Effects of Distinct Force Magnitude of Spinal Manipulative Therapy on Blood Biomarkers of Inflammation: A Proof of Principle Study in Healthy Young Adults.

OBJECTIVES: The purpose of this preliminary study was to determine the influence of thoracic spinal manipulation therapy (SMT) of different force magnitudes on blood biomarkers of inflammation in healthy adults. METHODS: Nineteen healthy young adults (10 female, age: 25.6 ± 1.2 years) were randomized into the following 3 groups: (1) control (preload only), (2) single thoracic SMT with a total peak force of 400N, and (3) single thoracic SMT with a total peak force of 800N. SMT was performed by an experienced chiropractor, and a force-plate embedded treatment table (Force Sensing Table Technology) was used to determine the SMT force magnitudes applied. Blood samples were collected at pre intervention (baseline), immediately post intervention, and 20 minutes post intervention. A laboratory panel of 14 different inflammatory biomarkers (pro, anti, dual role, chemokine, and growth factor) was assessed by multiplex array. Change scores from baseline of each biomarker was used for statistical analysis. Two-way repeated-measures analysis of variance was used to investigate the interaction and main effects of intervention and time on cytokines, followed by Tukey's multiple comparison test (P ≤ .05). RESULTS: A between-group (800N vs 400N) difference was observed on interferon-gamma, interleukin (IL)-5, and IL-6, while a within-group difference (800N: immediately vs 20 minutes post-intervention) was observed on IL-6 only. CONCLUSION: In this study, we measured short-term changes in plasma cytokines in healthy young adults and found that select plasma pro-inflammatory and dual-role cytokines were elevated by higher compared to lower SMT force. Our findings aid to advance our understanding of the potential relationship between SMT force magnitude and blood cytokines and provide a healthy baseline group with which to compare similar studies in clinical populations in the future.

Exploring the effect of capsaicin-induced central sensitization on the upper limb nociceptive withdrawal reflex threshold.

The nociceptive withdrawal reflex (NWR) threshold is commonly employed in the lower limb to assess clinical and experimentally induced pain. However, no studies to date have investigated changes in spinal nociception in the upper limb, via the NWR threshold, following experimentally induced central sensitization (CS). We tested the hypothesis that experimentally induced CS of the C5-C6 spinal segment significantly reduces NWR thresholds in muscles of the upper limb. Upper limb NWR thresholds from 20 young, healthy adults were assessed by applying noxious electrical stimuli to the right index finger and recording muscle activity from the biceps brachii (BI), triceps brachii (TRI), flexor carpi ulnaris (WF), and extensor carpi radialis longus (WE) muscles via surface electromyography. Topical cream (either 0.075% capsaicin, or control) was applied to the C5-C6 dermatome of the lateral forearm (50 cm2). NWR thresholds were compared at baseline, and four 10-min intervals after topical application. WF muscle NWR thresholds were significantly reduced in the capsaicin session compared to control, while TRI muscle NWR thresholds were significantly reduced 40 min after capsaicin application only (p < 0.05). There were no significant differences for BI or WE muscle NWR thresholds. We observed poor to moderate test-retest reliability for all upper limb NWR thresholds, a key contributor to the selective reduction in NWR thresholds among muscles. Accordingly, while our findings demonstrate some comparability to previously reported lower limb NWR studies, we concurrently report limitations of the upper limb NWR technique. Further exploration of optimal parameters for upper limb NWR acquisition is needed.

Re-Examining Myofascial Pain Syndrome: Toward Biomarker Development and Mechanism-Based Diagnostic Criteria.

PURPOSE OF REVIEW: We discuss the need for a mechanism-based diagnostic framework with a focus on the development of objective measures (e.g., biomarkers) that can potentially be added to the diagnostic criteria of the syndrome. Potential biomarkers are discussed in relation to current knowledge on the pathophysiology of myofascial pain syndrome (MPS), including alterations in redox status, inflammation, and the myofascial trigger point (MTrP) biochemical milieu, as well as imaging and neurophysiological outcomes. Finally, we discuss the long-term goal of conducting a Delphi survey, to assess the influence of putative MPS biomarkers on clinician opinion, in order to ultimately develop new criteria for the diagnosis of MPS. RECENT FINDINGS: Myofascial pain syndrome (MPS) is a prevalent healthcare condition associated with muscle weakness, impaired mood, and reduced quality of life. MPS is characterized by the presence of myofascial trigger points (MTrPs): stiff and discrete nodules located within taut bands of skeletal muscle that are painful upon palpation. However, physical examination of MTrPs often yields inconsistent results, and there is no gold standard by which to diagnose MPS. The current MPS diagnostic paradigm has an inherent subjectivity and the absence of correlation with the underlying pathophysiology. Recent advancements in ultrasound imaging, systemic biomarkers, MTrP-specific biomarkers, and the assessment of dysfunction in the somatosensorial system may all contribute to improved diagnostic effectiveness of MPS.

Prolonged exercise training improves the acute type II muscle fibre satellite cell response in healthy older men.

KEY POINTS: Skeletal muscle stem cells, termed satellite cells, play a crucial role in repair and remodelling of muscle in response to exercise An age-related decline in satellite cell number and/or function has been hypothesized to be a key factor in the development of sarcopenia and/or the blunted muscle fibre adaptive response to prolonged exercise training in older persons We report that performing prolonged exercise training improves the acute type II muscle fibre satellite cell response following a single bout of resistance exercise in older men. The observed improvement in muscle satellite function is associated with an increase in muscle fibre capillarization following exercise training suggesting a possible functional link between capillarization and satellite cell function. ABSTRACT: Age-related type II muscle fibre atrophy is accompanied by a fibre type-specific decline in satellite cell number and function. Exercise training restores satellite cell quantity in older adults; however, whether it can restore the impaired satellite cell response to exercise in older adults remains unknown. Therefore we assessed the acute satellite cell response to a single exercise session before and after prolonged exercise training in older men. Fourteen older men (74 ± 8 years) participated in a 12-week exercise training programme (resistance exercise performed twice per week, high intensity interval training once per week). Before and after training, percutaneous biopsies from the vastus lateralis muscle were taken prior to and following 24 and 48 h of post-exercise recovery. Muscle fibre characteristics were evaluated by immunohistochemistry and mRNA expression by RT-PCR. Whereas no changes were observed in type II muscle fibres, type I muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise before the exercise training programme (P < 0.01). Following the exercise training programme, both type I and type II muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise (P < 0.05). The greater acute increase in type II muscle fibre satellite cell content at 24 h post-exercise recovery after training was correlated with an increase in type II muscle fibre capillarization (r = 0.671, P = 0.012). We show that the acute muscle satellite cell response following exercise can be improved by prolonged exercise training in older men.

Ingestion of a Multi-Ingredient Supplement Does Not Alter Exercise-Induced Satellite Cell Responses in Older Men.

Background: Nutritional supplementation can have beneficial effects on body composition, strength, and function in older adults. However, whether the response of satellite cells can be altered by nutritional supplementation in older adults remains unknown. Objective: We assessed whether a multi-ingredient protein-based supplement taken over a prolonged period of time could alter the muscle satellite cell response after exercise in older men. Methods: Twenty-seven older men [mean ± SD age: 73 ± 1 y; mean ± SD body mass index (kg/m2): 28 ± 1] participated in a randomized double-blind experiment. Participants were randomly divided into an experimental (EXP) group (n = 13) who consumed a multi-ingredient protein-based supplement [30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg Ca, and 1500 mg n-3 (ω-3) polyunsaturated fatty acids] 2 times/d for 7 wk or a control (CON; 22 g maltodextrin) group (n = 14). After 7 wk of supplementation, all participants performed a single resistance exercise session, and muscle biopsy samples were taken from the vastus lateralis before and 24 and 48 h after exercise. Immunohistochemistry was used to assess the change in type I and II muscle fiber satellite cell content and activation status of the cells. In addition, mRNA expression of the myogenic regulatory factors was determined by using reverse transcriptase-polymerase chain reaction. Results: In response to the single bout of exercise, type I muscle fiber satellite cell content was significantly increased at 24 h (0.132 ± 0.015 and 0.131 ± 0.011 satellite cells/fiber in CON and EXP groups, respectively) and 48 h (0.126 ± 0.010 and 0.120 ± 0.012 satellite cells/fiber in CON and EXP groups, respectively) compared with pre-exercise (0.092 ± 0.007 and 0.118 ± 0.017 satellite cells/fiber in CON and EXP groups, respectively) muscle biopsy samples (P < 0.01), with no difference between the 2 groups. In both groups, we observed no significant changes in type II muscle fiber satellite cell content after exercise. Conclusion: Ingesting a multi-ingredient protein-based supplement for 7 wk did not alter the type I or II muscle fiber satellite cell response during postexercise recovery in older men. This trial was registered at www.clinicaltrials.gov as NCT02281331.

The Relationship between Rate of Algometer Application and Pain Pressure Threshold in the Assessment of Myofascial Trigger Point Sensitivity.

BACKGROUND: Pressure algometry is a commonly employed technique in the assessment of both regional and widespread musculoskeletal pain. Despite its acceptance amongst clinicians and scientists, the relationship between rate of pressure application (RoA) and pain pressure threshold (PPT) remains poorly understood. We set out to test the hypothesis that a strong, positive, linear relationship exists between the RoA and the PPT within the infraspinatus of young healthy subjects. METHODS: Thirty-three participants were randomly recruited from the local university community. PPT measures were recorded from a clinically identified myofascial trigger point within the right infraspinatus muscle during pressure algometry. A total of 2 PPT measures were recorded using each of 3 different RoAs, including low (15 N/s), medium (35 N/s), and high (55 N/s). Three baseline trials were also conducted at 30 N/s. The Pearson's correlation coefficient between RoA and PPT was calculated for each subject and averaged across participants. RESULTS: The mean(SD) correlation between subjects was 0.77 (0.19), and the mean (SD) slope of the linear regression was 0.13 (0.09). CONCLUSION: Our results demonstrate that there is a strong, linear relationship between the RoA and PPT when using the pressure algometry technique. The low slope between RoA and PPT suggests clinicians can rely on PPT assessments despite small RoA fluctuations. Future research should explore this relationship further in a clinical population and in other muscles affected by chronic myofascial pain. Advancing cost-effective, reliable, and clinically feasible tools such as algometry is important to enhancing the diagnosis and management of chronic myofascial pain.

Dynamic DTI (dDTI) shows differing temporal activation patterns in post-exercise skeletal muscles.

OBJECT: To assess post-exercise recovery of human calf muscles using dynamic diffusion tensor imaging (dDTI). MATERIALS AND METHODS: DTI data (6 directions, b = 0 and 400 s/mm2) were acquired every 35 s from seven healthy men using a 3T MRI, prior to (4 volumes) and immediately following exercise (13 volumes, ~7.5 min). Exercise consisted of 5-min in-bore repetitive dorsiflexion-eversion foot motion with 0.78 kg resistance. Diffusion tensors calculated at each time point produced maps of mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and signal at b = 0 s/mm2 (S0). Region-of-interest (ROI) analysis was performed on five calf muscles: tibialis anterior (ATIB), extensor digitorum longus (EDL) peroneus longus (PER), soleus (SOL), and lateral gastrocnemius (LG). RESULTS: Active muscles (ATIB, EDL, PER) showed significantly elevated initial MD post-exercise, while predicted inactive muscles (SOL, LG) did not (p < 0.0001). The EDL showed a greater initial increase in MD (1.90 × 10-4mm2/s) than ATIB (1.03 × 10-4mm2/s) or PER (8.79 × 10-5 mm2/s) (p = 7.40 × 10-4), and remained significantly elevated across more time points than ATIB or PER. Significant increases were observed in post-exercise EDL S0 relative to other muscles across the majority of time points (p < 0.01 to p < 0.001). CONCLUSIONS: dDTI can be used to differentiate exercise-induced changes between muscles. These differences are suggested to be related to differences in fiber composition.

Safe MRI-Compatible electrical muscle stimulation (EMS) system.

PURPOSE: To develop an inexpensive magnetic resonance imaging (MRI)-compatible electrical muscle stimulation (EMS) unit and test it for safety and efficacy. MATERIALS AND METHODS: A simple MRI-compatible EMS device was developed using radiofrequency (RF) translucent electrodes at 3T. RF heating concerns were assessed using optical temperature measurements at electrode sites, during scanning of a phantom. EMS efficacy and consistency was investigated through in vivo (n = 5) measures of 31 P-MRS phosphocreatine (PCr) reduction, and altered blood oxygen level-dependent (BOLD) signal and the results were compared to effects from equivalent voluntary effort on the same subjects. RESULTS: The presence of an EMS pulse did not interfere with the T2 * signal in a phantom. However, signal-to-noise ratio (SNR) was reduced by 70% at electrode sites, but only by 10% 4 cm distally. Under RF intense conditions, the temperature at the electrode site increased by only 4.7°C over a 16-minute time span. In vivo muscle stimulation resulted in 13.5 ± 1.8% reduction in PCr, which was not significantly (P < 0.195) different from voluntary contraction. Reproducible muscle BOLD signal changes following EMS were noted, with a maximal increase of 10.0 ± 2.6% seen in the central soleus. For soleus and gastrocnemius compartments, EMS produced significantly higher BOLD signal change compared to voluntary contraction (P < 0.05). CONCLUSION: A safe and inexpensive MRI-compatible EMS unit can be easily built for evaluating muscle function and metabolism within a 3T MRI scanner. Clinical applications might include evaluating skeletal muscle function in patients with limited or absent voluntary skeletal motor function or inadequate exercise capacity. J. Magn. Reson. Imaging 2016;44:1530-1538.

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the "post-inflammatory brain syndrome" PIBS.

Post-concussion syndrome is an aggregate of symptoms that commonly present together after head injury. These symptoms, depending on definition, include headaches, dizziness, neuropsychiatric symptoms, and cognitive impairment. However, these symptoms are common, occurring frequently in non-head injured controls, leading some to question the existence of post-concussion syndrome as a unique syndrome. Therefore, some have attempted to explain post-concussion symptoms as post-traumatic stress disorder, as they share many similar symptoms and post-traumatic stress disorder does not require head injury. This explanation falls short as patients with post-concussion syndrome do not necessarily experience many key symptoms of post-traumatic stress disorder. Therefore, other explanations must be sought to explain the prevalence of post-concussion like symptoms in non-head injury patients. Many of the situations in which post-concussion syndrome like symptoms may be experienced such as infection and post-surgery are associated with systemic inflammatory responses, and even neuroinflammation. Post-concussion syndrome itself has a significant neuroinflammatory component. In this review we examine the evidence of neuroinflammation in post-concussion syndrome and the potential role systemic inflammation plays in post-concussion syndrome like symptoms. We conclude that given the overlap between these conditions and the role of inflammation in their etiologies, a new term, post-inflammatory brain syndromes (PIBS), is necessary to describe the common outcomes of many different inflammatory insults. The concept of post-concussion syndrome is in its evolution therefore, the new term post-inflammatory brain syndromes provides a better understanding of etiology of its wide-array of symptoms and the wide array of conditions they can be seen in.

Diffusion tensor imaging of the normal foot at 3 T.

OBJECTIVE: The objective of this study was to establish normative diffusion tensor imaging (DTI) eigenvalues (λ1,λ2,λ3), apparent diffusion coefficient, and fractional anisotropy in asymptomatic foot muscles. METHODS: Ten healthy adults (mean [SD], 25.9 [4.3] years) were examined using a 3-T magnetic resonance imaging scanner. Diffusion tensor imaging indices were evaluated in 5 muscles in the foot: quadratus plantae, abductor hallucis, flexor hallucis brevis, flexor digitorum brevis, and abductor digiti minimi. Signal-to-noise ratio was also measured for each muscle. RESULTS: In the various foot muscles, λ1 ranged from 1.88 × 10 to 2.14 × 10 mm/s, λ2 ranged from 1.39 × 10 to 1.48 × 10 mm/s, and λ3 ranged from 0.91 × 10 to 1.27 × 10 mm/s; apparent diffusion coefficient ranged from 1.48 × 10 to 1.55 × 10 mm/s; and fractional anisotropy ranged from 0.21 to 0.40. Statistical differences were seen in some eigenvalues between muscle pairs. Mean signal-to-noise ranged from 47.5 to 69.1 in the various muscles examined. CONCLUSIONS: Assessment of anisotropy of water diffusion in foot muscles was feasible using DTI. The measured DTI metrics in the foot were similar to those in calf and thigh skeletal muscles.

Denoising of the gradient artifact present in simultaneous studies of muscle blood oxygen level dependent (BOLD) signal and electromyography (EMG).

The MR-induced gradient artifact affects EMG recordings during simultaneous muscle BOLD/EMG acquisitions. However, no dedicated hardware can remove the gradient artifact easily, and alternative methods are expensive and time-consuming. This study aimed to develop three denoising methods requiring different processing levels and MR-compatible hardware. At two time points, surface EMG was recorded from the lower leg of 6 participants (50:50 sex ratio, age = 26.24.6 yrs., height = 173.59.2 cm, weight = 71.511.4 kg) using a plantar flexion-based block design consisting of 30s of rest followed by 30s of flexion for 5 min, under three conditions: inside the MRI bore, with and without a BOLD sequence (3 T, BOLD sequence, GRE EPI, 10 slices, 64×64 matrix, 2 mm thickness, and TE/TR/flip = 35/3000 ms/70), and outside the MRI environment. Simultaneous BOLD/EMG recordings were denoised using average artifact subtraction with three methods of artifact template creation, each having varying timing and hardware requirements. Method M1 builds the artifact template by recording the scanner triggers coming from the MRI; M2 creates the artifact template with a constant artifact period computed as TR/[number of slices]; M3 estimates the artifact template by looking at the periodicity of the gradient artifact located in the EMG recordings. Following postprocessing, SNR analysis was performed, comparing rest-to-flexion periods, to assess the efficacy of denoising methods and to compare differences between conditions. Linear mixed-effects models showed no significant differences in the mean SNR between denoising methods (p = 0.656). Furthermore, EMG SNR measurements were significantly affected by the magnetic environment (p < 0.05) but not by muscle fatigue over time (p = 0.975). EMG recordings contaminated with gradient artifacts during simultaneous BOLD/EMG can be efficiently denoised using all proposed methods, with two methods requiring no extra hardware. With minimal post-processing, EMG can easily be performed during muscle BOLD MRI studies.

Targeting skeletal muscle health with exercise in people with type 1 diabetes: A protocol for HOMET1D, a prospective observational trial with matched controls.

INTRODUCTION: Individuals with type 1 diabetes (T1D) experience a complex set of alterations to skeletal muscle metabolic, neuromuscular, and vascular health; collectively referred to as diabetic myopathy. While the full scope of diabetic myopathy is still being elucidated, evidence suggests that even when individuals with T1D are physically active, indices of myopathy still exist. As such, there is a question if adherence to current physical activity guidelines elicits improvements in skeletal muscle health indices similarly between individuals with and without T1D. The objectives of this trial are to: 1) compare baseline differences in skeletal muscle health between adults with and without T1D, 2) examine the association between participation in a home-based exercise program, detraining, and retraining, with changes in skeletal muscle health, and 3) examine the roles of age and sex on these associations. METHODS AND ANALYSIS: This will be a prospective interventional trial. Younger (18-30 years) and older (45-65 years) males and females with T1D and matched individuals without T1D will engage in a four-phase, 18-week study sequentially consisting of a one-week lead-in period, 12-week exercise training program, one-week detraining period, and four-week retraining period. The exercise program will consist of aerobic and resistance exercise based on current guidelines set by Diabetes Canada. Metabolic, neuromuscular, and vascular outcome measures will be assessed four times: at baseline, post-exercise program, post-detraining, and post-retraining. Differences in baseline metrics between those with and without T1D will be examined with independent sample t-tests, and with two-way analyses of variance for age- and sex-stratified analyses. Changes across the duration of the study will be examined using mixed-model analyses. DISSEMINATION: Findings from this research will be shared locally and internationally with research participants, clinicians, diabetes educators, and patient advocacy organizations via in-person presentations, social media, and scientific fora. TRIAL REGISTRATION NUMBER: NCT05740514.

Quantitative DTI assessment in human lumbar stabilization muscles at 3 T.

OBJECTIVES: To characterize diffusion tensor imaging (DTI) tensor eigenvalues (λ1, λ2, λ3), fractional anisotropy, mean diffusivity, and radial diffusivity in healthy lumbar musculature. METHODS: Seventeen healthy subjects (10 men, 7 women; mean age, 28 ± 7 years) were scanned using a 3.0-T magnetic resonance imaging. Axial DTI was performed using 15 diffusion directions (b = 400 mm/s) at the L4 level. Oswestry Low Back Pain and Godin Physical Activity questionnaires were administered to rule out underlying lower back problems. RESULTS: Skeletal muscle DTI metrics were similar to those previously published. All measurements showed low coefficients of variation, except for quadratus lumborum. Laterality was not significant. Significant sex differences were observed in the quadratus lumborum (P < 0.05). Significant correlations were found between subjects' weight and body mass index with fractional anisotropy and λ1 of the multifidus muscles. CONCLUSIONS: The DTI metrics in paraspinal muscles can be reliably measured and are influenced by body mass index and weight but not by age or physical activity.

Myofascial Pain as an Unseen Comorbidity in Osteoarthritis: A Scoping Review.

OBJECTIVE: This review aimed to identify, summarize, and appraise the evidence supporting the coexistence of myofascial pain (MPS) and trigger points (MTrP) in osteoarthritis (OA), and the effectiveness of MTrPs treatments in OA-related pain and physical function outcomes. METHODS: Three databases were searched from inception to June 2022. We included observational and experimental studies to fulfill our 2 study aims. Two independent reviewers conducted 2-phase screening procedures and risk of bias using checklist tools for cross-sectional, quasi-experimental, and randomized control trials. Patient characteristics, findings of active and latent MTrPs in relevant muscles, treatments, and pain and physical function outcomes were extracted from low-risk bias studies. RESULTS: The literature search yielded 2898 articles, of which 6 observational and 7 experimental studies had a low bias risk and the data extracted. Active MTrPs in knee OA patients was more evident in the quadriceps and hamstring muscles than in healthy individuals. Dry needling on active MTrPs improved pain and physical function in the short term compared with sham treatment in hip OA patients. In knee OA, dry needling on latent or active MTrPs improved pain and functional outcomes compared with sham needling but did not result in better pain and physical outcomes when combined with a physical exercise program. DISCUSSION: The presence of active versus latent MTrPs seems to be a more sensitive discriminating feature of OA given that latent is often present in OA and healthy individuals. Dry needling on active MTrPs improved pain and physical function in the short term compared with sham treatment in hip OA patients. However, the small sample size and the few number of studies limit any firm recommendation on the treatment. REGISTRY: The study protocol was prospectively registered in Open Science Framework (https://doi.org/10.17605/OSF.IO/8DVU3).

A non-invasive 13CO2 breath test detects differences in anabolic sensitivity with feeding and heavy resistance exercise in healthy young males: a randomized control trial.

There are limited tools to measure anabolic sensitivity non-invasively in response to acute physiological stimuli, which represents a challenge for research in free-living settings and vulnerable populations. We tested the ability of a stable isotope breath test to detect changes in leucine oxidation (OX) and leucine retention (intake-OX) across a range of anabolic sensitivities. Healthy males ingested a beverage containing 0.25 g·kg-1 protein and 0.75 g·kg-1 carbohydrate with the leucine content enriched to 5% with l-[1-13C]leucine at rest (FED) or after a bout of resistance exercise (EXFED), with a parallel group consuming only the tracer (FAST). Concurrent primed-constant infusions of l-[5,5,5-2H3]leucine revealed high peripheral bioavailability for FED (∼81%), EXFED (∼80%), and FAST (∼117%). After beverage ingestion, whole-body protein synthesis was greater in FED and EXFED than FAST. OX was greater in FED and EXFED than FAST, with OX lower in EXFED than FED. Leucine retention demonstrated expected physiological differences in anabolic sensitivity (EXFED > FED > FAST). We demonstrated that a non-invasive breath test based on an amino acid (leucine) that is preferentially metabolized in peripheral (muscle) tissues can detect differences in anabolic sensitivity. Future studies could examine this test within a variety of populations experiencing muscle growth or atrophy. This study was registered as a Clinical Trial at ClinicalTrials.gov (no. NCT04887727). Novelty: An oral l-[1-13C]leucine breath test can detect greater anabolic sensitivity after feeding and resistance exercise. This tool may be applied in growing (e.g., children) or wasting (e.g., aging) populations where invasive procedures are not possible.

The nociceptive flexion reflex: a scoping review and proposed standardized methodology for acquisition in those affected by chronic pain.

The nociceptive flexion reflex (NFR) is used in neurophysiological research as an objective measure of nociception. NFR thresholds are reduced in numerous chronic pain pathologies, which are indicative of common central hyperexcitability within conditions. However, variation exists in both the NFR assessment and determinants of NFR threshold among research groups. Our purpose was to provide a review of the recent literature to (a) confirm the NFR threshold's efficacy in identifying those with chronic pain compared to controls and (b) provide a narrative synthesis on the current methodology used to assess the NFR in clinical populations. We conducted a review of multiple databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and Cochrane Library), including articles that reported controlled clinical studies of humans, in English, comparing NFR thresholds within chronic pain conditions to matched control subjects, published since the last NFR review in 2010. Our search resulted in nine studies included in our narrative synthesis and eight studies included in a meta-analysis. There was a significant pooled standardized mean difference in NFR threshold between chronic pain conditions and controls (-0.94, 95% confidence interval (CI) -1.33 to -0.55, p < 0.0001), with substantial heterogeneity of pooled estimates (I 2 = 87%, τ 2 = 0.41, Q = 76.13, the degrees of freedom (df) = 11, p < 0.0001). Significant variations in participant positioning, stimulation parameters and determinants of the NFR threshold were evident among included studies. We provided a narrative synthesis on the methodologies of included studies, as a recommendation for future studies in the assessment of the NFR in chronic pain.

Brain-derived neurotrophic factor is associated with human muscle satellite cell differentiation in response to muscle-damaging exercise.

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophin brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (age, 21 ± 0.5 years) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (Pre), and at 6 h, 24 h, 72 h, and 96 h postexercise. BDNF was not detected in any quiescent (Pax7+/MyoD-) SCs across the time-course. BDNF colocalized to 39% ± 5% of proliferating (Pax7+/MyoD+) cells at Pre, which increased to 84% ± 3% by 96 h (P < 0.05). BDNF was only detected in 13% ± 5% of differentiating (Pax7-/MyoD+) cells at Pre, which increased to 67% ± 4% by 96 h (P < 0.05). The number of myogenin+ cells increased 95% from Pre (1.6 ± 0.2 cells/100 myofibres (MF)) at 24 h (3.1 ± 0.3 cells/100 MF) and remained elevated until 96 h (cells/100 MF), P < 0.05. The proportion of BDNF+/myogenin+ cells was 26% ± 0.3% at Pre, peaking at 24 h (49% ± 3%, P < 0.05) and remained elevated at 96 h (P < 0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and early differentiation. Novelty BDNF is associated with SC response to muscle injury. BDNF was not detected in nonactivated (quiescent) SCs. BDNF is associated with late proliferation and early differentiation of SCs in vivo in humans.

Leucine-enriched amino acids maintain peripheral mTOR-Rheb localization independent of myofibrillar protein synthesis and mTORC1 signaling postexercise.

Postexercise protein ingestion can elevate rates of myofibrillar protein synthesis (MyoPS), mTORC1 activity, and mTOR translocation/protein-protein interactions. However, it is unclear if leucine-enriched essential amino acids (LEAA) can similarly facilitate intracellular mTOR trafficking in humans after exercise. The purpose of this study was to determine the effect of postexercise LEAA (4 g total EAAs, 1.6 g leucine) on acute MyoPS and mTORC1 translocation and signaling. Recreationally active men performed lower-body resistance exercise (5 × 8-10 leg press and leg extension) to volitional failure. Following exercise participants consumed LEAA (n = 8) or an isocaloric carbohydrate drink (PLA; n = 10). MyoPS was measured over 1.5-4 h of recovery by oral pulse of l-[ring-2H5]-phenylalanine. Phosphorylation of proteins in the mTORC1 pathway were analyzed via immunoblotting and mTORC1-LAMP2/WGA/Rheb colocalization via immunofluorescence microscopy. There was no difference in MyoPS between groups (LEAA = 0.098 ± 0.01%/h; PL = 0.090 ± 0.01%/h; P > 0.05). Exercise increased (P < 0.05) rpS6Ser240/244(LEAA = 35.3-fold; PLA = 20.6-fold), mTORSer2448(LEAA = 1.8-fold; PLA = 1.2-fold) and 4EBP1Thr37/46(LEAA = 1.5-fold; PLA = 1.4-fold) phosphorylation irrespective of nutrition (P > 0.05). LAT1 and SNAT2 protein expression were not affected by exercise or nutrient ingestion. mTOR-LAMP2 colocalization was greater in LEAA preexercise and decreased following exercise and supplement ingestion (P < 0.05), yet was unchanged in PLA. mTOR-WGA (cell periphery marker) and mTOR-Rheb colocalization was greater in LEAA compared with PLA irrespective of time-point (P < 0.05). In conclusion, the postexercise consumption of 4 g of LEAA maintains mTOR in peripheral regions of muscle fibers, in closer proximity to its direct activator Rheb, during prolonged recovery independent of differences in MyoPS or mTORC1 signaling compared with PLA ingestion. This intracellular localization of mTOR may serve to "prime" the kinase for future anabolic stimuli.NEW & NOTEWORTHY This is the first study to investigate whether postexercise leucine-enriched amino acid (LEAA) ingestion elevates mTORC1 translocation and protein-protein interactions in human skeletal muscle. Here, we observed that although LEAA ingestion did not further elevate postexercise MyoPS or mTORC1 signaling compared with placebo, mTORC1 peripheral location and interaction with Rheb were maintained. This may serve to "prime" mTORC1 for subsequent anabolic stimuli.

Effect of Local Anesthetic Versus Botulinum Toxin-A Injections for Myofascial Pain Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVE: Myofascial pain is a chronic pain disorder characterized by the presence of painful localized regions of stiff muscle and/or myofascial trigger points. Intramuscular myofascial trigger point injections are considered first-line treatments for myofascial pain. Common injectates include local anesthetics and botulinum toxin-A (BTX-A). The objective of this systematic review was to compare the effectiveness of local anesthetics and BTX-A on pain intensity in patients with myofascial pain. METHODS: A comprehensive systematic search of 3 databases, EMBASE, CENTRAL, and Medline was conducted. The search was comprised of words to describe "myofascial pain" and "injections." We performed a meta-analysis comparing local anesthetic and BTX-A injections across these follow-up week periods: 0 (immediately following the injection), 1 to 2, 3 to 4, 5 to 6, 7 to 8, 9 to 10, 11 to 12, 16, 18, 24 weeks with local anesthetics and BTX-A as subgroups. We also performed subgroup analyses comparing the effectiveness of local anesthetic injections and BTX-A injections at various muscle locations and comparing the effectives of single versus multiple injection sessions. RESULTS: In total, 33 studies were included. A qualitative analysis suggested that local anesthetics and BTX-A were inconsistently effective at mitigating pain across all follow-up periods. The meta-analyses revealed that local anesthetic injections were more effective than BTX-A at mitigating pain intensity. Multiple injection sessions of local anesthetics were more beneficial than a single session. CONCLUSIONS: Additional studies are needed to determine sources of heterogeneity mediating the observed differences in effectiveness of local anesthetic and BTX-A injections among the studies. Additional replicative studies are also needed to delineate the relative efficacy and effectiveness of local anesthetic and BTX-A injection. The quantitative results of this study suggest that patients overall experience more pain relief with local anesthetic injections.

Quantitative Ultrasound Using Texture Analysis of Myofascial Pain Syndrome in the Trapezius.

Objective-The objective of this study is to assess the discriminative ability of textural analyses to assist in the differentiation of the myofascial trigger point (MTrP) region from normal regions of skeletal muscle. Also, to measure the ability to reliably differentiate between three clinically relevant groups: healthy asymptomatic, latent MTrPs, and active MTrP. Methods-18 and 19 patients were identified with having active and latent MTrPs in the trapezius muscle, respectively. We included 24 healthy volunteers. Images were obtained by research personnel, who were blinded with respect to the clinical status of the study participant. Histograms provided first-order parameters associated with image grayscale. Haralick, Galloway, and histogram-related features were used in texture analysis. Blob analysis was conducted on the regions of interest (ROIs). Principal component analysis (PCA) was performed followed by multivariate analysis of variance (MANOVA) to determine the statistical significance of the features. Results-92 texture features were analyzed for factorability using Bartlett's test of sphericity, which was significant. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.94. PCA demonstrated rotated eigenvalues of the first eight components (each comprised of multiple texture features) explained 94.92% of the cumulative variance in the ultrasound image characteristics. The 24 features identified by PCA were included in the MANOVA as dependent variables, and the presence of a latent or active MTrP or healthy muscle were independent variables. Conclusion-Texture analysis techniques can discriminate between the three clinically relevant groups.