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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 -
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 -
International Journal of Molecular... May 2024Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen...
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture's pain relief and chondroprotective effect in a rat model of collagenase-induced osteoarthritis. Thirty-six adult male Sprague-Dawley rats were divided into three groups: control (saline), positive control (hyaluronic acid), and ex-perimental (peptides). Intra-articular collagenase injections were administered on days 1 and 4 to induce osteoarthritis in the left knees of the rats. Two injections of saline, hyaluronic acid, or the peptides were injected into the same knees of each corresponding group at the beginning of week one and two, respectively. Joint swelling, arthritic pain, and histopathological changes were evaluated. Injection of the peptides significantly reduced arthritic pain compared to the control group, as evidenced by the closer-to-normal weight-bearing and paw withdrawal threshold test results. Histological analyses showed reduced cartilage matrix loss and improved total cartilage degeneration score in the experimental versus the control group. Our findings suggest that intra-articular injection of synthetic deer antler peptides is a promising treatment for osteoarthritis.
Topics: Animals; Injections, Intra-Articular; Antlers; Osteoarthritis, Knee; Male; Deer; Rats; Rats, Sprague-Dawley; Peptides; Disease Models, Animal; Hyaluronic Acid; Cartilage, Articular; Collagenases
PubMed: 38892229
DOI: 10.3390/ijms25116041 -
BMJ Open Jun 2024An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism....
BACKGROUND
An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism. For individuals with cervicogenic headache (CeH), the characteristics of such profiles were never investigated. However, the individual nature of experiencing pain demands profiling within a multidimensional framework including psychosocial lifestyle characteristics. The objective of the current protocol is to assess the pain modulation profile, which includes psychosocial lifestyle characteristics among people with CeH.
METHODS AND ANALYSIS
A protocol is described to map pain modulation profiles in people with CeH. A cross-sectional non-randomised experimental design will be used to assess feasibility of mapping these profiles. The pain modulation profile is composed based on results on the Depression, Anxiety, Stress Scale, Pittsburgh Sleep Quality Index, Headache Impact Test and on responses to temporal summation of pain (pinprick), conditioned pain modulation and widespread hyperalgesia (mechanical pressure pain threshold and cuff algometry). Primary analyses will report results relating to outcomes on feasibility. Secondary analyses will involve an analysis of proportions (%) of the different psychosocial lifestyle profiles and pain profiles.
ETHICS AND DISSEMINATION
Ethical approval was granted by the Ethics Committee Research UZ/KU Leuven (Registration number B3222024001434) on 30 May 2024. Results will be published in peer-reviewed journals, at scientific conferences and, through press releases. Protocol V.3. protocol date: 3 June 2024.
Topics: Humans; Post-Traumatic Headache; Feasibility Studies; Cross-Sectional Studies; Pain Measurement; Adult; Pain Threshold; Male; Female; Life Style
PubMed: 38890144
DOI: 10.1136/bmjopen-2023-074743 -
Journal of Science and Medicine in Sport May 2024Explore if implementing an individualised Sub-Symptom Heart Rate Threshold (SSHeRT) rehabilitation program within 48 hours versus physical rest for 14 days affects...
A controlled early-exercise rehabilitation program commencing within 48 hours of a Sports-Related Concussion improves recovery in UK student-athletes: A prospective cohort study.
OBJECTIVES
Explore if implementing an individualised Sub-Symptom Heart Rate Threshold (SSHeRT) rehabilitation program within 48 hours versus physical rest for 14 days affects recovery following SRC in university-aged student-athletes.
DESIGN
Prospective, observational cohort study.
METHODS
Two UK university-aged student-athlete rugby union cohorts were compared (Physical Rest Group (PRG), n = 140, July 2019-March 2020 and Controlled Early-Exercise Group (CEG), n = 167, July 2021-April 2023). Both groups completed the test battery (Post-Concussion Symptom Scale (PCSS), Immediate Post-Concussion and Cognitive Test (ImPACT), Vestibular-Ocular Motor Screening Tool (VOMS)) during pre-season to provide a baseline and within 48 hours, at 4, 8, 14-days post-SRC and at Return to Play (RTP). The PRG (n = 42) physically rested for 14 days as per the nationwide community guidelines. The CEG (n = 52) followed the SSHeRT rehabilitation program. Individual change to baseline was used in all analyses.
RESULTS
The CEG performed better on ImPACT's verbal memory at 4 (PRG; -5.5 (-10.8-0.0), CEG; 1.0 (-2.0-10.5), p = 0.05) and 14 days (PRG; -2.0 (-10.0-3.0), CEG; 4.0 (-1.0-11.0), p = 0.05) and on the VOMS at 4 (PRG; 3.0 (0.0-12.0), CEG; 0.0 (0.0-5.0), p = 0.03, OR; 2.910) and 14-days post-SRC (PRG; 0.0 (0.0-1.0), CEG; 0.0 (0.0-0.0), OR; 5.914). Near point convergence was better at all time points for the CEG. The CEG was 26.7 % more likely to have RTP within 30 days, and 6.7 and 5.1 times more likely to have resumed non-contact and contact academic activities by 4 days.
CONCLUSIONS
SSHeRT is safe, can be used within 48 hours of a SRC and may hasten university-aged student-athletes recovery following an SRC.
PubMed: 38890020
DOI: 10.1016/j.jsams.2024.05.011 -
Physiological Reports Jun 2024Dynamic resistance exercise may produce reductions in pain locally at the exercising muscle and systemically at non-exercising sites. However, limited research has...
Dynamic resistance exercise may produce reductions in pain locally at the exercising muscle and systemically at non-exercising sites. However, limited research has examined these changes with multiple noxious stimuli. This study examined changes in heat pain threshold (HPT) and pressure pain threshold (PPT) on different musculature after an upper and lower body exercise to compare local and systemic effects. A crossover design with 28 participants (mean age: 21 ± 4 years, 21 female) completed three sessions. Visit one included baseline quantitative sensory testing and 5-repetition maximum (RM) testing for upper (shoulder press) and lower (leg extension) body. In subsequent sessions, participants performed upper or lower body exercises using an estimated 75% 1-RM with pre/post assessment of HPT and PPT at three sites: deltoid, quadriceps, and low back. A significant three-way interaction was observed for HPT (F (1.71, 3.80) = 2.19, p = 0.036, ηp = 0.12) with significant increases in HPT over the quadriceps (p = 0.043) after leg extension and over the deltoid (p = 0.02) after shoulder press. Significant systemic changes were not observed for HPT or PPT. Local but not systemic effects were demonstrated after an acute bout of exercise. Peripheral pain sensitivity may be more responsive to heat stimuli after resistance exercise.
Topics: Humans; Female; Pain Threshold; Male; Resistance Training; Young Adult; Adult; Muscle, Skeletal; Cross-Over Studies; Hot Temperature; Adolescent
PubMed: 38890005
DOI: 10.14814/phy2.16123 -
The role of spinal neurons targeted by corticospinal neurons in central poststroke neuropathic pain.CNS Neuroscience & Therapeutics Jun 2024Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood.
BACKGROUND
Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood.
METHODS
By lesioning the lateral thalamic nuclei, we first established a CPSP model that exhibits mechanical and thermal hypersensitivity. Innocuous mechanical stimuli following the thalamic lesion evoked robust neural activation in somatosensory corticospinal neurons (CSNs), as well as in the deep dorsal horn, where low threshold mechanosensory afferents terminate. In this study, we used viral-based mapping and intersectional functional manipulations to decipher the role of somatosensory CSNs and their spinal targets in the CPSP pathophysiology.
RESULTS
We first mapped the post-synaptic spinal targets of lumbar innervating CSNs using an anterograde trans-synaptic AAV1-based strategy and showed these spinal interneurons were activated by innocuous tactile stimuli post-thalamic lesion. Functionally, tetanus toxin-based chronic inactivation of spinal neurons targeted by CSNs prevented the development of CPSP. Consistently, transient chemogenetic silencing of these neurons alleviated established mechanical pain hypersensitivity and innocuous tactile stimuli evoked aversion linked to the CPSP. In contrast, chemogenetic activation of these neurons was insufficient to induce robust mechanical allodynia typically observed in the CPSP.
CONCLUSION
The CSNs and their spinal targets are required but insufficient for the establishment of CPSP hypersensitivity. Our study provided novel insights into the neural mechanisms underlying CPSP and potential therapeutic interventions to treat refractory central neuropathic pain conditions.
Topics: Animals; Neuralgia; Pyramidal Tracts; Male; Stroke; Neurons; Hyperalgesia; Rats, Sprague-Dawley; Rats; Disease Models, Animal; Spinal Cord
PubMed: 38887838
DOI: 10.1111/cns.14813