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JAMA Psychiatry Feb 2020This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms.
OBJECTIVE
To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores from baseline to 8 weeks.
DESIGN, SETTING, AND PARTICIPANTS
This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only physicians performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist-Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months.
INTERVENTIONS
Paired right-sided SGB or sham procedures at weeks 0 and 2.
MAIN OUTCOMES AND MEASURES
Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori).
RESULTS
Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was -12.6 points (95% CI, -15.5 to -9.7 points) for the group receiving SGB treatments, compared with -6.1 points (95% CI, -9.8 to -2.3 points) for those receiving sham treatment (P = .01).
CONCLUSIONS AND RELEVANCE
In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03077919.
Topics: Anesthetics, Local; Animals; Autonomic Nerve Block; Double-Blind Method; Female; Humans; Injections; Male; Psychiatric Status Rating Scales; Ropivacaine; Stellate Ganglion; Stress Disorders, Post-Traumatic
PubMed: 31693083
DOI: 10.1001/jamapsychiatry.2019.3474 -
Biological Research Jul 2019Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote...
BACKGROUND
Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells.
METHODS
In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine.
RESULTS
Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3.
CONCLUSIONS
Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.
Topics: Anesthetics, Local; Apoptosis; Carcinoma, Hepatocellular; Caspase 3; Cell Line, Tumor; Cell Proliferation; Flow Cytometry; Humans; Liver Neoplasms; Microscopy, Confocal; Microscopy, Fluorescence; Mitochondria; Ropivacaine; Signal Transduction
PubMed: 31300048
DOI: 10.1186/s40659-019-0242-7 -
Anesthesia and Analgesia Aug 2020
Topics: Ropivacaine; Signal Transduction
PubMed: 33031681
DOI: 10.1213/ANE.0000000000004895 -
Gynecologie, Obstetrique, Fertilite &... Jan 2022
Topics: Anesthesia, Obstetrical; Anesthetics, Local; Bupivacaine; Humans; Levobupivacaine; Ropivacaine
PubMed: 34478902
DOI: 10.1016/j.gofs.2021.08.005 -
Anasthesiologie, Intensivmedizin,... Nov 2022Caudal anesthesia is one of the most commonly performed forms of regional anesthesia in childhood, which is relatively easy to learn and very effective. Indications for... (Review)
Review
Caudal anesthesia is one of the most commonly performed forms of regional anesthesia in childhood, which is relatively easy to learn and very effective. Indications for sacral block are all interventions below the costal arch. The puncture can be performed on premature babies and children up to 50 kg body weight. The use of ultrasound increases the success rate and verifies the epidural injection. Bupivacaine and ropivacaine can be combined with adjuvants such as clonidine, morphine or ketamine, which lead to a prolonged effect. In selected patient groups, the operation can also be performed under caudal anesthesia with sedation in order to maintain spontaneous breathing and avoid respiratory complications. This review article gives an overview of caudal anesthesia and offers practical instructions for blocks during general anesthesia and sedation.
Topics: Infant; Child; Humans; Anesthesia, Caudal; Anesthesia, Conduction; Bupivacaine; Ropivacaine; Anesthesia, General
PubMed: 36446359
DOI: 10.1055/a-1467-8624 -
ACS Nano Oct 2023Although surgical resection provides a straightforward and effective treatment for most malignant solid tumors, tumor recurrence and acute postoperative pain continue to...
Although surgical resection provides a straightforward and effective treatment for most malignant solid tumors, tumor recurrence and acute postoperative pain continue to be two big problems associated with this treatment. To resolve these problems, a nanocrystal composite slow-releasing ropivacaine and doxorubicin was fabricated in this study. Briefly, a self-assembling peptide was used to form nanoparticle complexes with the two drugs, based on which homogeneous nanocrystals were obtained by adjusting the pH. In cultured human melanoma cells, the nanocrystals exhibited improved antitumor activity due to a synergistic effect and enhanced cellular uptake of the two drugs. On the other hand, the nanocrystals could slowly release ropivacaine and , generating long-acting analgesia on the rat sciatic nerve block model and incisional pain model. On a nude mouse tumor resection model, the nanocrystals simultaneously suppressed the recurrence of solid tumor and relieved postoperative pain, indicating a potential postoperative treatment for tumor resection patients. This nanocrystal system also suggested a promising and facile strategy for developing multifunctional formulations combining different drugs, which could achieve better therapeutic outcomes in a synergistic and sustained manner.
Topics: Mice; Humans; Rats; Animals; Ropivacaine; Anesthetics, Local; Neoplasm Recurrence, Local; Nerve Block; Pain, Postoperative; Nanoparticles; Doxorubicin
PubMed: 37805931
DOI: 10.1021/acsnano.3c05831 -
Anesthesiology Dec 2023Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury,...
BACKGROUND
Continuous nerve block with ropivacaine is commonly performed after repair surgery for traumatic peripheral nerve injuries. After peripheral nerve injury, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated and contributes to macrophage inflammation. This study investigated whether ropivacaine promotes peripheral nerve regeneration through Nav1.8-mediated macrophage signaling.
METHODS
A sciatic nerve transection-repair (SNT) model was established in adult Sprague-Dawley rats of both sexes. The rats received 0.2% ropivacaine or 10 μM Nav1.8-selective inhibitor A-803467 around the injured site or near the sacrum for 3 days. Nerve regeneration was evaluated using behavioral, electrophysiologic, and morphological examinations. Moreover, myelin debris removal, macrophage phenotype, Nav1.8 expression, and neuropeptide expression were assessed using immunostaining, enzyme-linked immunosorbent assay, and Western blotting.
RESULTS
Compared to the SNT-plus-vehicle group, the sensory, motor, and sensory-motor coordination functions of the two ropivacaine groups were significantly improved. Electrophysiologic (mean ± SD: recovery index of amplitude, vehicle 0.43 ± 0.17 vs. ropivacaine 0.83 ± 0.25, n = 11, P < 0.001) and histological analysis collectively indicated that ropivacaine significantly promoted axonal regrowth (percentage of neurofilament 200 [NF-200]-positive area: vehicle 19.88 ± 2.81 vs. ropivacaine 31.07 ± 2.62, n = 6, P < 0.001). The authors also found that, compared to the SNT-plus-vehicle group, the SNT-plus-ropivacaine group showed faster clearance of myelin debris, accompanied by significantly increased macrophage infiltration and transition from the M1 to M2 phenotype. Moreover, ropivacaine significantly attenuated Nav1.8 upregulation at 9 days after sciatic nerve transection (vehicle 4.12 ± 0.30-fold vs. ropivacaine 2.75 ± 0.36-fold, n = 5, P < 0.001), which coincided with the increased expression of chemokine ligand 2 and substance P. Similar changes were observed when using the selective Nav1.8 channel inhibitor A-803467.
CONCLUSIONS
Continuous nerve block with ropivacaine promotes the structural and functional recovery of injured sciatic nerves, possibly by regulating Nav1.8-mediated macrophage signaling.
Topics: Male; Female; Rats; Animals; Ropivacaine; Rats, Sprague-Dawley; Peripheral Nerve Injuries; Axons; Nerve Regeneration; Sciatic Nerve; Macrophages
PubMed: 37669448
DOI: 10.1097/ALN.0000000000004761 -
Theranostics 2023Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to...
Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8 T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8 T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8 T cells infiltration into tumor and potentiates PTT efficacy. This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.
Topics: Animals; Mice; Phototherapy; Hydrogels; Photothermal Therapy; Ropivacaine; CD8-Positive T-Lymphocytes; Imiquimod; Neoplasms; Indocyanine Green; Analgesics; Pain
PubMed: 37153743
DOI: 10.7150/thno.81325 -
International Journal of Nanomedicine 2022Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for...
INTRODUCTION
Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide.
METHODS
Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect.
RESULTS
Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which could be mineralized to form drug/peptide nanocrystals by adjusting the pH. Under physiological condition, the nanocrystals could release free ropivacaine slowly. As evaluated in rodent models, the anesthetic and analgesic effects of this formulation were significantly extended without causing toxicity.
CONCLUSION
Based on the interaction between ropivacaine and Q11, a controllable biomineralization process could be induced to obtain homogeneous nanocrystals, which could be used as an injectable long-acting analgesic formulation. This crystallization strategy utilizing the peptide-drug interaction also provided a promising pathway to fabricate long-acting formulations for many other small molecular drugs.
Topics: Amides; Analgesia; Anesthetics, Local; Humans; Pain, Postoperative; Peptides; Ropivacaine
PubMed: 35937079
DOI: 10.2147/IJN.S369706 -
Journal of Biochemical and Molecular... Jan 2023Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC)...
Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC) have never been explored. We explored the effects of ropivacaine on the progression of BC in vitro and in vivo. CCK8 assay and EDU staining was conducted to examine cell proliferation. Flow cytometry and transwell assay were performed to evaluate apoptosis and invasion, respectively. Expression of light chain 3 (LC3) was observed through immunofluorescence. Furthermore, the xenograft tumor model of BC was built to detect the effects of ropivacaine in vivo. IHC and TUNEL assay were conducted to detect cell proliferation and apoptosis in vivo. Ropivacaine inhibited the proliferation of T24 and 5639 cells with the 50% inhibitory concentration (IC50) of 20.08 and 31.86 µM, respectively. Ropivacaine suppressed the invasion ability and induces the apoptosis of cells. Besides, ropivacaine triggers obvious autophagy in BC cells. Moreover, ropivacaine blocks the PI3K/AKT signal pathway in BC cells. The impact of ropivacaine on cell viability, motility, and autophagy was reversed by 740 Y-P, the activator of PI3K/AKT signal pathway. The in vivo experiments demonstrated that ropivacaine inhibited the proliferation and mobility of BC. Ropivacaine has anti-carcinoma effects in BC via inactivating PI3K/AKT pathway, providing a new theoretical reference for the use of local anesthetics in the treatment of BC.
Topics: Humans; Proto-Oncogene Proteins c-akt; Ropivacaine; Phosphatidylinositol 3-Kinases; Anesthetics, Local; Cell Line, Tumor; Apoptosis; Urinary Bladder Neoplasms; Autophagy; Cell Proliferation
PubMed: 36193553
DOI: 10.1002/jbt.23233