Motor-sparing peripatellar plexus block provides noninferior block duration and complete block area of the peripatellar region compared with femoral nerve block: a randomized, controlled, noninferiority study.

BACKGROUND: Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers. METHODS: The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded. RESULTS: The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was - 1.24 (95% CI, -2.81 - 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (Pnoninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block. CONCLUSION: Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020).

Sleep characteristics and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: The CABLE study.

INTRODUCTION: This study tested the self-reported sleep characteristics associated with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in cognitively intact older adults. METHODS: The linear and non-linear regression analyses were conducted in 736 cognitively normal participants (mean [standard deviation; SD] age, 62.3 [10.5] years, range 40 to 88 years, 59% female) who had measurements of cerebrospinal fluid (CSF) amyloid beta (Aß) and tTau proteins and sleep characteristics, after adjusting for age, gender, education, apolipoprotein E gene (APOE) ε4 status, and general cognition. RESULTS: Greater daytime sleepiness was associated with higher CSF indicators of amyloid deposition in female patients. No significant associations were revealed for CSF tTau proteins after Bonferroni correction. A U-shaped relationship was revealed for nocturnal sleep habits, such that those with insufficient or excessive nocturnal sleep duration had greater CSF biomarkers of amyloid deposition (the reflection range: bedtime: around 10:00 p.m. and sleep duration: 6.0 to 6.5 hours). DISCUSSION: These findings consolidated the close relationship between sleep and AD.

Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

Effects of propofol on sleep architecture and sleep-wake systems in rats.

Previous studies have shown that the synchronization of electroencephalogram (EEG) signals is found during propofol-induced general anesthesia, which is similar to that of slow-wave sleep (SWS). However, a complete understanding is lacking in terms of the characteristics of EEG changes in rats after propofol administration and whether propofol acts through natural sleep circuits. Here, we examined the characteristics of EEG patterns induced by intraperitoneal injection of propofol in rats. We found that high (10 mg/kg) and medium (5 mg/kg) doses of propofol induced a cortical EEG of low-frequency, high-amplitude activity with rare electromyographic activity and markedly shortened sleep latency. The high dose of propofol increased deep slow-wave sleep (SWS2) to 4 h, as well as the number of large SWS2 bouts (>480 s), their mean duration and the peak of the power density curve in the delta range of 0.75-3.25 Hz. After the medium dose of propofol, the total number of wakefulness, light slow-wave sleep (SWS1) and SWS2 episodes increased, whereas the mean duration of wakefulness decreased. The high dose of propofol significantly increased c-fos expression in the ventrolateral preoptic nucleus (VLPO) sleep center and decreased the number of c-fos-immunoreactive neurons in wake-related systems including the tuberomammillary nucleus (TMN), perifornical nucleus (PeF), lateral hypothalamic nucleus (LH), ventrolateral periaqueductal gray (vPAG) and supramammillary region (SuM). These results indicated that the high dose of propofol produced high-quality sleep by increasing SWS2, whereas the medium dose produced fragmented and low-quality sleep by disrupting the continuity of wakefulness. Furthermore, sleep-promoting effects of propofol are correlated with activation of the VLPO cluster and inhibition of the TMN, PeF, LH, vPAG and SuM.

NLRP3 inflammasome activation mediates sleep deprivation-induced pyroptosis in mice.

BACKGROUND: Sleep deprivation (SD) has many deleterious health effects, including cognitive decline, work ability decline, inadequate alertness, etc. Neuroinflammation plays an important role in sleep deprivation. However, the underlying mechanism is still unclear. METHODS: In the present study, we detected the activation of microglia and apoptosis of nerve cells in sleep deprivation (SD) mice model using IHC, HE staining and TUNEL apoptosis assay. RT-PCR array data were used to detect the expression of inflammatory bodies in hippocampal CA1 region after sleep deprivation, to explore how NLRP3 inflammasome regulates neuronal apoptosis and how specific signaling pathways are involved in SD-induced activation of NLRP3/pyrosis axis. RESULTS: We found the number of microglia significantly increased in SD mice, while this effect was blocked by sleep recovery. RT-PCR array data suggested that NLRP3 inflammasome, but not other inflammasomes, was obviously increased in hippocampus CA1 region after sleep deprivation. Mechanistically, we found that NLRP3 mediated the pyroptosis of neurocyte through GSDMD-dependent way , and P38 and ERK-MAPK signaling pathway is involved in SD-induced activation of NLRP3/pyroptosis axis. All these results suggested that MAPK/NLRP3 axis mediated SD-induced pyroptosis. CONCLUSION: NLRP3 plays an important role in SD-induced neuroinflammation. Thus, NLRP3 inflammasome is expected to be a potential therapeutic target for SD-induced neuroinflammation.

Morphine inhibits sleep-promoting neurons in the ventrolateral preoptic area via mu receptors and induces wakefulness in rats.

Morphine is the most efficacious and widely prescribed treatment for pain. However, it decreases the total amount of deep sleep and rapid eye movement sleep in humans. Acute morphine administration at low doses causes wakefulness in animal models. To clarify the mechanism by which morphine affects sleep-wake behavior, we investigated the effects of morphine on the sleep-promoting neurons of the ventrolateral preoptic area (VLPO), a putative sleep-active nucleus, using in vitro brain slices by the patch-clamp technique. We also examined the effects of morphine on sleep-wake profiles after administration of opioid receptor antagonist to the VLPO using EEG and electromyogram recordings in freely moving rats. The results showed that morphine inhibited the firing rate of sleep-promoting neurons and hyperpolarized their membrane potentials without affecting interneurons in the VLPO. Morphine-induced hyperpolarization of membrane potentials could be reversed by, D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a mu receptor antagonist, in the presence of tetrodotoxin. However, after the mu receptors were blocked by CTOP, morphine still suppressed the firing of the sleep-promoting neurons. This effect was antagonized by nor-BIN, a kappa receptor antagonist. Activation of kappa receptor by U50488H inhibited the firing of the sleep-promoting neurons. These results indicate that morphine could inhibit the activity of sleep-promoting neurons in the VLPO through mu and kappa receptors. EEG recordings revealed that morphine injected subcutaneously induced arousal in a dose-dependent manner. CTOP microinjected into VLPO antagonized the arousal effects of morphine, but nor-BIN did not. However, CTOP alone was not associated with any changes in the physiological sleep-wake cycle. Taken together, these findings clearly indicate that morphine inhibits sleep-promoting neurons in the VLPO by affecting mu receptors and so induces wakefulness in rats.

Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice.

BACKGROUND AND PURPOSE: Decoctions of the Chinese herb houpu contain honokiol and are used to treat a variety of mental disorders, including depression. Depression commonly presents alongside sleep disorders and sleep disturbances, which appear to be a major risk factor for depression. Here, we have evaluated the somnogenic effect of honokiol and the mechanisms involved. EXPERIMENTAL APPROACH: Honokiol was administered i.p. at 20:00 h in mice. Flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor, was administered i.p. 15 min before honokiol. The effects of honokiol were measured by EEG and electromyogram (EMG), c-Fos expression and in vitro electrophysiology. KEY RESULTS: Honokiol (10 and 20 mg·kg⁻¹) significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep and increased the amount of NREM sleep. Honokiol increased the number of state transitions from wakefulness to NREM sleep and, subsequently, from NREM sleep to wakefulness. However, honokiol had no effect on either the amount of REM sleep or EEG power density of both NREM and REM sleep. Honokiol increased c-Fos expression in ventrolateral preoptic area (VLPO) neurons, as examined by immunostaining, and excited sleep-promoting neurons in the VLPO by whole-cell patch clamping in the brain slice. Pretreatment with flumazenil abolished the somnogenic effects and activation of the VLPO neurons by honokiol. CONCLUSION AND IMPLICATIONS: Honokiol promoted NREM sleep by modulating the benzodiazepine site of the GABA(A) receptor, suggesting potential applications in the treatment of insomnia, especially for patients who experience difficulty in falling and staying asleep.