The purpose of the study was to examine an association of repetitive subconcussive head impacts with changes in plasma neurofilament light (NF-L) levels following 10 bouts of controlled soccer heading. In this randomized control trial, 37 healthy adult soccer players were randomly assigned into either a heading (n = 19) or kicking-control group (n = 18). The heading group executed 10 headers with soccer balls projected at a velocity of 25 mph over 10 min. Plasma samples were obtained at pre-heading baseline, 0 h, 2 h, and 24 h post-heading. The kicking-control group followed the same protocol with 10 kicks. Plasma NF-L was measured using ultrasensitive single-molecule array technology. Data from 34 subjects were eligible for analysis (heading n = 18 and kicking n = 16). Ten subconcussive head impacts induced a gradual increase in plasma NF-L expression for the heading group (β = 0.0297, standard error [SE] = 0.01, p = 0.0049), whereas there was no significant time effect for the kicking-control group. A follow-up analysis revealed that a significant difference appeared at 24 h post-heading (3.68 ± 0.30 pg/mL) compared with pre-heading (3.12 ± 0.29 pg/mL, p = 0.0013; Cohen's d = 1.898). At the 24 h post-heading time-point, the plasma NF-L level for the heading group was significantly higher than that of the kicking-control group with an estimated mean difference of 0.66 pg/mL (SE = 0.22, p = 0.0025). The data suggest that the increased level of plasma NF-L was driven by repetitive subconcussive head impacts and required longer than 2 h after the head impacts for the increase to be detected. Plasma NF-L levels may serve as an objective marker to monitor acute axonal burden from subconcussive head impacts.

The CB cannabinoid agonist LY2828360 lacked both toxicity and efficacy in a clinical trial for osteoarthritis. Whether LY2828360 suppresses neuropathic pain has not been reported, and its signaling profile is unknown. In vitro, LY2828360 was a slowly acting but efficacious G protein-biased CB agonist, inhibiting cAMP accumulation and activating extracellular signal-regulated kinase 1/2 signaling while failing to recruit arrestin, activate inositol phosphate signaling, or internalize CB2 receptors. In wild-type (WT) mice, LY2828360 (3 mg/kg per day i.p. × 12 days) suppressed chemotherapy-induced neuropathic pain produced by paclitaxel without producing tolerance. Antiallodynic efficacy of LY2828360 was absent in CB knockout (KO) mice. Morphine (10 mg/kg per day i.p. × 12 days) tolerance developed in CBKO mice but not in WT mice with a history of LY2828360 treatment (3 mg/kg per day i.p. × 12 days). LY2828360-induced antiallodynic efficacy was preserved in WT mice previously rendered tolerant to morphine (10 mg/kg per day i.p. × 12 days), but it was absent in morphine-tolerant CBKO mice. Coadministration of LY2828360 (0.1 mg/kg per day i.p. × 12 days) with morphine (10 mg/kg per day × 12 days) blocked morphine tolerance in WT but not in CBKO mice. WT mice that received LY2828360 coadministered with morphine exhibited a trend ( = 0.055) toward fewer naloxone-precipitated jumps compared with CBKO mice. In conclusion, LY2828360 is a slowly signaling, G protein-biased CB agonist that attenuates chemotherapy-induced neuropathic pain without producing tolerance and may prolong effective opioid analgesia while reducing opioid dependence. LY2828360 may be useful as a first-line treatment in chemotherapy-induced neuropathic pain and may be highly efficacious in neuropathic pain states that are refractive to opioid analgesics.

No abstract

IMPORTANCE Subconcussive head impacts have emerged as a complex public health concern. The oculomotor system is sensitive to brain trauma; however, neuro-ophthalmologic response to subconcussive head impacts remains unclear.OBJECTIVE To examine whether subconcussive head impacts cause impairments in neuro-ophthalmologic function as measured by the King-Devick test (KDT) and oculomotor function as measured by the near point of convergence. DESIGN, SETTING, AND PARTICIPANTSIn this randomized clinical trial, adult soccer players were randomized into either a heading group or kicking (control) group. The heading group executed 10 headers with soccer balls projected at a speed of 25 mph. The kicking-control group followed the same protocol but with 10 kicks. Peak linear and rotational head accelerations were assessed with a triaxial accelerometer. The KDT speed and error and near point of convergence were assessed at baseline (preheading or prekicking) and at 0, 2, and 24 hours after heading or kicking.EXPOSURES Ten soccer-ball headings or kicks. MAIN OUTCOMES AND MEASURESThe primary outcome was the group-by-time interaction of KDT speed at 0 hours after heading or kicking. The secondary outcomes included KDT speed at 2 hours and 24 hours after heading or kicking, KDT error, and near point of convergence.RESULTS A total of 78 individuals enrolled (heading group, n = 40; kicking-control group, n = 38). Eleven individuals (heading group: 4 women; mean [SD] age, 22.5 [1.0] years; kicking-control group, 3 women and 4 men; mean [SD] age, 20.9 [1.1] years) voluntarily withdrew from the study. Data from 67 participants with a mean (SD) age of 20.6 (1.7) years were eligible for analysis (heading, n = 36; kicking-control, n = 31). Mean (SD) peak linear accelerations and peak rotational accelerations per impact for the heading group were 33.2 (6.8) g and 3.6 (1.4) krad/s 2 , respectively. Conversely, soccer kicking did not induce a detectable level of head acceleration. Both groups showed improvements in KDT speed (heading group: 0

Astrocyte-enriched marker, S100B, shows promise for gauging the severity of acute brain trauma, and understanding subconcussive effects will advance its utility in tracking real-time acute brain damage. The aim of the study was to investigate whether serum S100B elevations were associated with frequency and magnitude of subconcussive head impacts in adolescents. This prospective cohort study of 17 high-school football players consisted of the following 12 time points: pre-season baseline, 5 in-season pre-post games, and post-season. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA) and peak rotational (PRA) head accelerations from every practice and game. During the 5 games, players wore chest-strap heart-rate monitors to estimate players' excess post-exercise oxygen consumption (EPOC), accounting for physical exertion effects. At each time point, blood samples were obtained and assessed for S100B and creatine kinase levels to account for astrocyte damage/activation and muscle damage, respectively. Using k -means clustering on the impact data, players were categorized into high- or low-impact group. Two players withdrew during the first month of the study. A total of 156 blood samples from 15 players were assessed for S100B and creatine kinase levels and included in the analysis. A median value of 596 head impacts from 15 players were recorded during all practices and games in a season. S100B levels were significantly elevated in all post-game measures compared with the respective pre-game values (median-increase, 0.022 μg/L; interquartile-range, 0.011–0.043 μg/L, p < 0.05 for all games). Greater acute S100B increases were significantly associated with greater impact frequency, sum of PLA and PRA, with negligible contributions from physical exertion and muscle damage effects. The high-impact group exhibited greater increases in serum S100B levels at post-games than the low-impact group (high vs. low, 0.043 ± 0.035 μg/L vs. 0.019 ± 0.017 μg/L, p = 0.002). The degree of acute S100B increases was correlated with subconcussive head impact exposure, suggesting that acute astrocyte damage may be induced in an impact-dependent manner. Acute changes in serum S100B levels may become a useful tool in monitoring real-time brain damage in sports.