporter. The halothane-evoked release of [3H]5-HT release is reduced by fluoxetine, an inhibitor of 5-HT uptake, and the volatile agent also decreased the uptake of [3H]5-HT into rat brain cortical slices. Moreover, a decrease on halothane-induced release of [3H]5-HT was also observed when the brain cortical slices were incubated at low temperature, which is known to interfere with the carrier-mediated release of the neurotransmitter. Ouabain, a Na+/K+ ATPase pump inhibitor, which induces 5-HT release through reverse transport, also decreased [3H]5-HT release induced by halothane, confirming the involvement of a carrier-mediated release of the neurotransmitter in the presence of halothane. In conclusion, these data suggest that halothane induces vesicular and carrier-mediated release of [3H]5-HT in rat brain cortical slices.

Single-injection femoral nerve block with 0.25% ropivacaine or 0.25% bupivacaine for postoperative analgesia after total knee replacement or anterior cruciate ligament reconstruction.

STUDY OBJECTIVE: To investigate the effects of single-injection femoral nerve block (FNB) in postoperative pain after total knee replacement (TKR) and anterior cruciate ligament (ACL) reconstruction. DESIGN: Prospective, randomized, double-blind study. PATIENTS: 96 ASA physical status I, II, and III patients, scheduled for TKR or ACL reconstruction. INTERVENTIONS: All patients received a standard spinal anesthetic, then were randomly divided into three treatment groups as follows: Group B (n = 30) received an FNB with 40 mL of 0.25% bupivacaine containing epinephrine, 1:200,000; Group R (n = 32) received an FNB with 40 mL of 0.25% ropivacaine; and Group C (n = 28) received no FNB. MEASUREMENTS: The following clinical outcomes were assessed at up to 6 hours (T1), 6 to 10 hours (T2), and 10 to 24 hours (T3) after spinal anesthesia was given: visual analog scale (VAS) for pain, both at rest and on movement (no or mild pain, moderate pain, or severe pain); morphine use; sensory block in the femoral, obturator, and lateral femoral cutaneous nerve dermatomes; and motor block of the femoral and obturator nerves. MAIN RESULTS: Except for VAS during rest and on movement at time T3, there were more Group C patients who experienced moderate or severe pain than those who had no pain or mild pain, when compared with Groups R and B. Sensory block in the femoral and lateral femoral cutaneous nerve dermatomes did not differ between Groups R and B at any times. However, sensory block in the obturator nerve dermatome was lower in Group R than Group B only at T3. We observed a lower, significant use of morphine at T2 when comparing Groups R and B with Group C. No Group R patient and about 30% of Group B patients remained with motor block of femoral and obturator nerves at T3. Except for frequency of nausea, which was highest in Group C, the frequency of other side effects was similar among the three groups. CONCLUSIONS: Femoral nerve block using 0.25% ropivacaine or 0.25% bupivacaine is an effective method of postoperative analgesia after TKR and ACL reconstruction, particularly for the first 10 hours after spinal anesthesia.

Sleep disorders in patients with chronic pain: cross-sectional study / Distúrbios do sono em pacientes com dor crônica: estudo transversal

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic pain and its relationship with sleep disturbance are common conditions with great influence on the individual's quality of life. The simultaneous occurrence of these two entities results in greater suffering, reduced functionality and well-being. The objective of this research was to evaluate the influence of chronic pain on sleep and its impact on quality of life. METHODS: This is an observational, cross-sectional, individual, uncontrolled study carried out at the Multidisciplinary Pain Center of the Clinical Hospital of the Federal University of Minas Gerais (Hospital das Clínicas da Universidade Federal de Minas Gerais - HC-UFMG). The patients answered a semi-structured, face-to-face interview via the pain center's own computer system (avaliaDor®), using internet-connected mobile devices. Socioeconomic and pain data was collected, and then instruments were applied to assess pain intensity (Visual Numerical Scale - VNS), quality of life (Medical Outcomes Study 36 - Short Form Health Survey - SF-36), presence of psychiatric disturbances (Hospital Depression Anxiety Scale - HAD) and sleep (Mini Sleep Questionnaire - MSQ). RESULTS: One hundred and three patients participated in the study. Seventy two percent were women, the median age was 55 years, and the patients were predominantly married, white and with a low level of schooling. Of the entire study population 74.76% presented "severe difficulty" in sleeping, while 22.33% had "good quality" sleep. Regarding pain intensity, patients in the moderate and severe pain groups had a higher percentage of "severe difficulty" in sleeping, when compared to patients with mild pain. About the presence of anxiety and depression, it was observed lower scores on: "restless sleep", "tiredness for no apparent reason", "wakes up with a headache", "wakes up and goes back to sleep", "wakes up tired in the morning", and finally "wakes up and does not go back to sleep". The general data from the SF-36 points to a low quality of life for the patients in the present study and, based on the multivariate analysis, the items "SF-36-Pain and SF-36-Vitalidade" were shown to be protective factors for the presence of sleep disturbances. CONCLUSION: Sleep disorders in patients with chronic pain are common and show a worsening in quality of life. The frequency of this disturbance was higher in patients with anxiety and depression compared to patients without these psychiatric disorders. The early identification of sleep disturbances in individuals with chronic pain is necessary to improve well-being.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor crônica e os distúrbios do sono são condições comuns. A ocorrência simultânea dessas duas entidades resulta em maior sofrimento pessoal e redução do bem-estar e da funcionalidade. O objetivo desta pesquisa foi avaliar a influência da dor crônica no sono e o seu impacto na qualidade de vida. MÉTODOS: Trata-se de um estudo observacional, transversal, individual e não controlado, realizado no Centro Multidisciplinar de Dor do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Os pacientes responderam a uma entrevista semiestruturada, face a face, por meio do sistema de computador do próprio centro de dor (avaliaDor®), utilizando dispositivos móveis conectados à internet. Foram coletados dados socioeconômicos e de dor; em seguida foram aplicados instrumentos para avaliar a intensidade da dor (Escala Visual Numérica - EVN), a qualidade de vida (Medical Outcomes Study 36 - Short Form Health Survey - SF-36), a presença de distúrbios psiquiátricos (Escala Hospitalar de Ansiedade e Depressão - HAD) e o sono (Mini Sleep Questionnaire - MSQ). RESULTADOS Cento e três pacientes participaram do estudo. Setenta e dois por cento eram do sexo feminino, com mediana de idade de 55 anos, com predominância de brancos com baixo nível de escolaridade. De toda a população estudada, 74,76% dos participantes apresentaram "dificuldade grave" para dormir, enquanto 22,33% tiveram "boa qualidade" de sono. Em relação à intensidade da dor, os pacientes dos grupos de dor moderada e intensa apresentaram maior percentual de "dificuldade grave" para dormir quando comparados aos pacientes com dor leve. Em relação à presença de ansiedade e depressão, observou-se maior pontuação nos itens: "sono agitado", "cansaço sem motivo aparente", "acorda com dor de cabeça", "acorda e volta a dormir", "acorda cansado pela manhã" e, por fim, "acorda e não volta a dormir". Os dados gerais do SF-36 apontam para uma baixa qualidade de vida dos doentes do presente estudo e, com base na análise multivariada, os itens "SF-36-Dor e SF-36-Vitalidade" revelaram-se fatores protetores da presença de perturbações do sono. CONCLUSÃO: Os distúrbios de sono em pacientes com dor crônica são comuns e determinam piora na qualidade de vida. A frequência desse distúrbio foi maior nos pacientes com ansiedade e depressão, em comparação com os pacientes que não apresentaram essas desordens psiquiátricas. A identificação precoce dos distúrbios do sono, em indivíduos com dor crônica, é fundamental para alcançar maior bem-estar.

Evaluation of functionality and socioeconomic status of patients with chronic pain

SUMMARY OBJECTIVE: This study aimed to evaluate the influence of chronic pain on functionality and its consequences on work and patient income. METHODS: A total of 103 patients from the Multidisciplinary Pain Center of the Clinics Hospital of Universidade Federal de Minas Gerais were interviewed between January 2020 and June 2021, applying questionnaires on mobile devices. Socioeconomic data, multidimensional characterization of pain, and instruments for assessing pain functionality and intensity were analyzed. Pain intensity was categorized as mild, moderate, or intense for comparative analysis. Ordinal logistic regression was used to identify risk factors and variables that jointly influence the outcome of pain intensity. RESULTS: The patients had a median age of 55 years, were predominantly female, married or in a stable relationship, white race, and completed high school. The median family income was R$2,200. Most patients were retired due to disability and pain-related causes. Functionality analysis showed severe disability directly associated with pain intensity. The financial impacts observed were correlated with the pain intensity of the patients. Age was a risk factor for pain intensity, while sex, family income, and duration of pain served as protective factors. CONCLUSION: Chronic pain was associated with severe disability, decreased productivity, and exit from the labor market, with a negative impact on financial condition. Age, sex, family income, and duration of pain were directly associated with pain intensity.