Project description:BACKGROUND:Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3-0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. METHODS:Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. RESULTS:Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=-0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents ?2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with ?2 mA) among non-diabetic patients (P=0.003). CONCLUSIONS:These findings suggest that stimulation thresholds of 0.3-0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. CLINICAL TRIAL REGISTRATION:NCT01488474.
Project description:Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties. They were made photo-labile by encapsulation of a NIR-triggerable photosensitizer; irradiation at 730 nm led to peroxidation of liposomal lipids, allowing drug release. In vitro, 5.6% of TTX was released upon NIR irradiation, which could be repeated a second time. The formulations were not cytotoxic in cell culture. In vivo, injection of liposomes containing TTX and the photosensitizer caused an initial nerve block lasting 13.5 ± 3.1 h. Additional periods of nerve block could be induced by irradiation at 730 nm. The timing, intensity, and duration of nerve blockade could be controlled by adjusting the timing, irradiance, and duration of irradiation. Tissue reaction to this formulation and the associated irradiation was benign.
Project description:BACKGROUND AND OBJECTIVES:Sciatic nerve block provides analgesia after foot and ankle surgery, but block duration may be insufficient. We hypothesized that perineural dexamethasone and buprenorphine would reduce pain scores at 24 hours. METHODS:Ninety patients received ultrasound-guided sciatic (25 mL 0.25% bupivacaine) and adductor canal (10 mL 0.25% bupivacaine) blockade, with random assignment into 3 groups (30 patients per group): control blocks + intravenous (IV) dexamethasone (4 mg) (control); control blocks + IV buprenorphine (150 ?g) + IV dexamethasone (IV buprenorphine); and nerve blocks containing buprenorphine + dexamethasone (perineural). Patients received mepivacaine neuraxial anesthesia and postoperative oxycodone/acetaminophen, meloxicam, pregabalin, and ondansetron. Patients and assessors were blinded to group assignment. The primary outcome was pain with movement at 24 hours. RESULTS:There was no difference in pain with movement at 24 hours (median score, 0). However, the perineural group had longer block duration versus control (45.6 vs 30.0 hours). Perineural patients had lower scores for "worst pain" versus control (median, 0 vs 2). Both IV buprenorphine and perineural groups were less likely to use opioids on the day after surgery versus control (28.6%, 28.6%, and 60.7%, respectively). Nausea after IV buprenorphine (but not perineural buprenorphine) was severe, frequent, and bothersome. CONCLUSIONS:Pain scores were very low at 24 hours after surgery in the context of multimodal analgesia and were not improved by additives. However, perineural buprenorphine and dexamethasone prolonged block duration, reduced the worst pain experienced, and reduced opioid use. Intravenous buprenorphine caused troubling nausea and vomiting. Future research is needed to confirm and extend these observations.
Project description:BACKGROUND:The number of patients operated on for total knee arthroplasty (TKA) is growing worldwide. Outpatient surgery is defined by a length of stay (LOS) in the hospital of less than 12?h. This can be limited for TKA, with the efficient management of pain and perioperative complications, such as blood loss, affecting a safe hospital discharge. Outpatient TKA with a suitable protocol, including multimodal measures, could improve the success rate of this procedure. Among the main measures, single-shot sciatic nerve block in association with continuous femoral nerve block for pain control needs to be evaluated in outpatient TKA. Furthermore, to promote the safety of the postoperative period and to accelerate rehabilitation, patients who undergo ambulatory TKA could be discharged to a rehabilitation center on the day of surgery to screen adverse events and to optimize the rehabilitation process. This study is designed to assess the benefits of sciatic nerve block in postoperative pain relief for outpatient TKA. METHODS/DESIGN:This randomized prospective controlled study will be conducted in the knee unit of the teaching hospital of the Nice university and will include 40 patients undergoing primary unilateral outpatient TKA, discharged the day of surgery to a private rehabilitation center for enhanced recovery after surgery, after a hospital stay of less than 12?h. Before surgery, all patients will receive a continuous femoral nerve block with 2?mg/ml ropivacaine 20?ml, and then patients will be randomly assigned to receive or not receive a single-shot sciatic nerve block with 2?mg/ml ropivacaine, 20?ml. The primary outcome measure is the success rate of outpatient TKA. This rate is defined by patients discharged from the hospital to a rehabilitation center the day of surgery with no re-hospitalization due to insufficient pain control before the fifth postoperative day. Secondary outcomes include the incidence of major and minor adverse events during the first five postoperative days and measurement of the quality of recovery using the Knee injury and Osteoarthritis Outcome Score and the new International Knee Society scores plus the Quality of Recovery-40 questionnaire. DISCUSSION:The assessment of anesthesia and rehabilitation protocols enabling major orthopedic surgery, such as TKA, is necessary. This randomized controlled study will address the hypothesis that a suitable multimodal protocol including sciatic nerve block could improve pain control and thus improve the success rate of outpatient TKA. TRIAL REGISTRATION:EudraCT, 2016-000226-19. Registered on 15 April 2016.
Project description:Background and objectivesHigh concentrations of local anesthetics may be neurotoxic for diabetic patients. Additive perineural administration of magnesium was reported to decrease the consumption of local anesthetics for nerve block. It was hypothesized that MgSO4 added to dilute ropivacaine was equianalgesic to more concentrated ropivacaine for toe amputations in diabetic patients.MethodsSeventy diabetic patients were allocated into 3 groups: 1) perineural 200 mg MgSO4 added to 0.25% ropivacaine, 2) 0.25% ropivacaine alone, and 3) 0.375% ropivacaine alone. All patients underwent popliteal sciatic nerve block that was guided by ultrasonography using the respective regimens. Time of onset, duration of motor and sensory block were recorded. Spontaneous and evoked pain score, worst pain score, additional analgesic consumption, satisfaction score and initial time of analgesic requirement of each patient were documented up to 48 hours postoperatively.ResultsIn comparison with 0.25% ropivacaine alone, magnesium supplement prolonged the duration of sensory block (p = 0.001), as well as better evoked pain score at 6 hour postoperatively (p = 0.001). In comparison with evoked pain score (1.6/10) in group of 0.375% ropivacaine, magnesium plus 0.25% ropivacaine presented a little higher score (2.5/10) at 6 hour postoperatively (p = 0.001), while lower worst pain score (p = 0.001) and less postoperative total analgesic consumption (p = 0.002).ConclusionsThe regimen of adding 200mg MgSO4 to 0.25% ropivacaine for sciatic nerve block yields equal analgesic effect in comparison with 0.375% ropivacaine. These findings have suggested that supplemental MgSO4 could not improve analgesic quality except reducing the total amount of local anesthetics requirement in diabetic toe amputations with sciatic nerve blocks.
Project description:BackgroundCytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves.MethodsThe sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data.ResultsA total of 46, 52, and 54 upstream cytokines were differentially expressed in the SNs at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRGs at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved.ConclusionsIn summary, these findings provide an overview of the dynamic changes in cytokines in the SNs and DRGs at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.
Project description:Sciatic nerve axon segments from adult mouse were isolated. Following enzymatic digestion, lysate was subjected to incubation with beads conjugated with either clathrin heavy chain antibody or control IgG antibody for clathrin immunoprecipitation. MudPIT analysis was subsequently performed to identify proteins co-precipitating with clathrin.
Project description:Voltage-gated sodium channels (VGSCs) are important for action potentials. There are seven major isoforms of the pore-forming and gate-bearing ?-subunit (Na(V)1) of VGSCs in mammalian neurons, and a given neuron can express more than one isoform. Five of the neuronal isoforms, Na(V)1.1, 1.2, 1.3, 1.6, and 1.7, are exquisitely sensitive to tetrodotoxin (TTX), and a functional differentiation of these presents a serious challenge. Here, we examined a panel of 11 ?-conopeptides for their ability to block rodent Na(V)1.1 through 1.8 expressed in Xenopus oocytes. Although none blocked Na(V)1.8, a TTX-resistant isoform, the resulting "activity matrix" revealed that the panel could readily discriminate between the members of all pair-wise combinations of the tested isoforms. To examine the identities of endogenous VGSCs, a subset of the panel was tested on A- and C-compound action potentials recorded from isolated preparations of rat sciatic nerve. The results show that the major subtypes in the corresponding A- and C-fibers were Na(V)1.6 and 1.7, respectively. Ruled out as major players in both fiber types were Na(V)1.1, 1.2, and 1.3. These results are consistent with immunohistochemical findings of others. To our awareness this is the first report describing a qualitative pharmacological survey of TTX-sensitive Na(V)1 isoforms responsible for propagating action potentials in peripheral nerve. The panel of ?-conopeptides should be useful in identifying the functional contributions of Na(V)1 isoforms in other preparations.
Project description:Sciatic nerve (SN) variaitons can result in interesting clinical presentations. We identified a SN variant that does not fit into preexisting classification schemes. In an adult male cadaver, the SN was found to divide proximally and partly exit through the piriformis muscle. Distal to the piriformis, the two parts of the SN were reunited. Although apparently extremely rare, such a finding should be added to the archives of anatomical variations.
Project description:Lysine acetylation is a reversible Post-translational modification (PTM) involved in a broad array of physiological functions. Recent studies have demonstrated the involvement of protein acetylation in modulating Schwann cells' (SCs) biology and the peripheral nervous system (PNS) regeneration. However, the underlying mechanism is still under investigation. This descriptive study characterized the mouse sciatic nerve (SN) acetylome and explored their cellular distribution. Using a modified workflow for acetylome analysis, we identified 483 acetylated proteins containing 1,442 acetylation modification sites in the SN of adult C57BL/6. Notably, over 70% of identified peptides were acetylated. Bioinformatic analysis suggested that these acetylated proteins are mainly located in the myelin sheath, mitochondrial inner membrane, and actin cytoskeleton, and highlighted the remarkable differences between the mouse SN and brain (PXD027299)acetylome. Further manual annotation indicated that most acetylated proteins were mitochondrial and energy, and cytoskeleton and cell adhesion (> 45%). The acetylate modification of three novel myelin-related proteins were verified, including 2', 3' -cycling-nucleotide 3'-phosphodiesterase (CNP), Neurofilament light polypeptide (NEFL), neurofilament medium/high polypeptide (NFM/H), and periaxin (PRX). Immunofluorescence staining illustrated that, besides the nuclei, the acetylated proteins, including acetylated alpha-tubulin, were mainly co-localized with S100 positive SCs. Together, for the first time, this study provided a comprehensive mouse SN acetylome by using a simple but effective method. Moreover, we demonstrated that the acetylated SN proteins were predominantly located in SCs. These analyses and the method will contribute to understanding and uncovering the roles of protein acetylation in SCs development and PNS regeneration.