Activation of TREK1 Channel in the Anterior Cingulate Cortex Improves Neuropathic Pain in a Rat Model.

Objective. To explore the biological function and mechanism of TREK1 in neuropathic pain. Thirty-two healthy rats and rats with sciatic nerve chronic press-fitting model (chronic constriction injury of the sciatic nerve, CCI) were selected. Western blot, immunofluorescence staining, and patch clamp technique were performed to explore the biological functions of TREK1. The expression of TREK1 was decreased in the CCI model. The TREK1 channel current in the CCI model was decreased. After local administration of TREK1 channel activator in the anterior cingulate cortex area, the pain behavior of CCI rats and the expression of TREK1 protein were reversed. The expression of TREK1 was downregulated in the ACC area of CCI rats and the current of TREK1 was decreased, which played an important role in the regulation of neuropathic pain.

Effect of scalp nerve block with ropivacaine on postoperative pain in pediatric patients undergoing craniotomy: A randomized controlled trial.

Background: Scalp nerve block (SNB) is widely used for postoperative pain control, intraoperative hemodynamic control, and opioid-sparing in adult craniotomies. However, there are few studies of SNB in pediatric patients undergoing craniotomy. In the present study, we aimed to investigate the effect of SNB on postoperative pain, intraoperative hemodynamic stability, and narcotic consumption in pediatric craniotomy under general anesthesia. Methods: This trial is a single-center, prospective, randomized, and double-blind study. A total of 50 children aged between 2 and 12 years who are undergoing elective brain tumor surgery will be randomly allocated in a 1:1 ratio to receive either 0.2% ropivacaine for SNB (group SNB, intervention group, n = 25) or the same volume of saline (group Ctrl, control group, n = 25). The primary outcome was to assess the score of postoperative pain intensity at time 1, 4, 8, 12, 24, and 48 h postoperatively using the FLACC score method. Secondary outcomes were to record intraoperative hemodynamic variables (MAP and HR) during skull-pin fixation, skin incision and end of skin closure, intraoperative total consumption of remifentanil and propofol, postoperative opioid consumption, and the incidence of postoperative nausea and vomiting. Results: Fifty patients were analyzed (n = 25 in SNB group; n = 25 in control group). Compared to the control group, postoperative pain intensity was significantly relieved in the SNB group up to 8 h post-operatively. In addition, SNB provided good intraoperative hemodynamic stability, reduced intraoperative overall propofol and remifentanil consumption rate, and postoperative fentanyl consumption compared to the control group. However, the incidence of postoperative nausea and vomiting was not different between SNB and the control group. Conclusions: In pediatric craniotomies, SNB with 0.2% ropivacaine provides adequate postoperative pain control and good intraoperative hemodynamic stability during noxious events compared to the control group. Clinical trial registration: Chinese Clinical Trial Registry [No: ChiCTR2100050594], Prospective registration.

Structural and functional characterizations and heterogenous expression of the antimicrobial peptides, Hidefensins, from black soldier fly, Hermetia illucens (L.).

Insect defensins are effector components of the innate defense system. Defensins, which are widely distributed among insects, are a type of small cysteine-rich plant antimicrobial peptides with broad-spectrum antimicrobial activity. Here, the cDNAs of the black soldier fly, Hermetia illucens (L.), encoding six defensins, designated herein as Hidefensin1-1, 2, 3, 4, 5, 6. Moreover, Hidefensin1-1, 2, and 5 were identified for the first time by genome-targeted analysis. These Hidefensins were found to mainly adopt α-helix and ß-sheet conformation homology as modeled by PRABI, Swiss-Model and ProFunc server. Six conserved cysteine residues that contribute to three disulfide bonds formed the spacing pattern "C-X12-C-X3-C-X9-C-X5-C-X-C", which play a vital role in the molecular stability of Hidefensins. Phylogenetic analysis revealed that the homology of five Hidefensins (except Hidefensin4) was about 59%-92% compared with other insect defensins, indicating that they are novel antimicrobial peptides genes in black soldier fly. Furthermore, the Hidefensin1-1 was expressed in the Escherichia coli strain BL21(DE3) as a fusion protein with thioredoxin. Results showed that the purified TRX-Hidefensin1-1 exerted strong inhibitory effects against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli. The inhibitory efficacy of TRX-Hidefensin1-1 against Gram-positive bacteria was better than that against Gram-negative bacteria. These results indicated that Hidefensin1-1 has potent antimicrobial activities against test pathogens.

Upregulation of ubiquitin conjugating enzyme E2B (Ube2b) ameliorates neuropathic pain by regulating Kcna2 (potassium voltage-gated channel subfamily A member 2) in primary afferent neurons.

Neuropathic pain is a kind of pain caused by damage to somatosensory nervous system. Currently, neuropathic pain is still a medical problem for clinicians. Ubiquitin conjugating enzyme E2B (Ube2b) is validated to be implicated with nerve function, but whether Ube2b can play a role in neuropathic pain is still elusive. In this work, we constructed chronic constriction injury (CCI) rat model by ligating the left sciatic nerve, Ube2b protein expression was confirmed to be decreased in spinal cord tissues of CCI rats via Western blot analysis and immunofluorescence (IF) staining. Moreover, Ube2b elevation alleviated the thermal hyperalgesia and mechanical hyperalgesia in CCI rats according to paw withdrawal thermal latency (PWTL) and paw withdrawal mechanic threshold (PWMT). In addition, Hematoxylin-eosin staining revealed that Ube2b elevation suppressed chronic sciatic nerve injury. All these data suggested that Ube2b could ameliorate neuropathic pain in CCI rats. Mechanically, Ube2b upregulation elevated the protein level of Kcna2 (potassium voltage-gated channel subfamily A member 2) and decreased the protein level of DNMT3a (DNA methyltransferase 3 alpha). Ube2b elevation could increase Kcna2 expression via suppressing DNMT3a. Rescue assays unveiled that Ube2b overexpression modulated-mechanical hyperalgesia and thermal hyperalgesia were reversed by Kcna2 depletion, indicating that Ube2b alleviated neuropathic pain via mediating Kcna2 via the regulation of DNMT3a. In summary, we found that Ube2b elevation ameliorated neuropathic pain through regulating Kcna2, which might offer a novel biomarker for the therapies of neuropathic pain.

Long-duration general anesthesia influences the intelligence of school age children.

BACKGROUND: General anesthesia has been linked to impaired brain development in immature animals and young children. In this study the influence of orthopedic surgery under general anesthesia on the intelligence of school age children has been evaluated. METHODS: A total of 209 subjects aged 6-12 years were recruited and allocated into 4 groups according to the duration of general anesthesia, including a control group (n = 30), short (< 1 h, n = 49), moderate- (1-3 h, n = 51) and long-duration groups (> 3 h, n = 79), respectively. The intelligence quotient (IQ) of the subjects was measured by the Raven's Standard Progressive Matrices (RSPM) before and after orthopedic surgery under general anesthesia of various durations (vide supra). RESULTS: The IQ score decreased significantly in the long-duration group at 1 month post-operation compared with the pre-operation score (P < 0.001), and IQ did not recover completely at 3 months postoperatively (P < 0.05), but had recovered when measured at the 1-year follow-up. Moreover, this study showed that the development of children's intelligence was affected by the exposure time to anesthetics at a younger age (OR = 5.26, 95% CI:2.70-8.41, P < 0.001), having a mother with a low education level (OR = 2.71, 95% CI:1.24-6.14, P = 0.014) and premature birth (OR = 2.76, 95% CI:1.34-5.46, P = 0.005). CONCLUSIONS: More than 3 h general anesthesia influenced the IQ of school age children for up to 3 months after orthopedic surgery. Beside extended exposure time to anesthetics additional factors for post-operative IQ reduction were younger children age, mothers with low educational levels and premature birth. TRIAL REGISTRATION: Chinese Clinical Trial Registry with registration number ChiCTR-OOC-17013497  retrospectively registered on 11/23/2017.

Effects of colloid pre-loading on thromboelastography during elective intracranial tumor surgery in pediatric patients: hydroxyethyl starch 130/0.4 versus 5% human albumin.

BACKGROUND: Volume replacement therapy with colloid is still worth studying in major pediatric surgery with potential risk of bleeding. This study assessed the effects of 6% hydroxyethyl starch (HES) 130/0.4 and 5% Human Albumin (HA) on coagulation tested by thromboelastography (TEG) during elective intracranial tumor surgery in pediatric patients. METHODS: In this randomized controlled trial, 60 patients undergoing intracranial tumor resection under general anesthesia were assigned to HES and HA groups (n = 30), and administered preloads of 20 mL · kg-1 HES 130/0.4 and 5% HA, respectively, prior to dura opening. Primary outcomes were perioperative thromboelastography findings, and hemodynamic and hematological parameters. Blood transfusion, perioperative fluid balance, intracranial pressure, mortality, intensive care unit stay, and hospital stay were also assessed. RESULTS: TEG parameters did not differ after preloading compared to baseline values in either group, except for a decrease in maximum amplitude immediately after infusion (HES group, 57.6 ± 6.0 mm vs. 50.9 ± 9.2 mm; HA group, 60.1 ± 7.9 mm vs. 56.6 ± 7.1 mm; p < 0.01), which was restored to preoperative levels 1 h after fluid infusion. Total perioperative fluid balance, blood loss or transfusion, intracranial pressure, and hematological and hemodynamic variables were similar between both groups (p > 0.05). Mortality, length of hospital stay, and clinical complications were similar between both groups. CONCLUSION: These findings suggest that HES and HA might have no significant differences regarding coagulation as assessed by TEG during pediatric intracranial tumor surgery with 20 ml/kg volume pre-loading, which can maintain stable hemodynamics and may represent a new avenue for volume therapy during brain tumor resection in pediatrics. TRIAL REGISTRATION: ChiCTR-IPR- 16009333 , retrospectively registered October 8, 2016.

Potentiation of synaptic transmission in Rat anterior cingulate cortex by chronic itch.

Itch and pain share similar mechanisms. It has been well documented that the anterior cingulate cortex (ACC) is important for pain-related perception. ACC has also been approved to be a potential pruritus-associated brain region. However, the mechanism of sensitization in pruriceptive neurons in the ACC is not clear. In current study, a chronic itch model was established by diphenylcyclopropenone (DCP) application. We found that both the frequency and amplitude of miniature excitatory postsynaptic currents in the ACC were enhanced after the formation of chronic itch. The paired-pulse ratio in ACC neurons recorded from the DCP group were smaller than those recorded in control group at the 50-ms interval. We also observe a significant increase in the AMPA/NMDA ratio in the DCP group. Moreover, an increased inward rectification of AMPARs in ACC pyramidal neurons was observed in the DCP group. Interestingly, the calculated ratio of silent synapses was significantly reduced in the DCP group compared with controls. Taken together, we conclude that a potentiation of synaptic transmission in the ACC can be induced by chronic itch, and unsilencing silent synapses, which probably involved recruitment of AMPARS, contributed to the potentiation of postsynaptic transmission.

Effects of Parecoxib and Fentanyl on nociception-induced cortical activity.

BACKGROUND: Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist) and parecoxib (a selective cyclooxygenase-2 inhibitor) on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals) were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. RESULTS: Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG) desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity), while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. CONCLUSION: Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.