Altered Cortical Reorganization and Brain Functional Connectivity in Phantom Limb Pain: A Functional MRI Study.

OBJECTIVES: Functional neuroimaging studies have shown that amputees have altered cortical reorganization and functional connectivity (FC). This study aimed to investigate whether patients with phantom limb pain (PLP) and PLP-free lower limb amputees exhibit changes in corresponding primary cortical motor area/somatosensory cortex (M1/S1) cortical reorganization and supplementary motor area (SMA) network FC. The association between functional magnetic resonance imaging (fMRI) changes and clinical parameters is also explored. METHODS: A total of 10 PLP patients were matched with 10 PLP-free amputees and 10 healthy controls (HCs). Before undergoing fMRI, all participants completed questionnaires evaluating pain, anxiety, depression, and health-related quality of life. Task-related activation and regions of interest (ROI)-wise connectivity analysis were applied to differentiate the brain regions of amputees from those of HCs. Linear correlation analysis was used to evaluate the correlation between altered FC and clinical manifestations. RESULTS: As compared with HCs, PLP patients showed increased cortical activation in M1/S1 when moving the intact foot, imagining phantom big toe movement, or having the corresponding thumb stimulated. The increased FC in the SMA network included the SMA-caudate nucleus, SMA-bilateral insula, and SMA-anterior cingulate cortex. Furthermore, results of the linear correlation analysis demonstrated that this increased FC was positively correlated with VAS scores, negatively correlated with Medical Outcomes Study 36-item Short-Form (SF-36) scores, and not correlated with anxiety or depression scores. CONCLUSIONS: Phantom limb pain in lower limb amputees is associated with M1/S1 cortical reorganization and altered SMA network FC in different areas of the brain, which could help to support our understanding of the central mechanism of PLP.

Effect of Pharmacological Inhibition of Fat-Mass and Obesity-Associated Protein on Nerve Trauma-Induced Pain Hypersensitivities.

Genetic knockout or knockdown of fat-mass and obesity-associated protein (FTO), a demethylase that participates in RNA N6-methyladenosine modification in injured dorsal root ganglion (DRG), has been demonstrated to alleviate nerve trauma-induced nociceptive hypersensitivities. However, these genetic strategies are still impractical in clinical neuropathic pain management. The present study sought to examine the effect of intrathecal administration of two specific FTO inhibitors, meclofenamic acid (MA) and N-CDPCB, on the development and maintenance of nociceptive hypersensitivities caused by unilateral L5 spinal nerve ligation (SNL) in rats. Intrathecal injection of either MA or N-CDPCB diminished dose-dependently the SNL-induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and spontaneous ongoing nociceptive responses in both development and maintenance periods, without altering acute/basal pain and locomotor function. Intrathecal MA also reduced the SNL-induced neuronal and astrocyte hyperactivities in the ipsilateral L5 dorsal horn. Mechanistically, intrathecal injection of these two inhibitors blocked the SNL-induced increase in the histone methyltransferase G9a expression and rescued the G9a-controlled downregulation of mu opioid receptor and Kv1.2 proteins in the ipsilateral L5 DRG. These findings further indicate the role of DRG FTO in neuropathic pain and suggest potential clinical application of the FTO inhibitors for management of this disorder.

Nerve trauma-caused downregulation of opioid receptors in primary afferent neurons: Molecular mechanisms and potential managements.

Neuropathic pain is the most common clinical disorder destroying the quality of patient life and leading to a marked economic and social burden. Opioids are still last option for pharmacological treatment of this disorder, but their antinociceptive effects are limited in part due to the downregulation of opioid receptors in the primary afferent neurons after peripheral nerve trauma. How this downregulation occurs is not completely understood, but recent studies have demonstrated that peripheral nerve trauma drives the alterations in epigenetic modifications (including DNA methylation, histone methylation and mciroRNAs), expression of transcription factors, post-transcriptional modifications (e.g., RNA methylation) and protein translation initiation in the neurons of nerve trauma-related dorsal root ganglion (DRG) and that these alternations may be associated with nerve trauma-caused downregulation of DRG opioid receptors. This review presents how opioid receptors are downregulated in the DRG after peripheral nerve trauma, specifically focusing on distinct molecular mechanisms underlying transcriptional and translational processes. This review also discusses how this downregulation contributes to the induction and maintenance of neuropathic pain. A deeper understanding of these molecular mechanisms likely provides a novel avenue for prevention and/or treatment of neuropathic pain.

The Trend of Labor Analgesia in the World and China: A Bibliometric Analysis of Publications in Recent 30 Years.

PURPOSE: Labor analgesia is part of the most important tasks an anesthesiologist needs to deal with. With the "two-child policy" in China, the number of parturients has increased significantly, labor analgesia more should be valued. There has been a tremendous change on labor analgesia research in China and around the world; however, broader trends in the prevalence and scope of labor analgesia research remain underexplored. The current study quantitatively analyzes trends in labor analgesia research publications in the past 30 years. METHODS: A bibliometric approach was used to search Scopus, PubMed, Web of Science and the China National Knowledge Infrastructure for all labor analgesia-related research articles. The research progress and growing trend were quantitatively analyzed by total publications, research types, research institutions, journal impact factors, and author's contribution. Total citations frequency, average citations per item and h-index were used for evaluating literature quantity. RESULTS: From 1988 to 2018, over 8000 documents in labor analgesia research field were published worldwide. According to Scopus, 68.2% papers of all documents were articles. The USA published the largest number of articles (2204, 27.45%). China had published 175 articles (2.18%), ranking the 11th. According to WOS, there were 221 research categories for labor analgesia articles all over the world. The total citations were 76,207, average 9.086 citations per item, and the h-index was 114, average 14 citations per item worldwide. The total citations and h-index of papers published in China were as follows: 353 total citations, 7.06 citations per item, and 10 h-index. High contribution journals, authors, institutions and the top 10 most cited articles on labor analgesia in the world and China were also listed. CONCLUSION: Labor analgesia research has grown markedly during the 1988-2018 period. Although China had made remarkable achievements, there was a gap in the high-quality studies between China and other leading countries.

Ultrasound for predicting difficult airway in obstetric anesthesia: Protocol and methods for a prospective observational clinical study.

BACKGROUND: Failed intubation and ventilation during cesarean deliveries are important causes of anesthetic-related maternal mortality. Due to the physiological changes in airway anatomy, parturient had higher incidences of difficult airway than non-obstetric population. Accurate airway assessment is the first step and the most important in airway management. However, the common clinical screening tests, shown low sensitivity and specificity with a limited predictive value. Ultrasound is a quick, noninvasive, inexpensive tool, with the advancement of ultrasound technology, modern ultrasound machine is more portable with better resolution and enhanced tissue penetration, provide better imaging in tissues like epiglottis, vocal cords, ring-shaped membrane, and can be used in airway assessment. Here, the aim of the current study was to find whether preoperative ultrasound assessment of neck anatomy can predict difficult airway in parturient, and provide new ideas and a theoretical basis in the airway management of obstetric anesthesia. METHODS: This is a prospective, observational single-blinded study in a single-center. Subjects will be recruited from patients aged from 18 to 60 years, gestational age ≥ 36 weeks, scheduled for cesarean section under general anesthesia and tracheal intubation. Ultrasound measurement will be performed to detect anterior cervical soft tissue thickness at five anatomical levels (hyoid bone, epiglottis, cricothyroid membrane, thyroid isthmus and suprasternal notch) in the upper airway. The thickness of the soft tissue in the front of the neck and clinical airway measurements will be compared between the "easy intubation" and "difficult intubation" group divided by Cormack-Lehane grade. Receiver-operating characteristic curves were used to determine the sensitivity and specificity of "difficulty prediction capability" of each sonographic and physical measurements. Clinical factors associated with difficult intubation will be determined by univariate analyses. Multiple logistic regression analysis performed to determine independent predictors of difficult intubation. CONCLUSIONS: The study outlined in this protocol will explore the possibility of ultrasound for predicting difficult airway in obstetric anesthesia. This may provide new insight into the practice of airway management. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800018949.