Effects of Transcranial Direct Current Stimulation (t-DCS) of the Cerebellum on Pain Perception and Endogenous Pain Modulation: a Randomized, Monocentric, Double-Blind, Sham-Controlled Crossover Study.

Accumulating evidence demonstrates a role of the cerebellum in nociception. Some studies suggest that this is mediated via endogenous pain modulation. Here, we used t-DCS to test the effects of modulation of cerebellar function on nociception and endogenous pain modulation. Anodal, cathodal, and sham cerebellar t-DCS were investigated in a cross-over design in 21 healthy subjects. The nociceptive flexor (RIII) reflex, conditioning pain modulation (CPM), and offset analgesia (OA) paradigms were used to assess endogenous pain modulation. Somatosensory evoked potentials (SEPs) and pain ratings were used to assess supraspinal nociception and pain perception, respectively. No significant t-DCS effects were detected when including all t-DCS types and time points (baseline, 0, 30, 60 min post t-DCS) in the analysis. Exploratory analysis revealed an increased RIII reflex size immediately after cathodal t-DCS (compared to sham, P = 0.046, η2p = 0.184), in parallel with a trend for a decrease in electrical pain thresholds (P = 0.094, η2p = 0.134), and increased N120 SEP amplitudes 30 min after cathodal compared to anodal t-DCS (P = 0.007, η2p = 0.374). OA was increased after anodal compared to sham stimulation (P = 0.023, η2p = 0.232). Exploratory results suggested that cathodal (inhibitory) cerebellar t-DCS increased pain perception and reduced endogenous pain inhibition while anodal (excitatory) t-DCS increased endogenous pain inhibition. Results are principally compatible with activation of endogenous pain inhibition by cerebellar excitation. However, maybe due to limited t-DCS skull penetration, effects were small and unlikely to be clinically significant.

The Contribution of Psychological Factors to Inter-Individual Variability in Conditioned Pain Modulation Is Limited in Young Healthy Subjects.

Conditioned pain modulation (CPM) describes the decrease in pain perception of a test stimulus (TS) when presented together with a heterotopic painful conditioning stimulus (CS). Inter-individual differences in CPM are large and have been suggested to reflect differences in endogenous pain modulation. In a previous analysis, we demonstrated that in young, healthy participants, inter-individual differences account for about one-third of CPM variance, with age and sex together explaining only 1%. Here, we investigated if psychological factors explain significant amounts of inter-individual variance in CPM. Using the same dataset as before, we performed both cross-sectional (n = 126) and repeated measures (n = 52, 118 observations) analysis and the corresponding variance decompositions, using results of psychological questionnaires assessing depression, trait anxiety and pain catastrophizing. Psychological factors did not significantly predict CPM magnitude, neither directly nor when interactions with the CPM paradigm were assessed; however, the interaction between depression and the paradigm approached significance. Variance decomposition showed that the interaction between depression and the CPM paradigm explained an appreciable amount of variance (3.0%), but this proportion seems small when compared to the residual inter-individual differences (35.4%). The main effects of the psychological factors and the interactions of anxiety or catastrophizing with the CPM paradigm are explained at <0.1% each. These results show that the contribution of psychological factors to inter-individual CPM differences in healthy participants is limited and that the large inter-individual variability in the CPM effect remains largely unexplained.

Prairie strips' effect on transport of antimicrobial resistance indicators in poultry litter.

Poultry litter is a valuable nutrient resource for agricultural production but is also a potential source for introducing antibiotic resistance genes (ARGs) and litter-associated bacteria (LAB) to the environment. Prairie strips have been demonstrated as an effective conservation practice to improve environmental quality in agroecosystems. This research aims to assess prairie strips' potential for reducing the transport of LAB and ARGs in runoff after litter application. Plot-scale rainfall simulations were performed using a replicated block design, with soil and surface runoff samples taken during the rainfall event. Microbial taxa and ARGs were characterized in the litter, soil, and water samples. In plots with litter application, LAB and ARGs were mainly detected in runoff, with very low detection in soils. Detection of ARGs in runoff, irrespective of strip installations, is consistent with previous observations of litter as a source of antimicrobial resistance (AMR) risks. The effectiveness of prairie strips to remove LAB and ARGs varied. In two of the three prairie strip plots, fewer AMR indicators were detected relative to control plots, suggesting that the prairie strips can potentially reduce these risks. In one plot, which was also associated with increased flow rate, we observed increased AMR indicators despite the installation of a prairie strip. Our observations highlight the need to prioritize understanding of soil properties even within the same site. Although we show that prairie strips can potentially reduce AMR risks, further research is needed to better understand the influence of rainfall timing, soil, and litter characteristics.

Antibiotic resistance gene dissipation in soil microcosms amended with antibiotics and swine manure.

The use of antibiotics in animal agriculture has exacerbated the presence of both antibiotic resistance genes (ARGs) and residual antibiotics excreted in animal manure. Field application of this manure is a common practice because its nutrient rich material can benefit crop growth. However, this practice can also introduce antibiotics and ARGs into nonagricultural settings. The integration of prairie buffer strips within and at the edge of crop fields is a potential management solution to reduce concentrations of ARGs commonly transported via water runoff and infiltration. An incubation experiment was conducted to investigate the fate of ARGs in directly manured crop field soils and the surrounding affected prairie strip soils. Row crop and prairie strip soils sampled from three sites received either an antibiotic spike and swine manure addition or a control water addition. The concentrations of select ARGs were then monitored over a 72-d period. Although soil vegetation and site location were not observed to influence ARG dissipation, the select genes did display different half-lives from one another. For example, tetM demonstrated the fastest dissipation of the genes quantified (average half-life, 5.18 d). Conversely, sul1 did not conform to the first-order linear regression kinetics used to describe the other investigated genes and was highly abundant in control prairie strip soils. The quantified half-lives of these select ARGs are comparable to previous studies and can inform monitoring and mitigative efforts aimed at reducing the spread of ARGs in the environment.

A Randomized Sham-Controlled Cross-Over Study on the Short-Term Effect of Non-Invasive Cervical Vagus Nerve Stimulation on Spinal and Supraspinal Nociception in Healthy Subjects.

OBJECTIVE: The aim of the present study was to test the effects of vagus nerve stimulation (VNS) on the descending pain inhibition, quantified by the nociceptive flexor (RIII) reflex and the conditioned pain modulation (CPM) paradigm, and on supraspinal nociceptive responses, assessed by pain intensity and unpleasantness ratings and late somatosensory evoked potentials (SEPs), in healthy subjects. BACKGROUND: Non-invasive vagus nerve stimulation (nVNS) showed promising effects on headache and pain treatment. Underlying mechanisms are only incompletely understood but may include the activation of the descending pain inhibitory system and/or the modification of emotional responses to pain. METHODS: Twenty-seven adult, healthy, and pain-free subjects participated in this double-blind cross-over study conducted at a university research center. They received 4 minutes of cervical nVNS or sham stimulation in randomized order. RIII reflexes, pain ratings, and SEPs were assessed before, during, and 5, 15, 30, and 60 minutes after nVNS/sham stimulation, followed by CPM testing. The primary outcome was the nVNS effect on the RIII reflex size. Three subjects were excluded after the preparatory session (before randomization), 1 subject was excluded after outlier analysis, leaving 23 for analysis. RESULTS: RIII reflex areas were 917.1 ± 563.8 µV × ms (mean ± SD) before, 952.4 ± 467.4 µV × ms during and 929.2 ± 484.0 µV × ms immediately after nVNS and 858.4 ± 489.2 µV × ms before, 913.9 ± 539.7 µV × ms during and 862.4 ± 476.0 µV × ms after sham stimulation, revealing no differences between the immediate effects of nVNS and sham stimulation (F [3,66]  = 0.67, P = .574). There also were no effects of nVNS over sham on RIII reflex areas up to 60 minutes after nVNS (F [1.7,37.4]  = 1.29, P = .283). Similarly, there was no statistically significant effect of nVNS on pain intensity ratings and thresholds, RIII reflex thresholds, late SEP amplitudes, and the CPM effect, compared to sham. Pain unpleasantness ratings statistically significantly decreased from 4.4 ± 2.4 (NRS 0-10) to 4.1 ± 2.5 during nVNS compared to sham stimulation (F [1,22]  = 8.74, P = .007), but there were no longer lasting effects (5-60 minutes after stimulation). CONCLUSIONS: The present study does not support an acute effect of nVNS on descending pain inhibition, pain intensity perception or supraspinal nociception in healthy adults. However, there was a small effect on pain unpleasantness during nVNS, suggesting that nVNS may preferentially act on affective, not somatosensory pain components.