Efficacy of Intravenous Lidocaine for Pain Relief in the Emergency Department: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the efficacy of intravenous (IV) lidocaine with standard analgesics (NSAIDS, opioids) for pain control due to any cause in the emergency department. METHODS: The electronic databases of PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar were explored from 1st January 2000 to 30th March 2021 and randomized controlled trials (RCTs) comparing IV lidocaine with a control group of standard analgesics were included. RESULTS: Twelve RCTs including 1,351 patients were included. The cause of pain included abdominal pain, renal or biliary colic, traumatic pain, radicular low back pain, critical limb ischemia, migraine, tension-type headache, and pain of unknown origin. On pooled analysis, we found no statistically significant difference in pain scores between IV lidocaine and control group at 15 min (MD: -0.24 95% CI: -1.08, 0.61 I 2 = 81% p = 0.59), 30 min (MD: -0.24 95% CI: -1.03, 0.55 I 2 = 86% p = 0.55), 45 min (MD: 0.31 95% CI: -0.66, 1.29 I 2 = 66% p = 0.53), and 60 min (MD: 0.59 95% CI: -0.26, 1.44 I 2 = 75% p = 0.18). There was no statistically significant difference in the need for rescue analgesics between the two groups (OR: 1.45 95% CI: 0.82, 2.56 I 2 = 41% p = 0.20), but on subgroup analysis, the need for rescue analgesics was significantly higher with IV lidocaine in studies on abdominal pain but not for musculoskeletal pain. On meta-analysis, there was no statistically significant difference in the incidence of side-effects between the two study groups (OR: 1.09 95% CI: 0.59, 2.02 I 2 = 48% p = 0.78). CONCLUSION: IV lidocaine can be considered as an alternative analgesic for pain control in the ED. However, its efficacy may not be higher than standard analgesics. Further RCTs with a large sample size are needed to corroborate the current conclusions.

Increased cerebrospinal fluid neurofilament light chain in central nervous system inflammatory demyelinating disease.

BACKGROUND: Central nervous system (CNS) inflammatory demyelinating disease (IDD) is an immune-mediated disease that is pathologically characterized by demyelination and inflammatory infiltration in the CNS and includes clinically isolated syndrome (CIS), multiple sclerosis (MS), and neuromyelitis optica spectrum disorders (NMOSD). IDD is usually characterized by variable symptoms, multivariate imaging, uncertain reactions to treatment, and a variable prognosis, which makes it difficult to diagnose early. In recent years, the role of the neurofilament light chain (NFL), an axonal injury biomarker, in IDD has become increasingly important. We will detect and analyse cerebrospinal fluid (CSF) NFL levels in IDD and normal control patients to determine the significance of NFL in the diagnosis and prognostic prediction of IDD. METHODS: A total of 41 CIS, 34 MS and 73 NMOSD patients and 40 other patients with conditions such as neurosis and migraine with lumbar puncture were enrolled as the patient groups and the normal control (NC) group from the population of in- and outpatients of the Department of Neurology of the Sixth Medical Centre of Chinese People's Liberation Army General Hospital from January 2014 to October 2016. Clinical and neuroimaging features of the patient groups as well as CSF samples from both types of groups were collected, and the NFL levels of CSF were measured by enzyme linked immunosorbent assay. RESULTS: CSF NFL levels in the CIS, MS and NMOSD groups were significantly higher than those in the NC group (P < 0.05, analysis of variance of NFL levels was performed after logarithmic transformation based on 10). There were no statistically significant differences in the CSF NFL levels among the CIS, MS and NMOSD groups (P > 0.05). The NFL levels of CSF in the CIS, MS and NMOSD groups were correlated with the expanded disability status scale score and enhancement in gadolinium-magnetic resonance imaging (all P < 0.05). Gender, oligoclonal band in CSF, aquaporin 4 antibody and 25­hydroxy vitamin D3 [25(OH)D3] in serum were not related to the NFL levels (P > 0.05). CONCLUSION: The NFL level of CSF is conducive to assessing the severity and probable progress of IDD but is not helpful in distinguishing IDD among Chinese.

PGC-1α or FNDC5 Is Involved in Modulating the Effects of Aß1-42 Oligomers on Suppressing the Expression of BDNF, a Beneficial Factor for Inhibiting Neuronal Apoptosis, Aß Deposition and Cognitive Decline of APP/PS1 Tg Mice.

Alzheimer's disease (AD) is generally defined as the aberrant production of ß-amyloid protein (Aß) and hyperphosphorylated tau protein, which are deposited in ß-amyloid plaques (APs) and neurofibrillary tangles (NFTs), respectively. Decreased levels of brain-derived neurotrophic factor (BDNF) have been detected in patients with AD compared to control subjects. However, the underlying molecular mechanisms driving the downregulation of the BDNF remain unknown. Therefore, we explored the mechanisms underlying the regulation of BDNF in the neurons of APP/PS1 transgenic (Tg) mice, an AD experimental model. Using the APP/PS1 Tg mice, we found that BDNF expression was markedly downregualted at the age of 3- and 9-month-old. After cerebroventricular injection (i.c.v) of Aß1-42 oligomers into the mice, BDNF was also found to be decreased, which demonstrated the critical roles of the Aß1-42 oligomers in regulating the expression of BDNF. In neuronal culture, peroxisome proliferators-activated receptor γ coactivator 1α (PGC-1α) and fibronectin type III domain-containing 5 (FNDC5) were found to be downregulated by treatment with the Aß1-42 oligomers. In addition, overexpression of either PGC-1α or FNDC5 reversed the suppressive effects of the Aß1-42 oligomers on the expression of BDNF in neuroblastoma 2a (n2a) cells. More importantly, elevating the levels of PGC-1α, FNDC5 or BDNF in the n2a cells counteracted the effects of the Aß1-42 oligomers on neuronal apoptosis. Additionally, intranasal administration BDNF in the APP/PS1 Tg mice decreased the Aß deposition and reduced the cognitive decline of the mice.