Temperature sensation has a strong impact on animal behavior and is necessary for animals to avoid exposure to harmful temperatures. It is now well known that thermoTRP (Transient Receptor Potential) channels in thermosensory neurons detect a variable range of temperature stimuli. However, little is known about how a range of temperature information is relayed and integrated in the neural circuits. Here, we show novel temperature integration between two warm inputs via Drosophila TRPA channels, TRPA1 and Pyrexia (Pyx). The internal AC (Anterior Cell) thermosensory neurons, which express TRPA1, detect warm temperatures and mediate temperature preference behavior. We found that the AC neurons were activated twice when subjected to increasing temperatures. The first response was at ~25°C via TRPA1 channel, which is expressed in the AC neurons. The second response was at ~27°C via the 2nd antennal segments, indicating that the 2nd antennal segments are involved in the detection of warm temperatures. Further analysis reveals that pyx-Gal4 expressing neurons have synapses on the AC neurons and that mutation of pyx eliminates the second response of the AC neurons. These data suggest that AC neurons integrate both their own TRPA1-dependent temperature responses and a Pyx-dependent temperature response from the 2nd antennal segments. Our data reveal the first identification of temperature integration, which combines warm temperature information from peripheral to central neurons and provides the possibility that temperature integration is involved in the plasticity of behavioral outputs.
Background: Continuous epidural infusion (CEI) is commonly used for labour analgesia, but concerns over potential motor block, second-stage labour complications, and ineffective analgesia in late labour have prompted examining intermittent epidural bolus (IEB) as an alternative. However, evidence comparing these modalities is conflicting. The meta-analysis evaluates the analgesic efficacy of CEI vs IEB. Methods: Databases were searched for trials comparing CEI to IEB for labour analgesia. The two co-primary outcomes were risk of breakthrough pain and difference in area under the curve (AUC) for pain scores during the first 4 h postepidural initiation. Local anaesthetic consumption, maternal outcomes (i.e. delivery mode, labour duration, and maternal satisfaction), and side-effects of epidural analgesia were also evaluated. Results were pooled using randomeffects modelling. Trial sequential analysis (TSA) was used to evaluate evidence reliability. Results: Twenty-seven studies (3133 patients) were analysed. Compared with CEI, IEB decreased risk of breakthrough pain by 38% (risk ratio [95% confidence interval {CI}] of 0.62 [0.48, 0.81]; P¼0.0004; I 2 ¼47%; 1164 patients) and reduced AUC of pain during the 4 h interval by 32.9% (mean difference [95% CI] of e16.7 mm h À1 [e18.9, e14.4]; P<0.0001; 1638 patients). Intermittent epidural bolus enhanced maternal satisfaction, shortened labour duration, decreased motor block, and reduced local anaesthetic consumption. The difference between the two groups was not statistically significant for epidural side-effects or mode of delivery. The TSA indicated adequate power for reliable inferences. Conclusions: Intermittent epidural bolus provides improved labour pain control during the first 4 h after epidural initiation with less breakthrough pain. Moderate-to high-quality evidence of intermittent epidural bolus superiority support its use as a safe and effective continuous epidural infusion alternative for labour analgesia.
Summary Anterior cruciate ligament reconstruction can cause moderate to severe acute postoperative pain. Despite advances in our understanding of knee innervation, consensus regarding the most effective regional anaesthesia techniques for this surgical population is lacking. This network meta‐analysis compared effectiveness of regional anaesthesia techniques used to provide analgesia for anterior cruciate ligament reconstruction. Randomised trials examining regional anaesthesia techniques for analgesia following anterior cruciate ligament reconstruction were sought. The primary outcome was opioid consumption during the first 24 h postoperatively. Secondary outcomes were: rest pain at 0, 6, 12 and 24 h; area under the curve of pain over 24 h; and opioid‐related adverse effects and functional recovery. Network meta‐analysis was conducted using a frequentist approach. A total of 57 trials (4069 patients) investigating femoral nerve block, sciatic nerve block, adductor canal block, local anaesthetic infiltration, graft‐donor site infiltration and systemic analgesia alone (control) were included. For opioid consumption, all regional anaesthesia techniques were superior to systemic analgesia alone, but differences between regional techniques were not significant. Single‐injection femoral nerve block combined with sciatic nerve block had the highest p value probability for reducing postoperative opioid consumption and area under the curve for pain severity over 24 h (78% and 90%, respectively). Continuous femoral nerve block had the highest probability (87%) of reducing opioid‐related adverse effects, while local infiltration analgesia had the highest probability (88%) of optimising functional recovery. In contrast, systemic analgesia, local infiltration analgesia and adductor canal block were each poor performers across all analgesic outcomes. Regional anaesthesia techniques that target both the femoral and sciatic nerve distributions, namely a combination of single‐injection nerve blocks, provide the most consistent analgesic benefits for anterior cruciate ligament reconstruction compared with all other techniques but will most likely impair postoperative function. Importantly, adductor canal block, local infiltration analgesia and systemic analgesia alone each perform poorly for acute pain management following anterior cruciate ligament reconstruction.
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