There is a Lack of Clinical Homogeneity in Lower-Limb Tendinopathy Trials: A Scoping Review.

OBJECTIVE: It is unclear if clinical trials of treatments for lower-limb tendinopathies include clinically homogeneous participant populations (an assumption for pooling in meta-analyses). We assessed the recruitment setting and participant characteristics used in randomized controlled trials (RCTs) that were investigating any treatment for lower-limb tendinopathies. DESIGN: Scoping review. METHODS: We conducted a systematic literature search in the PubMed, Embase, Cochrane CENTRAL, and Web of Science databases. All RCTs that were investigating treatments for lower-limb tendinopathies in an adult population (≥18 years) were eligible for inclusion. At least 2 authors conducted independent screening and selection of full-text papers, and extracted data from included studies. RESULTS: Of 18 341 records, 342 RCTs (21 897 participants) were eligible for inclusion and data extraction. The most common diagnoses were plantar fasciopathy (n = 195, 57%), Achilles tendinopathy (n = 82, 24%), and patellar tendinopathy (n = 41, 12%). Secondary care (n = 144, 42%) was the most reported recruitment setting, followed by an open setting (n = 44, 13%). In 93 (27%) RCTs, the recruitment setting was not described. We found high heterogeneity in participant characteristics (eg, symptom duration, age, body mass index, and the Victorian Institute of Sport Assessment [VISA] questionnaire score) within and between recruitment settings. CONCLUSION: Our results question whether clinical homogeneity can be adequately assumed in clinical trials of lower-limb tendinopathies due to the lack of clear reporting of the recruitment setting and the variability within and between recruitment settings of key participant characteristics. These findings threaten assumptions for meta-analyses in lower-limb tendinopathies. J Orthop Sports Phys Ther 2024;54(1):1-10. Epub 5 December 2023. doi:10.2519/jospt.2023.11722.

Do adolescents with Osgood-Schlatter display nociplastic pain manifestations compared to controls: A cross-sectional study.

OBJECTIVES: Osgood-Schlatter disease is an overuse musculoskeletal pain condition. The pain mechanism is considered nociceptive, but no studies have investigated nociplastic manifestations. This study investigated pain sensitivity and inhibition evaluated through exercise-induced hypoalgesia in adolescents with and without Osgood-Schlatter. DESIGN: Cross-sectional study. METHODS: Adolescents underwent a baseline assessment comprising clinical history, demographics, sports participation, and pain severity rated (0-10) during a 45-second anterior knee pain provocation test, consisting of an isometric single leg squat. Pressure pain thresholds were assessed bilaterally at the quadriceps, tibialis anterior muscle, and the patella tendon before and after a three-minute wall squat. RESULTS: Forty-nine adolescents (27 Osgood-Schlatter, 22 controls) were included. There were no differences in the exercise-induced hypoalgesia effect between Osgood-Schlatter and controls. Overall, an exercise-induced hypoalgesia effect was detected at the tendon only in both groups with a 48 kPa (95 % confidence interval 14 to 82) increase in pressure pain thresholds from before to after exercise. Controls had higher pressure pain thresholds at the patellar tendon (mean difference 184 kPa 95 % confidence interval 55 to 313), tibialis anterior (mean difference 139 kPa 95 % confidence interval 24 to 254), and rectus femoris (mean difference 149 kPa 95 % confidence interval 33 to 265). Higher anterior knee pain provocation severity was associated with lower exercise-induced hypoalgesia at the tendon (Pearson correlation = 0.48; p = 0.011) in participants with Osgood-Schlatter. CONCLUSIONS: Adolescents with Osgood-Schlatter display increased pain sensitivity locally, proximally, and distally but similar endogenous pain modulation compared to healthy controls. Greater Osgood-Schlatter severity appears to be associated with less efficient pain inhibition during the exercise-induced hypoalgesia paradigm.

The impact of prolonged experimental neck pain on walking stability and gait kinematics - A parallel-group study.

BACKGROUND: Neck pain is a common problem in the general population, and movement adaptations are a natural response to pain. Previous studies have reported reduced trunk rotation during walking in those suffering from clinical neck pain. However, it is unknown how soon after the onset of pain, movement adaptations are adopted. This study investigated the effect of prolonged experimental neck pain four days after pain onset on gait kinematics during walking. METHODS: Forty healthy participants were randomized to receive injections of nerve-growth-factor or a control injection of isotonic saline into the right splenius capitis muscle at the end of days 0 and 2. Participants performed two walking tasks, walking and walking while reading on a smartphone, on days 0, 4, and 15. Gait kinematics, spatiotemporal parameters, and gait stability were measured using Xsens Awinda. FINDINGS: The nerve-growth-factor group reported increased neck pain intensity (median VAS 17.5 [IQR: 2.75-25.75]) on day 4 compared to day 0 and day 15. No pain intensity changes between days were reported for the isotonic-group. For gait kinematics, a main effect of the task was identified, showing that during the smartphone condition, participants had shorter stride lengths and reduced RoM for the trunk, hip, knee, and ankle compared to normal waking (P < 0.006). INTERPRETATION: Walking while reading on a smartphone, but not mild neck muscle pain, caused changes in the gait kinematics compared to normal walking without neck pain. This finding suggests that movement alterations during walking are not an early feature of prolonged experimental neck pain.

Repeated Injections of Low-Dose Nerve Growth Factor (NGF) in Healthy Humans Maintain Muscle Pain and Facilitate Ischemic Contraction-Evoked Pain.

OBJECTIVE: Nerve growth factor (NGF) is essential for generating and potentiating pain responses. This double-blinded crossover study assessed NGF-evoked pain in healthy humans after repeated NGF injections in the tibialis anterior (TA) muscle compared with control injections of isotonic saline. SUBJECTS: Twenty healthy subjects participated in two experimental phases; each consisted of seven sessions over 21 days. METHODS: At day 0, day 2, and day 4, a low-dose NGF (1 µg) was injected. Data on daily self-reported muscle pain (using a Likert scale) were collected. Data on pressure pain thresholds (PPTs), pain evoked by nonischemic and ischemic muscle contractions (using a numerical rating scale [NRS]), pressure pain detection (PDT), and pain tolerance thresholds (PTTs) to cuff algometry were recorded before day 0 and at 1, 2, 4, 7, 10, and 21 days after the first injection. Temporal summation of pain (TSP) and conditioned pain modulation (CPM) were recorded to assess central pain mechanisms. RESULTS: Likert scores remained elevated for 9 days after NGF injection (P<0.05). PPTs at the TA muscle were decreased at day 1 until day 7 after NGF injection compared with day 0 (P=0.05). In subjects presenting with NGF-induced muscle hyperalgesia, pain NRS scores evoked by nonischemic contractions were higher after NGF injection at day 4 and day 7 (P<0.04) compared with the control condition. At all time points, higher pain NRS scores were found with ischemic compared with nonischemic contractions (P<0.05). The pain NRS after ischemic contractions was elevated following prolonged NGF hyperalgesia at day 7 compared with the control condition and day 0 (P<0.04). The PDT, PTT, TSP, and CPM remained unchanged during the period of NGF-induced hyperalgesia. CONCLUSIONS: Repeated low-dose NGF injections maintain muscle pain and potentiate pain evoked by ischemic contractions during prolonged NGF hyperalgesia.

Nerve growth factor-induced muscle hyperalgesia facilitates ischaemic contraction-evoked pain.

BACKGROUND: Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo-sensitive channels affecting muscle pain sensitivity. This double-blinded crossover study in healthy humans assessed contraction-evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24 hr after five distributed NGF injections (1 µg, 4 cm interval) compared with control injections (isotonic-saline). METHODS: Twenty-one subjects participated in two experimental phases, each including five sessions over 7 days, with a gap of 4 weeks in-between. Muscle pain intensity evoked with daily functional tasks (Likert scale score) was collected using a paper diary. Pain intensity evoked by ischaemic and non-ischaemic contractions numerical rating scale (NRS) was collected at Day0 and Day1. Pressure pain thresholds (PPTs) on the TA were recorded before (Day0), 3 hr, 1, 3, and 7 days post-injection, and after the ischaemic-contractions and post-cuff deflation at Day0 and Day1. RESULTS: Increased Likert scores of pain were present for 7 days after NGF compared to control injections (p < .05). Higher NRS pain scores of ischaemic-contractions were seen when contracting the muscle injected with NGF compared to baseline (p = .003) and control (p = .012). Pain during non-ischaemic contractions was not significantly affected by NGF injections. Decreased PPTs were found at 3 hr, Day1 and Day3 post-injection (p < .05) in both conditions. Compared with pre-contractions, PPTs were increased following ischaemic contractions at Day0 (p < .05) and Day1 (p < .05) in both conditions. CONCLUSION: This study showed that ischaemic contraction-evoked pain was facilitated in an NGF-sensitized muscle. SIGNIFICANCE: Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC3 and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)-sensitized muscle compared with non-ischaemic contractions and in the non-sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre-sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.

Investigation of biomarkers alterations after an acute tissue trauma in human trapezius muscle, using microdialysis.

Alterations in muscle milieu are suggested as important activity of peripheral drive in patients with chronic musculoskeletal pain (CMP). Microdialysis (MD) has been used in monitoring altered metabolic response pattern in muscles. However, the insertion of MD probe causes a local tissue trauma. Whether and how metabolites in trapezius muscle are affected by acute tissue trauma is unknown. Hence, this study investigated the metabolic response and nociceptive reaction of the tissue following MD probe insertion in patients with CMP and healthy individuals. Fifty-nine patients and forty pain-free volunteers were recruited. Pressure pain thresholds (PPTs) were obtained at the trapezius and tibialis muscles. Pain questionnaires determined the levels of pain related aspects. MD (20 kDa cut-off) was performed in the trapezius and samples were collected within 40 min. Interstitial concentration of the metabolites was analyzed by a two-way-mixed-ANOVA. The metabolic response pattern changed over time and alterations in the level of metabolites could be seen in both CMP and healthy controls. Pain questionnaires and pain intensities manifested clinical aspects of pain closely to what CMP patients describe. Analyzing metabolites due to acute tissue trauma by aid of MD may be a useful model to investigate altered metabolic response effect in CMP.