Ultrasound-guided dexmedetomidine combination with modified high fascia iliaca compartment block for arthroscopic knee surgery: what is the optimal dose of dexmedetomidine?

BACKGROUND: Total knee arthroplasty (TKA) is a common orthopedic procedure for end-stage knee osteoarthritis. Although effective in relieving pain and improving function, postoperative pain is still a common and distressing problem for many patients. This study aims to investigate efficacy of combined administration of dexmedetomidine and modified high fascia iliaca compartment block (H-FICB) in managing acute and chronic pain after TKA, as well as to identify the optimal dosage of dexmedetomidine. METHODS: A double-blind, randomized controlled trial was conducted to evaluate the effects of dexmedetomidine in patients undergoing TKA. A total of 96 patients undergoing TKA were randomly assigned to one of three groups, were treated with different doses of dexmedetomidine All groups received H-FIB. Pain scores, opioid consumption, side effects, and quality of life were recorded 48 h postoperatively. RESULTS: The intraoperative consumption of remifentanil and propofol in Group Db was significantly reduced compared with that in Group D0 and Da (P < 0.05). Compared with D0 and Da group, Db group had the lowest number of rescue analgesia, analgesia time and morphine accumulative dosage 48 h after operation (P < 0.05). The Db group had the lowest scores on the numerical rating scale at rest (P < 0.05) and during movement (P < 0.01), followed by the Da group and then the D0 group. Additionally, the incidence of nausea and vomiting was significantly reduced in the Db group (P < 0.05). Furthermore, the Db group had the lowest incidence of chronic pain (P < 0.05). DISCUSSION: In comparison to the other two groups, the administration of combined dexmedetomidine and H-FIB resulted in a significant reduction in pain scores, opioid consumption, and side effects. The optimal dosage of dexmedetomidine was determined to be 1 µg/kg, which provided the most favorable pain relief with minimal adverse effects.

Effectiveness of antiseizure medications therapy in preventing seizures in brain injury patients: A network meta-analysis.

Purpose: To explore the effectiveness of different anti-seizure medications in preventing early and late post-traumatic epilepsy (PTE). The efficacy, treatment-related side-effects, and mortality of the different treatments were compared using a ranking model to identify the optimal treatment. Methods: A comprehensive literature search was performed using Pubmed, Medline, Embase, and Cochrane library databases. All relevant published articles up to 10 March 2022 were evaluated. The quality of the extracted data was assessed using either the Cochrane risk of bias tool or the Newcastle-Ottawa scale. The primary outcome measures were early or late post-traumatic seizures. The secondary outcome measures were mortality, treatment-related adverse effects, length of hospital stay, and length of stay within the intensive care unit (ICU). Results: A total of seven randomized controlled trials and 18 non-randomized controlled trials were included in this network meta-analysis. The trials included six interventions: Phenytoin (PHT)+phenobarbital (PB), levetiracetam (LEV), PHT, PHT-LEV, lacosamide (LCM), and valproate (VPA). All interventions except VPA significantly reduced the rate of early PTE in TBI patients compared with the placebo. Seven studies reported the impact of four treatments (PHT + PB, LEV, PHT, VPA) on late seizures and showed a significant reduction in the incidence of late seizures in patients with TBI compared with placebo. The impact of PHT, LEV, and VPA on mortality was reported in nine studies. PHT had no impact on mortality, but patients treated with both LEV and VPA had higher mortality than those treated with placebo. The treatment-related adverse effects of LEV, PHT, and LCM were reported in five studies. LEV and PHT had higher treatment-related adverse effects incidence than placebo, while LCM had no effect on treatment related-adverse effects. Conclusion: LEV and PHT prevented early and late PTE. PHT also reduced the mortality rate in patients with TBI. Both LEV and PHT had higher treatment-related adverse effects compared with placebo. However, LEV had a slightly lower incidence of treatment-related adverse effects when compared with PHT. Compared with PHT, LEV did not reduce the length of hospital stay but shortened the length of ICU stays. Therefore, based on the findings of this meta-analysis, we speculate that LEV is the best treatment option for TBI patients. However, further high-quality randomized controlled trials are required to confirm these findings.

Real-time ultrasound-guided stellate ganglion block for migraine: an observational study.

OBJECTIVE: To observe whether ultrasound-guided stellate ganglion block (SGB) can effectively relieve migraine pain and improve the quality of migraine patients' life. METHODS: 81 patients with migraines were enrolled in this study. The patients received SGB with 6 ml of 0.15% ropivacaine once every week for four times. Migraine was assessed with the Migraine Disability Assessment Scale (MIDAS) at baseline and three-months follow-up (Tm). The numerical rating scale (NRS) score at baseline, one day after treatment (Td) and Tm, the frequency of analgesic use in 3 months and the side effects were also recorded at the same time. RESULTS: The NRS score of migraine subjects decreased significantly from 7.0 (2.0) to 3.0 (1.0) at Td and 2.0 (2.0) at Tm (vs baseline, P < 0.01). The MIDAS total scores were 14.0 (10.5) at baseline and 7.0 (4.5) at Tm (P < 0.001). During the three months, the frequency of analgesic consumption was decreased from 6.2 ± 2.8 to 1.9 ± 1.8. There were no serious side effects. CONCLUSIONS: This study confirmed that ultrasound-guided SGB is an effective method to treat migraines. This technique can reduce pain and disability and then improve the quality of life of patients with migraines.

Cannabinoid receptor agonist WIN55212-2 reduces unpredictable mild stress-induced depressive behavior of rats.

BACKGROUND: Depression is a neurological disorder characterized by persistent low mood. A number of studies have suggested that the use of type 1 cannabinoid receptor (CB1R) agonists can reduce depressive behavior, but its effect on the depressive behavior and nerve damage of rats exposed to chronic unpredictable mild stress (CUMS) has not been reported. METHODS: Rats were exposed to CUMS for 4 weeks to induce depressive behavior. Male Sprague-Dawley (SD) rats aged 6-8 weeks were randomly divided into six groups: control group (control), depression group (CUMS), depression + fluoxetine group (Flu), depression + WIN55212-2 group (WIN), depression + NF-κB inhibitor group (PDTC), and depression + WIN + PDTC group (WIN + PDTC). We performed four behavioral experiments test to evaluate the depressive behaviors of rats. Hematoxylin and eosin (HE) and Nissl staining were performed to observe the neuron structures of the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Biochemical experiments were performed to evaluate the concentrations of nitric oxide (NO), malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). Fluorescence quantitative PCR was used to detect the mRNA expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and inducible nitric oxide synthase (iNOS) in the hippocampus, and western blot was performed to detect protein expression levels related to the NF-κB signaling pathway in the hippocampus. RESULTS: Compared with the normal control group, CUMS significantly induced abnormal behaviors in stressed rats. The concentrations of pro-inflammatory factors and oxidative stress injury factors in the hippocampus of the CUMS group increased significantly. The interventions of Flu, WIN, and PDTC significantly reduced neuroinflammation and oxidative stress injury. Compared with the WIN group, the WIN + PDTC intervention group had better results. In addition, WIN could significantly inhibit the activation of the NF-κB signaling pathway. CONCLUSIONS: This study showed that cannabinoid receptor agonists can reduce the CUMS-induced depressive behaviors of rats by blocking the NF-κB signaling pathway to alleviate neuroinflammation and oxidative stress injury.

Supplementation With Dexmedetomidine for Transsphenoidal Resection of Pituitary Adenoma: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The effect of dexmedetomidine supplementation on hemodynamic stability for transsphenoidal resection of pituitary adenoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexmedetomidine supplementation on hemodynamic stability for transsphenoidal resection of pituitary adenoma. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2020 for randomized controlled trials assessing the effect of dexmedetomidine supplementation on transsphenoidal resection of pituitary adenoma. RESULTS: Four randomized controlled trials involving 160 patients were included in the meta-analysis. Overall, compared with the control group for transsphenoidal resection of pituitary adenoma, dexmedetomidine supplementation resulted in significantly reduced mean arterial pressure at 30 minutes [mean difference (MD), -26.62; 95% confidence interval (CI), -36.71 to -16.53; P < 0.00001], heart rate at 30 minutes (MD, -16.50; 95% CI, -32.48 to -0.53; P = 0.04), blood loss (MD, -112.57; 95% CI, -165.12 to -60.01; P < 0.0001), and fentanyl (MD, -154.13; 95% CI, -303.97 to -4.29; P = 0.04), but demonstrated similar incidence of nausea and vomiting (odds ratio, 0.37; 95% CI, 0.13-1.03; P = 0.06), and hypotension (odds ratio, 2.11; 95% CI, 0.49-9.22; P = 0.32). CONCLUSIONS: Dexmedetomidine supplementation was effective in improving hemodynamic stability for transsphenoidal resection of pituitary adenoma.

Ultrasound-Guided Rectus Sheath Block Combined with Butorphanol for Single-Incision Laparoscopic Cholecystectomy: What is the Optimal Dose of Ropivacaine?

PURPOSE: In recent years, ultrasound-guided rectus sheath block (RSB) has been widely used in postoperative analgesia of abdominal operation. However, there is no uniform standard for the optimal dose of local anesthetics (LA) under ultrasound-guided rectus sheath block. This study aimed to determine the dose of ropivacaine combined with butorphanol that is effective in 50% (ED50) and 95% (ED95) of subjects for successful pain-free ultrasound-guided RSB in single-incision laparoscopic cholecystectomy (SILC). PATIENTS AND METHODS: Twenty-four patients scheduled to undergo single-incision laparoscopic cholecystectomy received an ultrasound-guided RSB. The initial dose of ropivacaine injected was 1.7 mg/kg, which was subsequently increased or decreased by 0.2 mg/kg, depending on whether the previous patient was free from pain (numeric rating scale (NRS) score of incisional pain at rest within 12 h after operation ≤ 3). All patients were treated with butorphanol 0.02 mg/kg as preemptive analgesia. The ED50 and ED95 were calculated using a probit regression model. RESULTS: The ED50 and ED95 of ropivacaine combined with butorphanol in ultrasound-guided rectus sheath block for analgesia in SILC, which were calculated by the probit regression model, were 0.719 mg/kg (95% confidence interval (CI), 0.553 mg/kg-0.873 mg/kg) and 0.967 mg/kg (95% CI, 0.835 mg/kg-1.91 mg/kg), respectively. CONCLUSION: As part of a multimodal analgesia strategy, a dose of 0.719 mg/kg ropivacaine provided successful RSB under ultrasound guidance in 50% of the patients who underwent SILC. A dose of 0.967 mg/kg would be successful in 95% of patients.

Perioperative Analgesic Effects of Preemptive Ultrasound-Guided Rectus Sheath Block Combined with Butorphanol or Sufentanil for Single-Incision Laparoscopic Cholecystectomy: A Prospective, Randomized, Clinical Trial.

PURPOSE: Pain after single-incision laparoscopic cholecystectomy (SILC), especially visceral pain, often troubles patients and doctors. Whether preemptive butorphanol can relieve visceral pain in patients undergoing SILC remains unknown. The goal of this study was to assess the efficacy of ultrasound-guided bilateral rectus sheath block (RSB) and butorphanol for perioperative analgesia in patients undergoing SILC. PATIENTS AND METHODS: Fifty-eight patients who met the criteria were randomly divided into two groups, both of which were given preemptive RSB. Patients were given either butorphanol 0.02mg/kg (group B, n=29) or sufentanil 0.1 µg/kg (group S, n=29) as preemptive analgesia. The primary outcome was the cumulative frequency of rescue analgesic request within 24 hours after operation. Secondary outcomes were numeric rating scale (NRS) scores (from 0 to 10) of incisional pain and visceral pain, the length of hospital stay and the incidence of postoperative adverse events. RESULTS: The frequency of postoperative rescue analgesic request of group S was significantly higher than that of group B (P=0.021). The NRS scores for visceral pain were lower in group B at 2, 6 and 12 hours after surgery than in group S (both P<0.001). The occurrence of postoperative nausea and vomiting (PONV) was significantly higher in group S. There were no significant differences between two groups for other outcomes. CONCLUSION: Butorphanol can provide sufficient visceral pain treatment after SILC than the dose of sufentanil in equal analgesic effect.

Protective effect of nicorandil on collapse­induced lung injury in rabbits by inhibiting apoptosis.

The one­lung ventilation (OLV) technique is vital in thoracic surgery. However, it can result in severe lung injury, which is difficult to manage. The main solution at present is the use of ventilation strategies, including continuous positive oxygen pressure, low tidal volume and high frequency ventilation, and the administering of drugs, including phenylephrine, dexmedetomidine and morphine. However, the protective effect of these methods on the lungs is not sufficient to improve the prognosis of patients. Therefore, how to develop a novel protective drug remains an open question. Nicorandil, a mitochondrial (mito)KATP­specific opener, serves an important role in cardioprotection, although its effect on lung injury remains unclear. The present study examined the protective role of nicorandil against collapse­induced lung injury in rabbits undergoing OLV. Changes in arterial oxygen saturation (SaO2), arterial partial pressure for oxygen (PaO2), wet/dry weight ratio, and the microstructure of tissues and cells were observed. Enzyme­linked immunosorbent assays were used to determine the concentrations of malondialdehyde (MDA) and tumor necrosis factor (TNF)­α, and the activity of superoxide dismutase (SOD) in rabbits treated with nicorandil. Terminal deoxynucleotidyl transferase transfer­mediated dUTP nick end­labeling was used to detect apoptosis and western blotting was used to analyze the relative proteins involved in apoptosis. Western blotting and reverse transcription­quantitative polymerase chain reaction analysis were used to examine the expression of hypoxia inducible factor 1α (HIF­1α), phosphatidylinositol­3­kinase (PI3K), protein kinase B (Akt) and nuclear factor (NF)­κB in the lungs of rabbits treated with nicorandil. The SaO2 and PaO2 in the high­dose group were significantly higher than those in the control group in the process of OLV. The wet/dry weight ratio, and the concentrations of MDA and TNF­α in the collapsed lung of the high­dose group were significantly lower than those in the control group. The activity of SOD in the high­dose group was significantly higher than that in the control group. The lung had improved microstructure and less apoptosis, which was determined by the Bax/Bcl2 ratio in the high­dose group. The expression levels of PI3K, phosphorylated Akt and HIF­1α were upregulated, whereas the expression of NF­κB was downregulated. In conclusion, nicorandil had a protective effect via inhibiting apoptosis in non­ventilated lung collapsed and re­expansion during OLV in the rabbit. It acted on mitoKATP through the PI3K/Akt signaling pathway.

Translocation Associated Membrane Protein 1 Contributes to Chronic Constriction Injury-Induced Neuropathic Pain in the Dorsal Root Ganglion and Spinal Cord in Rats.

Neuropathic pain is a severe debilitating state caused by injury or dysfunction of somatosensory nervous system, and the clinical treatment is still challenging. Translocation associated membrane protein 1 (TRAM1), an adapter protein, participates in a variety of transduction pathways and mediates the biological functions such as cell proliferation, activation, and differentiation. However, whether TRAM1 is involved in the pathogenesis of neuropathic pain is still unclear. In our study, we reported the role of TRAM1 in the maintenance of neuropathic pain induced by chronic constriction injury (CCI) on rats. By western blot and staining, we found that TRAM1 increased in the dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons after CCI. Being similar to IB4-, CGRP-positive expressed area, TRAM1 also expressed in the superficial laminae of the spinal cord dorsal horn (SCDH), suggesting it was related to the innervations of the primary afferents. Moreover, intrathecal injection of TRAM1 siRNA or Toll-like receptor 4 (TLR4) inhibitor induced low expression of TRAM1 in SC, which alleviated the pain response induced by CCI. The upregulation of p-NF-κB expression was reversed by TRAM1 siRNA in SC and DRG, and intrathecal injection of p-NF-κB inhibitor relieved neuropathic pain. All the data indicated that TRAM1 could take part in CCI-induced pain and might be a potential treatment for chronic neuropathic pain.

Dynamic changes in hippocampal microglia contribute to depressive-like behavior induced by early social isolation.

Depression triggered by early-life stress has begun to attract wide attention due to its severe symptoms and poor treatment outcomes. However, the pathophysiological mechanism for this type of depression remains unclear. Recently, we and others reported that different types of chronic stress induce a significant loss of hippocampal microglia, which is mediated by an initial activation of these microglia. Since early-life stress also promotes microglial activation, we investigated the dynamic changes in hippocampal microglia in mice suffering from depression induced by early social isolation (ESI). Results showed that 8 days of ESI induced depressive-like behaviors in a tail suspension test, forced swim test, sucrose preference test, and open field test, and it also induced a loss and dystrophy of hippocampal microglia. We found that this ESI-induced loss of hippocampal microglia was mediated by both microglial activation and apoptosis. This was demonstrated by the following results: (i) 1 day of ESI induced an obvious activation of hippocampal microglia followed by their apoptosis, and (ii) the blockade of the initial activation of hippocampal microglia by minocycline pretreatment suppressed the ESI-induced apoptosis and loss as well as ESI-induced depressive-like behavior. Lipopolysaccharide (LPS) and macrophage colony-stimulating factor (M-CSF), two activators of microglia, almost completely reversed ESI-induced depressive-like behavior by promoting microglial proliferation in the hippocampus. These results reveal an etiological role of hippocampal microglial loss in ESI-induced depression and demonstrate that the restoration of microglial homeostasis in the hippocampus may serve as a therapeutic strategy for depression induced by early-life stress.

PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in rat spinal cord.

BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis. Cellular location of PKM2 was examined by immunofluorescence. Knockdown of PKM2 was achieved by intrathecal injection of specific small interfering RNA (siRNA). Von Frey filaments and radiant heat tests were performed to determine mechanical allodynia and thermal hyperalgesia respectively. Lactate and adenosine triphosphate (ATP) contents were measured by specific kits. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels were detected by ELISA kits. RESULTS: CCI markedly increased PKM2 level in rat spinal cord. Double immunofluorescent staining showed that PKM2 co-localized with neuron, astrocyte, and microglia. Intrathecal injection of PKM2 siRNA not only attenuated CCI-induced ERK and STAT3 activation, but also attenuated mechanical allodynia and thermal hyperalgesia induced by CCI. However, PKM2 siRNA failed to inhibit the activation of AKT. In addition, PKM2 siRNA significantly suppressed the production of lactate and pro-inflammatory mediators. CONCLUSION: Our findings demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced neuropathic pain and inflammatory responses in rats, possibly through regulating ERK and STAT3 signaling pathway.

Fascin-1 Contributes to Neuropathic Pain by Promoting Inflammation in Rat Spinal Cord.

Neuropathic pain is a complicated clinical syndrome caused by heterogeneous etiology. Despite the fact that the underlying mechanisms remain elusive, it is well accepted that neuroinflammation plays a critical role in the development of neuropathic pain. Fascin-1, an actin-bundling protein, has been proved to be involved in the processing of diverse biological events including cellular development, immunity, and tumor invasion etc. Recent studies have shown that Fascin-1 participates in antigen presentation and the regulation of pro-inflammatory agents. However, whether Fascin-1 is involved in neuropathic pain has not been reported. In the present study we examined the potential role of Fascin-1 by using a rodent model of chronic constriction injury (CCI). Our results showed that Fascin-1 increased rapidly in dorsal root ganglions (DRG) and spinal cord (SC) after CCI. The increased Fascin-1 widely expressed in DRG, however, it localized predominantly in microglia, seldom in neuron, and hardly in astrocyte in the SC. Intrathecal injection of Fascin-1 siRNA not only suppressed the activation of microglia and the release of pro-inflammatory mediators, but also attenuated the mechanical allodynia and thermal hyperalgesia induced by CCI.

JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury.

Neuropathic pain, caused by a lesion or dysfunction of the somatosensory nervous system, is a severe debilitating condition with which clinical treatment remains challenging. Jun activation domain-binding protein (JAB1) is a multifunctional protein that participates in several signaling pathways, controlling cell proliferation and apoptosis. However, the expression and possible function of JAB1 in the pathogenesis of neuropathic pain has not been elucidated. This study aimed to investigate the possible involvement of JAB1. Here, employing a neuropathic pain model induced by chronic constriction injury (CCI) on rats, we reported the role of JAB1 in the maintenance of neuropathic pain. By western blot, we found that CCI markedly up-regulated JAB1 expression in the dorsal root ganglion (DRG) and spinal cord. Immunofluorescent assay demonstrated that JAB1 was extensively localized in IB4-, CGRP- and NF200-positive neurons in the injured L5 DRG, and mainly co-localized with NeuN in spinal cord. In addition, we showed that CCI induced phosphorylation of p65 and JNK in vivo. Intrathecal injection of JAB1 siRNA significantly attenuated the CCI-induced JNK and p65 phosphorylation and alleviated both mechanical allodynia and heat hyperalgesia in rats. Taken together, these results suggested that JAB1 promotes neuropathic pain via positively regulating JNK and NF-κB activation.