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Journal of Anaesthesiology, Clinical... 2024Perioperative lidocaine infusion has many interesting properties such as analgesic effects in the context of enhanced recovery after surgery. However, its use is limited...
BACKGROUND AND AIMS
Perioperative lidocaine infusion has many interesting properties such as analgesic effects in the context of enhanced recovery after surgery. However, its use is limited in liver surgery due to its hepatic metabolism.
MATERIAL AND METHODS
This prospective, monocentric study was conducted from 2020 to 2021. Patients undergoing liver surgery were included. They received a lidocaine infusion protocol until the beginning of hepatic transection (bolus dose of 1.5 mg kg, then a continuous infusion of 2 mg kg h). Plasma concentrations of lidocaine were measured four times during and after lidocaine infusion.
RESULTS
Twenty subjects who underwent liver resection were analyzed. There was 35% of preexisting liver disease before tumor diagnosis, and 75% of liver resection was defined as "major hepatectomy." Plasmatic levels of lidocaine were in the therapeutic range. No blood sample showed a concentration above the toxicity threshold: 1.6 (1.3-2.1) μg ml one hour after the start of infusion, 2.5 (1.7-2.8) μg ml at the end of hepatic transection, 1.7 (1.3-2.0) μg ml one hour after the end of infusion, and 1.2 (0.8-1.4) μg ml at the end of surgery. Comparative analysis between the presence of a preexisting liver disease or not and the association of intraoperative vascular clamping or not did not show significant difference concerning lidocaine blood levels.
CONCLUSION
Perioperative lidocaine infusion seems safe in the field of liver surgery. Nevertheless, additional prospective studies need to assess the clinical usefulness in terms of analgesia and antitumoral effects.
PubMed: 38919445
DOI: 10.4103/joacp.joacp_391_22 -
Journal of Diabetes Research 2024Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level...
Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF-, IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Animals; Male; Middle Aged; Female; Diabetes Mellitus, Experimental; Mice; Aged; Peptide Hormones; Leukocytes, Mononuclear; Pain Threshold; China; Mice, Inbred C57BL
PubMed: 38919263
DOI: 10.1155/2024/4538199 -
Scandinavian Journal of Pain Jan 2024
Topics: Humans; Reproducibility of Results; Exercise; Pain Measurement; Pain Threshold; Male; Female; Adult
PubMed: 38916102
DOI: 10.1515/sjpain-2024-0044 -
Journal of Rehabilitation Medicine Jun 2024To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing.
OBJECTIVE
To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing.
DESIGN
A cross-sectional, descriptive, pilot study conducted during 1 month.
SUBJECTS/PATIENTS
Six patients with previously established post-polio syndrome and related chronic pain.
METHODS
All subjects underwent a neurological examination including neuromuscular function, bedside sensory testing, a thorough pain anamnesis, and pain drawing. Screening for neuropathic pain was done with 2 questionnaires. A comprehensive Quantitative Sensory Testing battery was conducted with z-score transformation of obtained data, enabling comparison with published reference values and the creation of sensory profiles, as well as comparison between the study site (more polio affected extremity) and internal control site (less affected extremity) for each patient.
RESULTS
Derived sensory profiles showed signs of increased prevalence of sensory aberrations compared with reference values, especially Mechanical Pain Thresholds, with significant deviation from reference data in 5 out of 6 patients. No obvious differences in sensory functions were seen between study sites and internal control sites.
CONCLUSION
Post-polio syndrome may be correlated with a mechanical hyperalgesia/allodynia and might be correlated to a somatosensory dysfunction. With lack of evident side-to-side differences, the possibility of a generalized dysfunction in the somatosensory system might be considered.
Topics: Humans; Postpoliomyelitis Syndrome; Pilot Projects; Cross-Sectional Studies; Female; Male; Middle Aged; Aged; Pain Measurement; Pain Threshold; Chronic Pain; Somatosensory Disorders; Adult; Neurologic Examination; Hyperalgesia; Neuralgia
PubMed: 38915293
DOI: 10.2340/jrm.v56.26192 -
Lancet (London, England) Jun 2024Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence,...
Effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention for the prevention of low back pain recurrence in Australia (WalkBack): a randomised controlled trial.
BACKGROUND
Recurrence of low back pain is common and a substantial contributor to the disease and economic burden of low back pain. Exercise is recommended to prevent recurrence, but the effectiveness and cost-effectiveness of an accessible and low-cost intervention, such as walking, is yet to be established. We aimed to investigate the clinical effectiveness and cost-effectiveness of an individualised, progressive walking and education intervention to prevent the recurrence of low back pain.
METHODS
WalkBack was a two-armed, randomised controlled trial, which recruited adults (aged 18 years or older) from across Australia who had recently recovered from an episode of non-specific low back pain that was not attributed to a specific diagnosis, and which lasted for at least 24 h. Participants were randomly assigned to an individualised, progressive walking and education intervention facilitated by six sessions with a physiotherapist across 6 months or to a no treatment control group (1:1). The randomisation schedule comprised randomly permuted blocks of 4, 6, and 8 and was stratified by history of more than two previous episodes of low back pain and referral method. Physiotherapists and participants were not masked to allocation. Participants were followed for a minimum of 12 months and a maximum of 36 months, depending on the date of enrolment. The primary outcome was days to the first recurrence of an activity-limiting episode of low back pain, collected in the intention-to-treat population via monthly self-report. Cost-effectiveness was evaluated from the societal perspective and expressed as incremental cost per quality-adjusted life-year (QALY) gained. The trial was prospectively registered (ACTRN12619001134112).
FINDINGS
Between Sept 23, 2019, and June 10, 2022, 3206 potential participants were screened for eligibility, 2505 (78%) were excluded, and 701 were randomly assigned (351 to the intervention group and 350 to the no treatment control group). Most participants were female (565 [81%] of 701) and the mean age of participants was 54 years (SD 12). The intervention was effective in preventing an episode of activity-limiting low back pain (hazard ratio 0·72 [95% CI 0·60-0·85], p=0·0002). The median days to a recurrence was 208 days (95% CI 149-295) in the intervention group and 112 days (89-140) in the control group. The incremental cost per QALY gained was AU$7802, giving a 94% probability that the intervention was cost-effective at a willingness-to-pay threshold of $28 000. Although the total number of participants experiencing at least one adverse event over 12 months was similar between the intervention and control groups (183 [52%] of 351 and 190 [54%] of 350, respectively, p=0·60), there was a greater number of adverse events related to the lower extremities in the intervention group than in the control group (100 in the intervention group and 54 in the control group).
INTERPRETATION
An individualised, progressive walking and education intervention significantly reduced low back pain recurrence. This accessible, scalable, and safe intervention could affect how low back pain is managed.
FUNDING
National Health and Medical Research Council, Australia.
PubMed: 38908392
DOI: 10.1016/S0140-6736(24)00755-4 -
Scientific Reports Jun 2024Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction....
Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.
Topics: Animals; MicroRNAs; Astrocytes; Mice; Septins; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Male; Neuralgia; Disease Models, Animal
PubMed: 38906977
DOI: 10.1038/s41598-024-65096-z -
Frontiers in Neurology 2024Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with...
BACKGROUND
Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with motor rehabilitative training or delivered before motor training. The necessity of concurrently applying taVNS with motor training for post-stroke motor rehabilitation remains unclear. We aimed to investigate the necessity and advantages of applying the taVNS concurrently with motor training by an electromyography (EMG)-triggered closed-loop system for post-stroke rehabilitation.
METHODS
We propose a double-blinded, randomized clinical trial involving 150 stroke patients assigned to one of three groups: concurrent taVNS, sequential taVNS, or sham control condition. In the concurrent group, taVNS bursts will synchronize with upper extremity motor movements with EMG-triggered closed-loop system during the rehabilitative training, while in the sequential group, a taVNS session will precede the motor rehabilitative training. TaVNS intensity will be set below the pain threshold for both concurrent and sequential conditions and at zero for the control condition. The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Secondary measures include standard upper limb function assessments, as well as EMG and electrocardiogram (ECG) features.
ETHICS AND DISSEMINATION
Ethical approval has been granted by the Medical Ethics Committee, affiliated with Zhujiang Hospital of Southern Medical University for Clinical Studies (2023-QX-012-01). This study has been registered on ClinicalTrials (NCT05943431). Signed informed consent will be obtained from all included participants. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.
DISCUSSION
This study represents a pioneering effort in directly comparing the impact of concurrent taVNS with motor training to that of sequential taVNS with motor training on stroke rehabilitation. Secondly, the incorporation of an EMG-triggered closed-loop taVNS system has enabled the automation and individualization of both taVNS and diverse motor training tasks-a novel approach not explored in previous research. This technological advancement holds promise for delivering more precise and tailored training interventions for stroke patients. However, it is essential to acknowledge a limitation of this study, as it does not delve into examining the neural mechanisms underlying taVNS in the context of post-stroke rehabilitation.
PubMed: 38903173
DOI: 10.3389/fneur.2024.1379451 -
BioRxiv : the Preprint Server For... Jun 2024G protein-coupled receptors (GPCRs) are efficient Guanine nucleotide exchange factors (GEFs) and exchange GDP to GTP on the Gα subunit of G protein heterotrimers in...
G protein-coupled receptors (GPCRs) are efficient Guanine nucleotide exchange factors (GEFs) and exchange GDP to GTP on the Gα subunit of G protein heterotrimers in response to various extracellular stimuli, including neurotransmitters and light. GPCRs primarily broadcast signals through activated G proteins, GαGTP, and free Gβγ, and are major disease drivers. Evidence shows that the ambient low threshold signaling required for cells is likely supplemented by signaling regulators such as non-GPCR GEFs and Guanine nucleotide Dissociation Inhibitors (GDIs). Activators of G protein Signaling 3 (AGS3) are recognized as a GDI involved in multiple health and disease-related processes. Nevertheless, understanding of AGS3 is limited, and no significant information is available on its structure-function relationship or signaling regulation in living cells. Here, we employed structure-guided engineering of a novel optogenetic GDI, based on the AGS3's G protein regulatory (GPR) motif, to understand its GDI activity and induce standalone Gβγ signaling in living cells on optical command. Our results demonstrate that plasma membrane recruitment of OptoGDI efficiently releases Gβγ, and its subcellular targeting generated localized PIP3 and triggered macrophage migration. Therefore, we propose OptoGDI as a powerful tool for optically dissecting GDI-mediated signaling pathways and triggering GPCR-independent Gβγ signaling in cells and .
PubMed: 38895415
DOI: 10.1101/2024.06.04.597473 -
Journal of Clinical Medicine May 2024: The investigation of C-fiber-evoked ultralow-level responses (ULEPs) at somatic sites is difficult in clinical practice but may be useful in patients with small fiber...
: The investigation of C-fiber-evoked ultralow-level responses (ULEPs) at somatic sites is difficult in clinical practice but may be useful in patients with small fiber neuropathy. Aim: The aim of the study was to investigate changes in LEPs and ULEPs in patients with fibromyalgia affected or not by abnormal intraepidermal innervation. : We recorded LEPs and ULEPs of the hand, thigh and foot in 13 FM patients with a normal skin biopsy (NFM), 13 patients with a reduced intraepidermal nerve fiber density (IENFD) (AFM) and 13 age-matched controls. We used a YAP laser, changing the energy and spot size at the pain threshold for LEPs and at the heat threshold for ULEPs. : ULEPs occurred at a small number of sites in both the NFM and AFM groups compared to control subjects. The absence of ULEPs during foot stimulation was characteristic of AFM patients. The amplitude of LEPs and ULEPs was reduced in patients with AFM at the three stimulation sites, and a slight reduction was also observed in the NFM group. : The present preliminary results confirmed the reliability of LEPs in detecting small fiber impairments. The complete absence of ULEPs in the upper and lower limbs, including the distal areas, could confirm the results of LEPs in patients with small fiber impairments. Further prospective studies in larger case series could confirm the present findings on the sensitivity of LEP amplitude and ULEP imaging in detecting small fiber impairments and the development of IENFD in FM patients.
PubMed: 38892789
DOI: 10.3390/jcm13113078 -
Journal of Clinical Medicine May 2024: The aim of this meta-analysis was to determine the effects of respiratory muscle training (RMT) on functional ability, pain-related outcomes, and respiratory function... (Review)
Review
Effects of Respiratory Muscle Training on Functional Ability, Pain-Related Outcomes, and Respiratory Function in Individuals with Low Back Pain: Systematic Review and Meta-Analysis.
: The aim of this meta-analysis was to determine the effects of respiratory muscle training (RMT) on functional ability, pain-related outcomes, and respiratory function in individuals with sub-acute and chronic low back pain (LBP). : The study selection was as follows: (participants) adult individuals with >4 weeks of LBP; (intervention) RMT; (comparison) any comparison RMT (inspiratory or expiratory or mixed) versus control; (outcomes) postural control, lumbar disability, pain-related outcomes, pain-related fear-avoidance beliefs, respiratory muscle function, and pulmonary function; and (study design) randomized controlled trials. : 11 studies were included in the meta-analysis showing that RMT produces a statistically significant increase in postural control (mean difference (MD) = 21.71 [12.22; 31.21]; decrease in lumbar disability (standardized mean difference (SMD) = 0.55 [0.001; 1.09]); decrease in lumbar pain intensity (SMD = 0.77 [0.15; 1.38]; increase in expiratory muscle strength (MD = 8.05 [5.34; 10.76]); and increase in forced vital capacity (FVC) (MD = 0.30 [0.03; 0.58]) compared with a control group. However, RMT does not produce an increase in inspiratory muscle strength (MD = 18.36 [-1.61; 38.34]) and in forced expiratory volume at the first second (FEV1) (MD = 0.36 [-0.02; 0.75]; and in the FEV1/FVC ratio (MD = 1.55 [-5.87; 8.96]) compared with the control group. : RMT could improve expiratory muscle strength and FVC, with a moderate quality of evidence, whereas a low quality of evidence suggests that RMT could improve postural control, lumbar disability, and pain intensity in individuals with sub-acute and chronic LBP. However, more studies of high methodological quality are needed to strengthen the results of this meta-analysis.
PubMed: 38892764
DOI: 10.3390/jcm13113053