Luke J Heales

Reliability of the Conditioned Pain Modulation Paradigm to Assess Endogenous Inhibitory Pain Pathways

BACKGROUND Conditioned pain modulation paradigms are often used to assess the diffuse noxious inhibitory control (DNIC) system. DNICs provide one of the main supraspinal pain inhibitory pathways and are impaired in several chronic pain populations. Only one previous study has examined the psychometric properties of the conditioned pain modulation technique and this study did not evaluate intersession reliability. OBJECTIVES To evaluate and compare the intra- and intersession reliability of two conditioned pain modulation paradigms using different conditioning stimuli, and to determine the time course of conditioned pain inhibition following stimulus removal. METHODS An electronic pressure transducer was used to determine the pressure-pain threshold at the knee during painful conditioning of the opposite hand using the ischemic arm test and the cold pressor test. Assessments were completed twice on one day and repeated once approximately three days later. RESULTS The two conditioning stimuli resulted in a similar increase in the pressure-pain threshold at the knee, reflecting presumed activation of the DNIC system. Intrasession intraclass correlation coefficients for the cold pressor (0.85) and ischemic arm tests (0.75) were excellent. The intersession intraclass correlation coefficient for the cold pressor test was good (0.66) but was poor for the ischemic arm test (-0.4). Inhibition of the pressure-pain threshold remained significant at 10 min following conditioning, but returned to baseline by 15 min. CONCLUSIONS Within-session reliability of DNIC assessment using conditioned pain modulation paradigms was excellent, but the applicability of assessing pain modulation over multiple sessions was influenced by the conditioning stimulus. The cold pressor test was the superior technique.

Sensory and motor deficits exist on the non-injured side of patients with unilateral tendon pain and disability—implications for central nervous system involvement: a systematic review with meta-analysis

Introduction Tendinopathy manifests as activity-related tendon pain with associated motor and sensory impairments. Tendon tissue changes in animals present in injured as well as contralateral non-injured tendon. This review investigated evidence for bilateral sensory and motor system involvement in unilateral tendinopathy in humans. Methods A comprehensive search of electronic databases, and reference lists using keywords relating to bilateral outcomes in unilateral tendinopathy was undertaken. Study quality was rated with the Epidemiological Appraisal Instrument and meta-analyses carried out where appropriate. Analysis focused on comparison of measures in the non-symptomatic side of patients against pain-free controls. Results The search revealed 5791 studies, of which 20 were included (117 detailed reviews, 25 met criteria). There were 17 studies of lateral epicondylalgia (LE) and one each for patellar, Achilles and rotator cuff tendinopathy. Studies of LE were available for meta-analysis revealing the following weighted pooled mean deficits: pressure pain thresholds (−144.3 kPa; 95% CI −169.2 to −119.2 p<0.001), heat pain thresholds (−1.2°C; 95% CI −2.1 to −0.2, p<0.001), cold pain thresholds (3.1°C; 95% CI 1.8 to 4.4, p<0.001) and reaction time (37.8 ms; 95% CI 24.8 to 50.7, p<0.001). Discussion Deficits in sensory and motor systems present bilaterally in unilateral tendinopathy. This implies potential central nervous system involvement. This indicates that rehabilitation should consider the contralateral side of patients. Research of unilateral tendinopathy needs to consider comparison against pain-free controls in addition to the contralateral side to gain a complete understanding of sensory and motor features.

UNDERSTANDING TENDON PAIN MECHANISMS THROUGH A SYSTEMATIC REVIEW OF WIDESPREAD MANIFESTATIONS OF UNILATERAL TENDINOPATHY

Introduction Tendinopathy is a clinical condition within or around the tendon that is thought to arise from high volume repetitive overuse, causing microtrauma.1 The local changes at the tissue have been well documented and include disorganisation of the collagen bundles, an increase in ground substance, and deformation of the tenocyte nuclei,2 leading to clinical signs and symptoms. To date there has been a concentrated focus on the local tendon pathology—however the potentially widespread systemic effects on the pain, motor, and sensory systems of which there is nascent information are poorly understood. The purpose of this systematic review was to investigate the prevalence of widespread changes in patients with unilateral tendinopathy. Methods A thorough search strategy including three electronic databases (Medline—via Ovid, PubMed, and Scopus) and references list were searched to February 2012 for English language papers relating to widespread manifestations in unilateral tendinopathy when compared to healthy controls. Two independent investigators assessed the quality of the included papers using the Epidemiology Appraisal Instrument.3 Data relating to population and methodology as well as the mean and SD for the outcomes of pressure pain threshold (PPT), cold pain threshold (CPT), heat pain threshold (HPT), grip strength (GS), reaction time (RT) and speed of movement (SoM) were extracted. Point estimates of effect for pooled data were calculated by a meta-analysis of differences between non-affected sites in those with unilateral tendinopathy compared to control participants. Results Overall, 5420 studies were identified from the search strategy, with 248 extracted for a detailed analysis and a total of 25 included within the review. Of the 25 included studies, there were 3 animal studies, 18 lateral epicondylalgia (LE), 2 patella tendinopathy, 1 Achilles tendinopathy, and 1 rotator cuff tendinopathy. Only LE had multiple studies that could be subjected to meta-analyses, with six studying PPT, three HPT and CPT, and two RT and SoM. Comparing the non-affected side of unilateral tendinopathy with the non-dominant or left side in healthy controls, mean differences were significantly lower for PPT (−144.34 kPa; 95% CI CI −169.52 to −119.16, p<0.001), HPT (1.13°C; 95% CI −1.83 to −0.44, p=0.001), and SoM (−20.71 cm/s; 95% CI −27.47 to −13.95, p<0.001), whereas it was significantly higher for CPT (3.09°C; 95% CI 1.80 to 4.38, p<0.001) and RT (35.08 ms; 95% CI 28.49 to 41.67, p<0.001). GS was significantly reduced (−21.43 N; 95% CI; −29.70 to −13.16; p<0.001), however there was significant heterogeneity (p<0.001), requiring caution in interpreting this result. Discussion This systematic review and meta-analyses demonstrates widespread manifestations in unilateral tendinopathy, mainly from studies of LE and requiring evaluation for tendinopathy at other sites. These results are concordant with evidence of bilateral deficits in other unilateral musculoskeletal conditions (eg, carpal tunnel syndrome,4 unilateral wrist pain5). It is not possible to determine if these deficits preceded or were a consequence of the unilateral condition. In any event, the presence of widespread changes in measures of pain and sensorimotor function in human studies imply that there are abnormal central nervous system processing. We propose that further study of these widespread changes might lead to better outcomes through improved management strategies.

Massage induces an immediate, albeit short-term, reduction in muscle stiffness

Using ultrasound shear wave elastography, the aims of this study were: (a) to evaluate the effect of massage on stiffness of the medial gastrocnemius (MG) muscle and (b) to determine whether this effect (if any) persists over a short period of rest. A 7‐min massage protocol was performed unilaterally on MG in 18 healthy volunteers. Measurements of muscle shear elastic modulus (stiffness) were performed bilaterally (control and massaged leg) in a moderately stretched position at three time points: before massage (baseline), directly after massage (follow‐up 1), and following 3 min of rest (follow‐up 2). Directly after massage, participants rated pain experienced during the massage. MG shear elastic modulus of the massaged leg decreased significantly at follow‐up 1 (−5.2 ± 8.8%, P = 0.019, d = −0.66). There was no difference between follow‐up 2 and baseline for the massaged leg (P = 0.83) indicating that muscle stiffness returned to baseline values. Shear elastic modulus was not different between time points in the control leg. There was no association between perceived pain during the massage and stiffness reduction (r = 0.035; P = 0.89). This is the first study to provide evidence that massage reduces muscle stiffness. However, this effect is short lived and returns to baseline values quickly after cessation of the massage.

Achilles and patellar tendinopathy display opposite changes in elastic properties: A shear wave elastography study

To compare tendon elastic and structural properties of healthy individuals with those with Achilles or patellar tendinopathy. Sixty‐seven participants (22 Achilles tendinopathy, 17 patellar tendinopathy, and 28 healthy controls) were recruited between March 2015 and March 2016. Shear wave velocity (SWV), an index of tissue elastic modulus, and tendon thickness were measured bilaterally at mid‐tendon and insertional regions of Achilles and patellar tendons by an examiner blinded to group. Analysis of covariance, adjusted for age, body mass index, and sex was used to compare differences in tendon thickness and SWV between the two tendinopathy groups (relative to controls) and regions. Tendon thickness was included as a covariate for analysis of SWV. Compared to controls, participants with Achilles tendinopathy had lower SWV at the distal insertion (Mean difference MD; 95% CI: −1.56; −2.49 to −0.62 m/s; P < .001) and greater thickness at the mid‐tendon (MD 0.19; 0.05‐0.33 cm; P = .007). Compared to controls, participants with patellar tendinopathy had higher SWV at both regions (MD 1.25; 0.40‐2.10 m/s; P = .005) and greater thickness proximally (MD 0.17; 0.06‐0.29 cm; P = .003). Compared to controls, participants with Achilles and patellar tendinopathy displayed lower Achilles tendon elastic modulus and higher patellar tendon elastic modulus, respectively. More research is needed to explore whether maturation, aging, or chronic load underlie these findings and whether current management programs for Achilles and patellar tendinopathy need to be tailored to the tendon.

Diagnostic Ultrasound Imaging for Lateral Epicondylalgia: A Case-Control Study.

INTRODUCTION Lateral epicondylalgia (LE) is clinically diagnosed as pain over the lateral elbow that is provoked by gripping. Usually, LE responds well to conservative intervention; however, those who fail such treatment require further evaluation, including musculoskeletal ultrasound. Previous studies of musculoskeletal ultrasound have methodological flaws, such as lack of assessor blinding and failure to control for participant age, sex, and arm dominance. The purpose of this study was to assess the diagnostic use of blinded ultrasound imaging in people with clinically diagnosed LE compared with that in a control group matched for age, sex, and arm dominance. METHODS Participants (30 with LE and 30 controls) underwent clinical examination as the criterion standard test. Unilateral LE was defined as pain over the lateral epicondyle, which was provoked by palpation, resisted wrist and finger extension, and gripping. Controls without symptoms were matched for age, sex, and arm dominance. Ultrasound investigations were performed by two sonographers using a standardized protocol. Grayscale images were assessed for signs of tendon pathology and rated on a four-point ordinal scale. Power Doppler was used to assess neovascularity and rated on a five-point ordinal scale. RESULTS The combination of grayscale and power Doppler imaging revealed an overall sensitivity of 90% and specificity of 47%. The positive and negative likelihood ratios for combined grayscale and power Doppler imaging were 1.69 and 0.21, respectively. CONCLUSIONS Although ultrasound imaging helps confirm the absence of LE, when findings are negative for tendinopathic changes, the high prevalence of tendinopathic changes in pain-free controls challenges the specificity of the measure. The validity of ultrasound imaging to confirm tendon pathology in clinically diagnosed LE requires further study with strong methodology.

Is synergistic organisation of muscle coordination altered in people with lateral epicondylalgia? A case–control study

BACKGROUND Lateral epicondylalgia is a common musculoskeletal disorder and is associated with deficits in the motor system including painful grip. This study compared coordination of forearm muscles (muscle synergies) during repeated gripping between individuals with and without lateral epicondylalgia. METHODS Twelve participants with lateral epicondylalgia and 14 controls performed 15 cyclical repetitions of sub-maximal (20% maximum grip force of asymptomatic arm), pain free dynamic gripping in four arm positions: shoulder neutral with elbow flexed to 90° and shoulder flexed to 90° with elbow extended both with forearm pronated and neutral. Muscle activity was recorded from extensor carpi radialis brevis/longus, extensor digitorum, flexor digitorum superficialis/profundus, and flexor carpi radialis, with intramuscular electrodes. Muscle synergies were extracted using non-negative matrix factorisation. FINDINGS Analysis of each position and participant, demonstrated that two muscle synergies accounted for >97% of the variance for both groups. Between-group differences were identified after electromyography patterns of the control group were used to reconstruct the patterns of the lateral epicondylalgia group. A greater variance accounted for was identified for the controls than lateral epicondylalgia (p=0.009). This difference might be explained by an additional burst of flexor digitorum superficialis electromyography during grip release in many lateral epicondylalgia participants. INTERPRETATION These data provide evidence of some differences in synergistic organisation of activation of forearm muscles between individuals with and without lateral epicondylalgia. Due to study design it is not possible to elucidate whether changes in the coordination of muscle activity during gripping are associated with the cause or effect of lateral epicondylalgia.

Patellar and Achilles tendinopathies are predominantly peripheral pain states: a blinded case control study of somatosensory and psychological profiles

Study design Case–control design. Background Tendinopathy is characterised by pain on tendon loading. In persistent cases of upper limb tendinopathy, it is frequently associated with central nervous system sensitisation, whereas less commonly linked in the case of persistent lower limb tendinopathies. Objectives Compare somatosensory and psychological profiles of participants with persistent patellar (PT) and Achilles tendinopathies (AT) with pain-free controls. Methods A comprehensive battery of Quantitative Sensory Testing (QST) was assessed at standardised sites of the affected tendon and remotely (lateral elbow) by a blinded assessor. Participants completed the Victorian Institute of Sports Assessment, a health-related quality of life questionnaire, the Hospital Anxiety and Depression Scale and the Active Australia Questionnaire. Independent t-test and analysis of covariance (sex-adjusted and age-adjusted) were performed to compare groups. Results Participants with PT and AT did not exhibit differences from controls for the QST at the remote site, but there were differences at the affected tendon site. Compared with controls, participants with PT displayed significantly lower pressure pain threshold locally at the tendon (p=0.012) and fewer single limb decline squats before pain onset, whereas participants with AT only displayed fewer single heel raises before pain onset, but this pain was of a higher intensity. Conclusion PT and AT appear to be predominantly local not widespread pain states related to loading of tendons without significant features of central sensitisation. Level of evidence Level 4.

Forearm muscle activity is modified bilaterally in unilateral lateral epicondylalgia: A case-control study

Lateral epicondylalgia (LE) is associated with a reduced wrist extensor muscle activity and altered biomechanics. This study compared the coordination between forearm muscles during gripping in individuals with LE and pain‐free controls. Intramuscular electrodes recorded myoelectric activity from extensor carpi radialis brevis/longus (ECRB/ECRL), extensor digitorum communis (EDC), flexor digitorum superficialis/profundus (FDS/FDP), and flexor carpi radialis (FCR), bilaterally, in 15 participants with unilateral LE and 15 pain‐free controls. Participants performed a gripping task at 20% maximum force in four arm positions. The contribution of each muscle was expressed as a proportion of the summed electromyography of all muscles. In individuals with LE, ECRB contributed less to total electromyography in the symptomatic arm but not the asymptomatic arm than pain‐free controls. The contribution of EDC and FDP to total electromyography was greater in both the symptomatic and asymptomatic arm of the LE group, than pain‐free controls. No other differences were observed between groups. Subtle differences in muscle activation were present with differing arm positions. These findings indicate forearm muscle activity is modified in LE. It is unknown whether this is cause or effect. Changes in the asymptomatic side may imply involvement of central mechanisms.

Isometric exercise above but not below an individual’s pain threshold influences pain perception in people with lateral epicondylalgia

Objective:To examine the acute effects of isometric exercise of different intensities on pain perception in individuals with chronic lateral epicondylalgia. Materials and Methods:Participants performed 3 experimental tasks completed in a randomized order on separate days: control (no exercise) and isometric wrist extension (10×15 s) at load 20% below (infrathreshold), and 20% above (suprathreshold) an individual’s pain threshold. Self-reported pain intensity (11-point numeric rating scales), pressure pain threshold, and pain-free grip were assessed by a blinded examiner before, immediately after, and 30 minutes after task performance. Relation analysis between pain ratings and clinical variables, including pain and disability and kinesiophobia was performed. Results:Twenty-four individuals with unilateral lateral epicondylalgia of median 3-month duration participated. Pain intensity during contraction was significantly higher during suprathreshold exercise than infrathreshold exercise (mean difference in numeric rating scale 1.0; 95% confidence interval, 0.4-1.5; P=0.002). Pain intensity during suprathreshold exercise was significantly correlated with pain and disability (R=0.435, P=0.034) and kinesiophobia (R=0.556, P=0.005). Pain intensity was significantly higher immediately after performance of suprathreshold exercise, compared with infrathreshold exercise (P=0.01) and control (P<0.001) conditions, whereas infrathreshold exercise and control conditions were comparable. Thirty minutes later, pain levels remained significantly higher for suprathreshold exercise compared with infrathreshold exercise (P=0.043). Pressure pain threshold and pain-free grip showed no significant effects of time, condition, or time×condition (P>0.05). Discussion:Individuals with lateral epicondylalgia demonstrated increased pain intensity after an acute bout of isometric exercise performed at an intensity above, but not below, their individual pain threshold. Further investigation is needed to determine whether measurement of an individual’s exercise induced pain threshold may be important in reducing symptom flares associated with exercise.