Evidence for an association of serum microanalytes and myofascial pain syndrome.

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. METHODS: This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann-Whitney test and Spearman's multivariate correlation were applied for all variables. The Spearman's analysis results were used to generate a standard correlation matrix and heat map matrix. RESULTS: Mean age of participants was 32 years (20-61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1-3 years, 14 (37%) 3-10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. CONCLUSION: Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS.

The Immediate Effect of Spinal Manipulation on Ball Velocity and Neuromuscular Function During an Instep Kick in Former Varsity Soccer Players: A Feasibility Study.

ABSTRACT: Corso, M, Liang, L, Tran, S, Howitt, S, Srbely, J, and Mior, SA. The immediate effect of spinal manipulation on ball velocity and neuromuscular function during an instep kick in former Varsity soccer players: a feasibility study. J Strength Cond Res 36(9): 2558-2565, 2022-Spinal manipulation (SM) has been shown to increase ball velocity (BV) in soccer players. Evidence suggests that SM modulates responses at spinal or cortical levels to enhance force production in asymptomatic populations. No studies have explored the underlying neuromuscular mechanisms contributing to changes in BV post-SM in soccer players. We assessed the feasibility of measuring change in BV and neuromuscular function after SM in former Varsity level soccer players with a pre-post study design. Three to 5 maximal instep kicks were performed before and after SM at the L3-5 level. Ball velocity was measured using high-speed camera. Activation of lower limb and trunk musculature was recorded with electromyography. Outcomes included ease of recruitment, scheduling and data capture, as well as expectation and perception of SM effect and adverse events (AE). Fifteen potential subjects were recruited over 1.5 months. Eleven were scheduled (24-31 years; 8 females, 3 males). Two subjects reported mild AE after maximal voluntary isometric contraction testing. A significant increase in BV (mean change: 1.75 m·s -1 [95% confidence interval: 0.5-3.0]) and a trend to increased peak-activation of knee extensors (90.7%) were observed post-SM. Findings suggest that our recruitment strategy and methodology are feasible in a larger trial with some modifications. Our preliminary findings support previous research by suggesting that increased BV may be mediated through increased activation of knee extensors during the kick. Our findings may offer additional insight into the underlying neuromuscular mechanisms contributing to immediate change in BV post-SM.

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.

The Acute Effect of Skin Preheating on Capsaicin-Induced Central Sensitization in Humans.

INTRODUCTION: Topical capsaicin is commonly employed to experimentally induce central sensitization (CS) in humans. While previous studies have investigated the effect of skin preheating on the sensitizing effect of capsaicin, no studies have compared the synergistic effect of skin preheating on the magnitude of sensitization via topical capsaicin within the first 30 minutes of application. We tested the hypothesis that skin preheating potentiates the sensitizing effect of topical capsaicin by evoking a larger region of secondary hyperalgesia vs. topical capsaicin alone. METHODS: Twenty young, healthy subjects each received topical capsaicin (Zostrix HP 0.075%) only (CAP), topical capsaicin with preheating (CAP + HEAT), and topical nonsensitizing placebo cream (CON) in a crossover design. Capsaicin and placebo creams were applied to a 50 cm2 area of the dorsal forearm. The CAP + HEAT session also included a 10-minute preheating session. Regions of secondary hyperalgesia were assessed using mechanical brush allodynia testing, and skin temperature was assessed via infrared thermography. Outcomes were normalized to baseline and compared at 10, 20, and 30 minutes after cream application. RESULTS: The CAP + HEAT session led to a significantly larger area of secondary hyperalgesia compared to the CAP session as measured by brush allodynia (CON: 0 ± 0 cm; CAP: 2.08 ± 0.45 cm; CAP + HEAT: 3.70 ± 0.46 cm; P < 0.05) and skin temperature (CON: -2.92% ± 0.03%; CAP: -0.63% ± 0.09%; CAP + HEAT: 2.50% ± 0.11%; ( of baseline) P < 0.05). CONCLUSION: Preheating amplifies the sensitizing effect of topical capsaicin within 30 minutes of application. The heat-capsaicin technique may be employed to assess differing magnitudes of CS induction and enables future studies investigating the development and progression of CS in humans.

A Survey of Physicians' Knowledge and Adherence to the Diagnostic Criteria for Fibromyalgia.

Objective: In 2010, Wolfe et al. demonstrated poor physician use of the 1990 fibromyalgia diagnostic criteria and proposed the 2010 criteria to address physician shortcomings. No follow-up studies have investigated whether physicians are using these criteria. The purpose of this study was to provide seminal data on physician knowledge and use of the fibromyalgia diagnostic criteria. Methods: This was an observational study. A questionnaire was distributed to a convenience sample of physicians who diagnose chronic pain conditions. Physician agreement was evaluated with statements testing their knowledge on the fibromyalgia criteria, and then intraclass correlations were calculated to determine the homogeneity of physicians' responses. We also determined whether physician knowledge was impacted by their specialist training and clinical experience. Results: Physician responses varied between correct and incorrect agreement on most questions. Physician specialist training was positively correlated with knowledge of the criteria. Physician knowledge overall was not comprehensive and was very poor for the 1990 and 2010 criteria. Fifty-one percent of physicians used a set of criteria in their practice, and 49% used their clinical acumen. Conclusions: Physicians do not have adequate and homogenous knowledge of the fibromyalgia diagnostic criteria. Approximately half of physicians did not adhere to the criteria. Poor knowledge and adherence to the criteria may increase diagnosis delays and misdiagnoses. Knowledge translation strategies should be implemented to address this problem.

Spinal Manipulative Therapy and Other Conservative Treatments for Low Back Pain: A Guideline From the Canadian Chiropractic Guideline Initiative.

OBJECTIVE: The objective of this study was to develop a clinical practice guideline on the management of acute and chronic low back pain (LBP) in adults. The aim was to develop a guideline to provide best practice recommendations on the initial assessment and monitoring of people with low back pain and address the use of spinal manipulation therapy (SMT) compared with other commonly used conservative treatments. METHODS: The topic areas were chosen based on an Agency for Healthcare Research and Quality comparative effectiveness review, specific to spinal manipulation as a nonpharmacological intervention. The panel updated the search strategies in Medline. We assessed admissible systematic reviews and randomized controlled trials for each question using A Measurement Tool to Assess Systematic Reviews and Cochrane Back Review Group criteria. Evidence profiles were used to summarize judgments of the evidence quality and link recommendations to the supporting evidence. Using the Evidence to Decision Framework, the guideline panel determined the certainty of evidence and strength of the recommendations. Consensus was achieved using a modified Delphi technique. The guideline was peer reviewed by an 8-member multidisciplinary external committee. RESULTS: For patients with acute (0-3 months) back pain, we suggest offering advice (posture, staying active), reassurance, education and self-management strategies in addition to SMT, usual medical care when deemed beneficial, or a combination of SMT and usual medical care to improve pain and disability. For patients with chronic (>3 months) back pain, we suggest offering advice and education, SMT or SMT as part of a multimodal therapy (exercise, myofascial therapy or usual medical care when deemed beneficial). For patients with chronic back-related leg pain, we suggest offering advice and education along with SMT and home exercise (positioning and stabilization exercises). CONCLUSIONS: A multimodal approach including SMT, other commonly used active interventions, self-management advice, and exercise is an effective treatment strategy for acute and chronic back pain, with or without leg pain.

The Effect of Abdominal Muscle Activation Techniques on Trunk and Lower Limb Mechanics During the Single-Leg Squat Task in Females.

CONTEXT: Females suffer 4 to 6 times more noncontact anterior cruciate ligament (ACL) injuries than males due to neuromuscular control deficits of the hip musculature leading to increases in hip adduction angle, knee abduction angle, and knee abduction moment during dynamic tasks such as single-leg squats. Lateral trunk displacement has been further related to ACL injury risk in females, leading to the incorporation of core strength/stability exercises in ACL preventative training programs. However, the direct mechanism relating lateral trunk displacement and lower limb ACL risk factors is not well established. OBJECTIVE: To assess the relationship between lateral trunk displacement and lower limb measures of ACL injury risk by altering trunk control through abdominal activation techniques during single-leg squats in healthy females. DESIGN: Interventional study setting: movement and posture laboratory. PARTICIPANTS: A total of 13 healthy females (21.3 [0.88] y, 1.68 [0.07] m, and 58.27 [5.46] kg). INTERVENTION: Trunk position and lower limb kinematics were recorded using an optoelectric motion capture system during single-leg squats under differing conditions of abdominal muscle activation (abdominal hollowing, abdominal bracing, and control), confirmed using surface electromyography. MAIN OUTCOME MEASURES: Lateral trunk displacement, peak hip adduction angle, peak knee abduction angle/moment, and average muscle activity from bilateral internal oblique, external oblique, and erector spinae muscles. RESULTS: No differences were observed for peak lateral trunk displacement, peak hip adduction angle, or peak knee abduction angle/moment. Abdominal hollowing and bracing elicited greater muscle activation than the control condition, and bracing was greater than hollowing in 4 of 6 muscles recorded. CONCLUSION: The lack of reduction in trunk, hip, and knee measures of ACL injury risk during abdominal hollowing and bracing suggests that these techniques alone may provide minimal benefit in ACL injury prevention training.

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.

A Survey of Healthcare Practitioners on Myofascial Pain Criteria.

OBJECTIVES: The goal of this study was to assess agreement on signs and symptoms of myofascial pain for chiropractors, physicians, and registered massage therapists. METHODS: 337 healthcare practitioners participated in the survey. The questionnaire probed clinician agreement with the chosen signs and symptoms using a 7-point agreement scale (1 = absolutely agree, 7 = absolutely disagree). Agreement was assessed using intraclass correlation within chiropractor, physician, and registered massage therapist groups and across all groups. Descriptive statistics, including mean response values, were used to assess which signs or symptoms were most often associated with myofascial pain. RESULTS: There was poor agreement within chiropractors, physicians, and registered massage therapists on the criteria that represent myofascial pain syndrome. Physicians and massage therapists were in agreement on 4 items and disagreed on 2 items. Chiropractors were in agreement on a different set of signs and symptoms relative to physicians and registered massage therapists, and they expressed neutrality on most statements in the questionnaire. Registered massage therapists were in most agreement amongst each other as a group (intraclass correlation coefficient [ICC] = 0.80) relative to chiropractors (ICC = 0.59) and physicians (ICC = 0.51). DISCUSSION: Our results suggest that there is a lack of agreement within and between healthcare practitioner groups on the signs and symptoms that define myofascial pain syndrome. We suggest the demonstrated variability in diagnostic knowledge be remedied through the establishment and universal use of official validated criteria. Future research should focus on developing criteria specific to myofascial pain syndrome. Finally, knowledge translation strategies may be implemented to increase clinician knowledge of available criteria.

A Comparison of the Sensitivity of Brush Allodynia and Semmes-Weinstein Monofilament Testing in the Detection of Allodynia Within Regions of Secondary Hyperalgesia in Humans.

BACKGROUND: Two of the most common Quantitative Sensory Techniques (QST) employed to detect allodynia include mechanical brush allodynia and Semmes-Weinstein monofilaments. However, their relative sensitivity at detecting allodynia is poorly understood. The purpose of this study was to compare the sensitivity of brush allodynia against Semmes-Weinstein monofilament technique for detecting allodynia within regions of secondary hyperalgesia in humans. METHODS: Twenty subjects (10 males, 10 females; 21.1 ± 0.9 years) were recruited and randomly allocated to allodynia or monofilament groups. Topical capsaicin (Zostrix 0.075%) was applied to a target region defined by C4-C7 dermatomes. Allodynia testing was performed at 0- (baseline) and 10 minutes postcapsaicin. The Semmes-Weinstein group assessed changes in skin sensitivity 8 cm inferior to target region and 2 cm lateral to the spinous process, while brush allodynia was employed to detect the point inferior to the target region where subjects reported changes in skin sensitivity. The distance (cm) from this point to the inferior border of the target region was termed the Allodynia Score. RESULTS: Statistically significant increases in the Allodynia Score were observed at 10 minutes postcapsaicin compared to baseline (P < 0.001). No differences in monofilament scores were observed between 10 minutes postcapsaicin and baseline (P = 0.125). Brush allodynia also demonstrated superior sensitivity, detecting allodynia in 100% of cases compared to 60% in the Semmes-Weinstein group. CONCLUSION: Brush allodynia is more sensitive than Semmes-Weinstein monofilaments for detecting mechanical allodynia in regions of secondary hyperalgesia. Brush allodynia may be preferred over Semmes-Weinstein monofilaments for clinical applications requiring reliable detection of allodynia.

The Treatment of Neck Pain-Associated Disorders and Whiplash-Associated Disorders: A Clinical Practice Guideline.

OBJECTIVE: The objective was to develop a clinical practice guideline on the management of neck pain-associated disorders (NADs) and whiplash-associated disorders (WADs). This guideline replaces 2 prior chiropractic guidelines on NADs and WADs. METHODS: Pertinent systematic reviews on 6 topic areas (education, multimodal care, exercise, work disability, manual therapy, passive modalities) were assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and data extracted from admissible randomized controlled trials. We incorporated risk of bias scores in the Grading of Recommendations Assessment, Development, and Evaluation. Evidence profiles were used to summarize judgments of the evidence quality, detail relative and absolute effects, and link recommendations to the supporting evidence. The guideline panel considered the balance of desirable and undesirable consequences. Consensus was achieved using a modified Delphi. The guideline was peer reviewed by a 10-member multidisciplinary (medical and chiropractic) external committee. RESULTS: For recent-onset (0-3 months) neck pain, we suggest offering multimodal care; manipulation or mobilization; range-of-motion home exercise, or multimodal manual therapy (for grades I-II NAD); supervised graded strengthening exercise (grade III NAD); and multimodal care (grade III WAD). For persistent (>3 months) neck pain, we suggest offering multimodal care or stress self-management; manipulation with soft tissue therapy; high-dose massage; supervised group exercise; supervised yoga; supervised strengthening exercises or home exercises (grades I-II NAD); multimodal care or practitioner's advice (grades I-III NAD); and supervised exercise with advice or advice alone (grades I-II WAD). For workers with persistent neck and shoulder pain, evidence supports mixed supervised and unsupervised high-intensity strength training or advice alone (grades I-III NAD). CONCLUSIONS: A multimodal approach including manual therapy, self-management advice, and exercise is an effective treatment strategy for both recent-onset and persistent neck pain.

The effect of experimental pain on motor training performance and sensorimotor integration.

Experimental pain is known to affect neuroplasticity of the motor cortex as well as motor performance, but less is known about neuroplasticity of somatosensory processing in the presence of pain. Early somatosensory evoked potentials (SEPs) provide a mechanism for investigating alterations in sensory processing and sensorimotor integration (SMI). The overall aim of this study was to investigate the interactive effects of acute pain, motor training, and sensorimotor processing. Two groups of twelve participants (N = 24) were randomly assigned to either an intervention (capsaicin cream) or placebo (inert lotion) group. SEP amplitudes were collected by stimulation of the median nerve at baseline, post-application and post-motor training. Participants performed a motor sequence task while reaction time and accuracy data were recorded. The amplitude of the P22-N24 complex was significantly increased following motor training for both groups F(2,23) = 3.533, p < 0.05, while Friedman's test for the P22-N30 complex showed a significant increase in the intervention group [χ(2) (df = 2, p = 0.016) = 8.2], with no significant change in the placebo group. Following motor training, reaction time was significantly decreased for both groups F(1,23) = 59.575, p < 0.01 and overall accuracy differed by group [χ(2) (df = 3, p < 0.001) = 19.86], with post hoc testing indicating that the intervention group improved in accuracy following motor training [χ(2) (df = 1, p = 0.001) = 11.77] while the placebo group had worse accuracy [χ(2) (df = 1, p = 0.006) = 7.67]. The improved performance in the presence of capsaicin provides support for the enhancement of knowledge acquisition with the presence of nontarget stimuli. In addition, the increase in SEP peak amplitudes suggests that early SEP changes are markers of SMI changes accompanying motor training and acute pain.

Ultrasound-based assessment of the expression of inflammatory markers in the rectus femoris muscle of rats.

Ultrasonographic characteristics of skeletal muscles are related to their health status and functional capacity, but they still provide limited information on muscle composition during the inflammatory process. It has been demonstrated that an alteration in muscle composition or structure can have disparate effects on different ranges of ultrasonogram pixel intensities. Therefore, monitoring specific clusters or bands of pixel intensity values could help detect echotextural changes in skeletal muscles associated with neurogenic inflammation. Here we compare two methods of ultrasonographic image analysis, namely, the echointensity (EI) segmentation approach (EI banding method) and detection of selective pixel intensity ranges correlated with the expression of inflammatory regulators using an in-house developed computer algorithm (r-Algo). This study utilized an experimental model of neurogenic inflammation in segmentally linked myotomes (i.e., rectus femoris (RF) muscle) of rats subjected to lumbar facet injury. Our results show that there were no significant differences in RF echotextural variables for different EI bands (with 50- or 25-pixel intervals) between surgery and sham-operated rats, and no significant correlations among individual EI band pixel characteristics and protein expression of inflammatory regulators studied. However, mean numerical pixel values for the pixel intensity ranges identified with the proprietary r-Algo computer program correlated with protein expression of ERK1/2 and substance P (both 86-101-pixel ranges) and CaMKII (86-103-pixel range) in RF, and were greater (p < 0.05) in surgery rats compared with their sham-operated counterparts. Our findings indicate that computer-aided identification of specific pixel intensity ranges was critical for ultrasonographic detection of changes in the expression of inflammatory mediators in neurosegmentally-linked skeletal muscles of rats after facet injury.

Immediate effects of spinal manipulative therapy on regional antinociceptive effects in myofascial tissues in healthy young adults.

OBJECTIVE: The purpose of this study was to investigate if spinal manipulative therapy (SMT) can evoke immediate regional antinociceptive effects in myofascial tissues by increasing pressure pain thresholds (PPTs) over myofascial trigger points in healthy young adults. METHODS: A total of 36 participants (19 men, 17 women; age, 28.0 [5.3] years; body mass index, 26.5 [5.7] kg/m(2)) with clinically identifiable myofascial trigger points in the infraspinatus and gluteus medius muscles were recruited from the University of Guelph, Ontario, Canada. Participants were randomly allocated to 2 groups. Participants in the test group received chiropractic SMT targeted to the C5-C6 spinal segment. Participants in the control group received sham SMT. The PPT was recorded from the right infraspinatus and gluteus medius muscles at baseline (preintervention) and 1, 5, 10, and 15 minutes postintervention. RESULTS: Three participants were disqualified, resulting in a total of 33 participants analyzed. Significant increases in the PPT (decreased pain sensitivity) were observed in the test infraspinatus group when compared with test gluteus medius, control infraspinatus, and control gluteus medius groups (P < .05). No significant differences in PPT were observed at any time point when comparing test gluteus medius, control infraspinatus, and control gluteus medius groups (P > .05). CONCLUSIONS: This study showed that SMT evokes short-term regional increases in PPT within myofascial tissues in healthy young adults.

The reliability of pressure pain threshold in individuals with low back or neck pain: a systematic review.

Background and Objective: Low-back and neck pain affect a great number of individuals worldwide. The pressure pain threshold has the potential to be a useful quantitative measure of mechanical pain in a clinical setting, if it proves to be reliable in this population. The objectives of this systematic review are to: (1) analyze the literature evaluating the reliability of pressure pain threshold (PPT) measurements in the assessment of neck and low-back pain, (2) summarize the evidence from these studies, and (3) characterize the limitations of PPT measurement. Databases and Data Treatment: Relevant literature from PubMed and the Web of Science electronic databases were screened in a 3-step process according to inclusion/exclusion criteria. Relevant studies were assessed for risk of bias using the Quality Appraisal of Reliability Studies (QAREL) tool, and results of all studies were summarized and tabulated. Results: Of 922 citations identified, 11 studies were deemed relevant for critical appraisal, and 8 studies were deemed to have low risk-of bias. Intra-rater reliability, reported in all studies (n = 637) and inter-rater reliability, reported in 2 studies (n = 200) were consistently reported to be good to excellent (ICC 0.75-0.99 and ICC 0.81-0.90, respectively). Studies were also found to have significant variation in PPT measurement procedures. Conclusions: Though intra- and inter-rater reliability was found to be high in all studies, the variation in PPT measurement protocols could affect validity and absolute reliability. As such, it is recommended that standard guidelines be developed for clinical use.

A model for personalized diagnostics for non-specific low back pain: the role of the myofascial unit.

Low back pain (LBP) is the leading cause of disability worldwide. Most LBP is non-specific or idiopathic, which is defined as symptoms of unknown origin without a clear specific cause or pathology. Current guidelines for clinical evaluation are based on ruling out underlying serious medical conditions, but not on addressing underlying potential contributors to pain. Although efforts have been made to identify subgroups within this population based on response to treatment, a comprehensive framework to guide assessment is still lacking. In this paper, we propose a model for a personalized mechanism-based assessment based on the available evidence that seeks to identify the underlying pathologies that may initiate and perpetuate central sensitization associated with chronic non-specific low back pain (nsLBP). We propose that central sensitization can have downstream effects on the "myofascial unit", defined as an integrated anatomical and functional structure that includes muscle fibers, fascia (including endomysium, perimysium and epimysium) and its associated innervations (free nerve endings, muscle spindles), lymphatics, and blood vessels. The tissue-level abnormalities can be perpetuated through a vicious cycle of neurogenic inflammation, impaired fascial gliding, and interstitial inflammatory stasis that manifest as the clinical findings for nsLBP. We postulate that our proposed model offers biological plausibility for the complex spectrum of clinical findings, including tissue-level abnormalities, biomechanical dysfunction and postural asymmetry, ecological and psychosocial factors, associated with nsLBP. The model suggests a multi-domain evaluation that is personalized, feasible and helps rule out specific causes for back pain guiding clinically relevant management. It may also provide a roadmap for future research to elucidate mechanisms underlying this ubiquitous and complex problem.

Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice.

In the context of the electroacupuncture (EA) neurobiological mechanisms, we have previously demonstrated the involvement of formyl peptide receptor 2 (FPR2/ALX) in the antihyperalgesic effect of EA. The present study investigated the involvement of peripheral FPR2/ALX in the antihyperalgesic effect of EA on inflammatory cytokines levels, oxidative stress markers and antioxidant enzymes in an animal model of persistent inflammatory pain. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2/10 Hz, ST36-SP6, 20 minutes) for 4 consecutive days. From the first to the fourth day after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or saline before EA. Levels of inflammatory cytokines (TNF, IL-6, IL-4 and IL-10), antioxidant enzymes (catalase and superoxide dismutase), oxidative stress markers (TBARS, protein carbonyl, nitrite/nitrate ratio), and myeloperoxidase activity were measured in paw tissue samples. As previously demonstrated, i.pl. injection of the FPR2/ALX antagonist prevented the antihyperalgesic effect induced by EA. Furthermore, animals treated with EA showed higher levels of IL-10 and catalase activity in the inflamed paw, and these effects were prevented by the antagonist WRW4. EA did not change levels of TNF and IL-6, SOD and MPO activity, and oxidative stress markers. Our work demonstrates that the antihyperalgesic effect of EA on CFA-induced inflammatory pain could be partially associated with higher IL-10 levels and catalase activity, and that these effects may be dependent, at least in part, on the activation of peripheral FPR2/ALX.

Ultrasonographic assessment of skeletal muscles after experimentally induced neurogenic inflammation (facet injury) in rats.

This study set out to examine ultrasonographic attributes of non-neurosegmentally (pectoral-forelimb) and neurosegmentally linked (hindlimb) myotomes in an experimental model that leads to neurogenic inflammation in segmentally linked myotomes, and to evaluate quantitative correlations among ultrasonographic attributes of the muscles, relative content of various inflammatory mediators, and nociceptive thresholds (hot and mechanical) in rats. Twelve male Wistar Kyoto rats were randomly divided into two equinumerous groups: surgery group, in which the left lumbar (L4-L6) facet joints were compressed for 3 min with modified Kelly forceps under general anesthesia, and sham-operated rats. All ultrasonograms were obtained with the Vevo 2100 Visual Sonic scanner connected to a 24-MHz transducer at four different time points: pre-surgery and 7, 14, and 21 days after surgical procedures. Digital ultrasonographic images of quadriceps femoris, hamstring, and pectoral-brachial muscle groups were analyzed using a polygonal meter region of interest placed on the largest cross-sectional area of the muscles displayed in Image ProPlus® analytical software to compute numerical pixel values and pixel heterogeneity (standard deviation of mean pixel values). On day 21, pain behavior tests (hot plate and von Frey) were performed and then all animals were euthanized. Protein expression of inflammatory mediators in biceps brachii and rectus femoris muscles was measured by Western blot. The most prominent differences in muscle echotextural attributes between the two subsets of rats occurred 14 days post-surgery in pectoral-brachial and quadriceps femoris muscles. The expression of calcitonin-gene-related peptide was directly related to both echotextural variables only in biceps brachii (pixel intensity: r = 0.65, P = 0.02; and heterogeneity: r = 0.66, P = 0.02, respectively). Our findings have revealed the occurrence of echotextural changes in skeletal muscles of rats during myositis; however, the accumulation of inflammatory mediators and the outcomes of sensory tests did not relate to the changes in first-order echotextural characteristics of affected hindlimb muscles.

Impaired Lymphatic Drainage and Interstitial Inflammatory Stasis in Chronic Musculoskeletal and Idiopathic Pain Syndromes: Exploring a Novel Mechanism.

A normal functioning lymphatic pump mechanism and unimpaired venous drainage are required for the body to remove inflammatory mediators from the extracellular compartment. Impaired vascular perfusion and/or lymphatic drainage may result in the accumulation of inflammatory substances in the interstitium, creating continuous nociceptor activation and related pathophysiological states including central sensitization and neuroinflammation. We hypothesize that following trauma and/or immune responses, inflammatory mediators may become entrapped in the recently discovered interstitial, pre-lymphatic pathways and/or initial lymphatic vessels. The ensuing interstitial inflammatory stasis is a pathophysiological state, created by specific pro-inflammatory cytokine secretion including tumor necrosis factor alpha, interleukin 6, and interleukin 1b. These cytokines can disable the local lymphatic pump mechanism, impair vascular perfusion via sympathetic activation and, following transforming growth factor beta 1 expression, may lead to additional stasis through direct fascial compression of pre-lymphatic pathways. These mechanisms, when combined with other known pathophysiological processes, enable us to describe a persistent feed-forward loop capable of creating and maintaining chronic pain syndromes. The potential for concomitant visceral and/or vascular dysfunction, initiated and maintained by the same feed-forward inflammatory mechanism, is also described.

Experimentally induced spine osteoarthritis in rats leads to neurogenic inflammation within neurosegmentally linked myotomes.

Naturally occurring spine osteoarthritis is clinically associated with the manifestation of chronic inflammatory muscle (myofascial) disease. The purpose of this study was to investigate the causal association between experimentally induced spine osteoarthritis and neurogenic inflammatory responses within neurosegmentally linked myotomes. Wistar Kyoto rats were randomly assigned to spine facet compression surgery (L4-L6) or sham surgery. Animals exposed to facet compression surgery demonstrated radiographic signs of facet-osteoarthritis (L4-L6 spinal levels) and sensory changes (allodynia, thermal hyperalgesia) at 7, 14 and 21 days post-intervention, consistent with the induction of central sensitization; no radiologic or sensory changes were observed after sham surgery. Increased levels of proinflammatory biomarkers including substance P (SP), calcitonin gene related peptide (CGRP), protease-activated receptor-2 (PAR2) and calcium/calmodulin dependent protein kinase II (CaMKII) were observed post-surgery within neurosegmentally-linked rectus femoris (L2-L5) muscle when compared to the non-segmentally linked biceps brachii (C4-C7) muscle; no differences were observed between muscles in the sham surgery group. These findings offer novel insight into the potential role of spine osteoarthritis and neurogenic inflammatory mechanisms in the pathophysiology of chronic inflammatory muscle (myofascial) disease.