Intramuscular injection of nerve growth factor (NGF) causes muscle hyperalgesia without immediate pain. This double-blinded, randomized study assessed pain and muscle hypersensitivity after a single-site bolus NGF injection (5 mg) compared with 5 spatially distributed, low-dose NGF injections (1 mg, 4 cm distance) into the tibialis anterior (TA) muscles in 20 healthy subjects. Injection pain was rated on a visual analog scale. Reports of muscle pain with functional tasks (Likert scale score) and the presence of spontaneous pain were collected daily by using a diary. Pressure pain threshold (PPT), overall pain intensity (numerical rating scale), and pain areas following the TA contraction were collected at baseline; 3 hours; and 1, 3, 7, 14, and 21 days postinjection. Low immediate visual analog scale scores were associated with both injection protocols. Likert scale scores showed moderate pain intensities but no spontaneous pain, until day 12, for both injection protocols (P < .05). Reduced PPTs at the 5-and 1-mg injection sites were found after 3 hours, lasting until day 7 (P < .05). The 1-mg injection provoked decreased PPTs at day 1 (P = .036) at the proximal injection site and at day 1 (P = .02) and day 3 (P = .01) at the distal injection site. The TA muscle contraction resulted in larger pain areas and higher numerical rating scale scores at day 3 for the distributed injections compared with the single-site injection (P < .001). Perspective: Spatially distributed low-dose NGF injections induced prolonged pain, mechanical muscle hypersensitivity, and enlarged contraction-evoked pain areas. These features mirror some clinical muscle pain conditions in which diffuse pain areas and muscle hypersensitivity are present during the activities of daily living. Low-dose NGF injections may be useful for further studies of prolonged pain conditions.

Numerous non-antibiotic feed additives (alternatives to antibiotics, ATAs) have been marketed, but few have been evaluated under uniform testing conditions modelling commercial flocks. We compared 24 ATA treatments and the ionophorous coccidiostat narasin against a diet without any feed additives. Feed conversion ratio and body weight gain were registered from day 0 to 28 in Ross 308 chickens housed on litter floor. The chickens were challenged with Eimeria spp., and cecal Clostridium perfringens (CP) counts were investigated. Active components from all ATA classes had a positive impact on intestinal health or production performance. Whereas narasin had a strong CP-reducing effect in combination with performance-promoting impact, only two ATA treatments achieved significantly beneficial effects on CP counts as well as feed conversion during the time span following Eimeria challenge. Active components present in these two treatments include a Bacillus subtilis probiotic strain, short- and medium-chain fatty acids and Saccharomyces cerevisiae components. Different ATA classes had beneficial impact during distinct rearing phases and on specific performance targets, suggesting that optimizing combinations and use of active components can make ATAs even more useful tools in broiler rearing without the use of in-feed antimicrobials. Further studies of promising ATAs and ATA combinations are required.

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&lt;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&lt;0.04) compared with the control condition. At all time points, higher pain NRS scores were found with ischemic compared with nonischemic contractions (P&lt;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&lt;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.

This systematic review aimed to describe the imaging characteristics of Osgood‐Schlatter (OSD) compared with controls and imaging findings over time. A systematic search was conducted in Embase, CINAHL, and PubMed from inception until July 2021. Forty studies were eligible and included based on inclusion criteria on OSD diagnosis, the number of patients, and imaging outcomes. In patients with OSD, but not controls, findings were soft‐tissue swelling of the cartilage and infrapatellar bursa, tendon changes, increased Doppler flow, and fragmentation of the secondary ossification center. Follow‐up studies reported improvements over time, but some identified persistent tendon thickening and/or ossicles. Adults with OSD generally present with free ossicles. Findings were inconsistent on whether different morphometric features were altered in OSD compared to controls. OSD patients were classified within the early stages of tibial tuberosity maturation. This review documents that OSD presents with tissue alterations that do not appear in controls or the patient's asymptomatic knee. Notably, a large portion had tendon involvement, and ossicles seem to be associated with residual symptoms after maturation. Standard imaging of adolescents with OSD needs to be carefully considered when determining if tissue alterations are related to disease progression or part of the normal maturation.

Background This study investigated (a) if a prolonged noxious stimulus (24‐hr topical capsaicin) in healthy adults would impair central pain inhibitory and facilitatory systems measured as a reduction in conditioned pain modulation (CPM) and enhancement of temporal summation of pain (TSP) and (b) if acute pain relief or exacerbation (cooling and heating the capsaicin patch) during the prolonged noxious stimulus would affect central pain modulation. Methods Twenty‐eight participants (26.2 ± 1.0 years; 12 women) wore a transdermal 8% capsaicin patch on the forearm for 24 hr. Data were collected at baseline (Day 0), 1 hr, 3 hr, Day 1 (post‐capsaicin application) and Day 3/4 (post‐capsaicin removal) that included capsaicin‐evoked pain intensity, heat pain thresholds (HPTs), TSP (10 painful cuff pressure stimuli on leg) and CPM (cuff pressure pain threshold on the leg prior vs. during painful cuff pressure conditioning on contralateral leg). After 3 hr, cold (12°C) and heat (42°C) stimuli were applied to the capsaicin patch to transiently increase and decrease pain intensity. Results Participants reported moderate pain scores at 1 hr (2.5 ± 2.0), 3 hr (3.7 ± 2.4), and Day 1 (2.4 ± 1.8). CPM decreased 3‐hr post‐capsaicin (p = .001) compared to Day 0 and remained diminished while the capsaicin pain score was reduced (0.4 ± 0.7, p < .001) and increased (6.6 ± 2.2, p < .001) by patch cooling and heating. No significant differences occurred for CPM during patch cooling or heating compared to initial 3HR; however, CPM during patch heating was reduced compared with patch cooling (p = .01). TSP and HPT did not change. Conclusions This prolonged experimental pain model is useful to provide insight into subacute pain conditions and may provide insight into the transition from acute to chronic pain. Significance During the early hours of a prolonged noxious stimulus in healthy adults, CPM efficacy was reduced and did not recover by temporarily removing the ongoing pain indicating a less dynamic neuroplastic process.