BACKGROUND:Persistent pain after breast cancer surgery (PPBCS) affects 20-35% of patients, significantly impacting their quality of life. Although prevention through perioperative intervention is crucial, effective strategies to prevent PPBCS have not been established. In particular, the role of anesthetic management in preventing PPBCS remains controversial. METHODS:This multicenter, retrospective, observational study included 183 women aged 20-70 years who underwent unilateral breast cancer surgery under general anesthesia between April 2012 and March 2014. Pain was assessed using a numerical rating scale (NRS) during follow-up visits. PPBCS was categorized as 'no' (NRS = 0), 'mild' (NRS = 1-2), and 'moderate-to-severe' (NRS ≥ 3) pain. Univariate and multivariate analyses evaluated associations between perioperative factors and PPBCS. RESULTS:Of 183 participants, 127 (69.4%) reported PPBCS: 59 (32.2%) mild and 68 (37.2%) moderate-to-severe. No significant associations were found between anesthetic management factors (including total intravenous anesthesia vs. volatile anesthesia, intraoperative opioid doses, and use of adjuvant analgesics) and PPBCS incidence or intensity. Axillary lymph node dissection was significantly associated with moderate-to-severe PPBCS (odds ratio: 2.04; 95% confidence interval: 1.04-4.00). CONCLUSION:No significant associations were found between anesthetic management and PPBCS. Further research is needed to identify anesthetic factors that may prevent PPBCS.

[ 11 C]K-2, a radiotracer exhibiting high affinity and selectivity for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), is suitable for the quantification of AMPARs in living human brains and potentially useful in the identification of epileptogenic foci in patients. This study aimed to estimate the radiation doses of [ 11 C]K-2 in various organs and calculate the effective dose after injection of [ 11 C]K-2 in healthy human subjects. Twelve healthy male subjects were registered and divided into two groups (370 or 555 MBq of [ 11 C]K-2), followed by 2 h whole-body scans. We estimated the radiation dose of each organ and then calculated the effective dose for each subject. The highest uptake of [ 11 C]K-2 was observed in the liver, while the brain also showed relatively high uptake. The urinary bladder exhibited the highest radiation dose. The kidneys and liver also showed high radiation doses after [ 11 C]K-2 injections. The effective dose of [ 11 C]K-2 ranged from 5.0 to 5.2 μSv/MBq. Our findings suggest that [ 11 C]K-2 is safe in terms of the radiation dose and adverse effects. The injection of 370–555 MBq (10 to 15 mCi) for PET studies using this radiotracer is applicable in healthy human subjects and enables serial PET scans in a single subject.

In the central nervous system, glycine plays an excitatory role via binding to the NMDA receptors (NMDARs) and an inhibitory role via binding to the glycine receptors (GlyRs). Recently, it has been found that upon the increase of glycine concentration in the synaptic cleft, glycine binds to the GlyRs, mainly expressed in the extrasynapse, and introduces LTD. In addition, NMDARs and AMPA receptors (AMPARs) involve in this type of LTD. To elucidate the mechanisms underlying glycine-dependent LTD, we examined the phosphorylation of AMPARs under excess amount of glycine. Furthermore, we hypothesized that the administration of high-dose glycine would attenuate hippocampal- dependent fear memory, known to require the phosphorylation of AMPARs. We performed biochemical analysis to examine the phosphorylation status of AMPARs in the hippocampus under different doses of glycine. Glycine decreased the phosphorylation of serine 845 of GluA1 subunit of AMPARs dose-dependently. Furthermore, high-dose glycine co-incubated with strychnine, AP5 and FK506 did not show the reduction in the phosphorylation of serine 845 of GluA1, suggesting that this effect of glycine was mediated by not only GlyRs but also NMDARs. Interestingly, the high-dose administration of glycine to the rats before fear conditioning reduced the freezing behavior during the test. Moreover, this effect was eliminated by co-administration of strychnine. In this study, we revealed that LTD required the dephosphorylation of serine 845 of GluA1 and this type of LTD could attenuate contextual fear memory.

Background. We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods. One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US$0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results. In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion. In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.

Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depression test battery, sociability test battery, attention test battery, and learning test battery, which were started 7 days after anesthesia with 1.8% isoflurane. In addition to the control group, we included a yoked control group that was exposed to the same stress of handling as the isoflurane-treated animals before being anesthetized. Our comprehensive behavioral test batteries revealed impaired latent inhibition in the isoflurane-treated group, but the concentration of residual isoflurane in the brain was presumably negligible. The yoked control group and isoflurane-treated group exhibited higher anxiety in the elevated plus-maze test and impaired learning function in the cued fear conditioning test. No influences were observed in sensory functions, motor functions, antidepressant behaviors, and social behaviors. A number of papers have reported an effect of isoflurane on animal behaviors, but no systematic investigation has been performed. To the best of our knowledge, this study is the first to systematically investigate the general health, neurological reflexes, sensory functions, motor functions, and higher behavioral functions of mice exposed to isoflurane as adults. Our results suggest that the postanesthetic effect of isoflurane causes attention deficit in mice. Therefore, isoflurane must be used with great care in the clinical setting and veterinary anesthesia.

BackgroundThe descending antinociceptive system (DAS) is thought to play crucial roles in the antinociceptive effect of spinal cord stimulation (SCS), especially through its serotonergic pathway. The nucleus raphe magnus (NRM) in the rostral ventromedial medulla is a major source of serotonin [5-hydroxytryptamine (5-HT)] to the DAS, but the role of the dorsal raphe nucleus (DRN) in the ventral periaqueductal gray matter is still unclear. Moreover, the influence of the noradrenergic pathway is largely unknown. In this study, we evaluated the involvement of these serotonergic and noradrenergic pathways in SCS-induced antinociception by behavioral analysis of spinal nerve-ligated (SNL) rats. We also investigated immunohistochemical changes in the DRN and locus coeruleus (LC), regarded as the adrenergic center of the DAS, and expression changes of synthetic enzymes of 5-HT [tryptophan hydroxylase (TPH)] and norepinephrine [dopamine β-hydroxylase (DβH)] in the spinal dorsal horn. ResultsIntrathecally administered methysergide, a 5-HT1-and 5-HT2-receptor antagonist, and idazoxan, an α2-adrenergic receptor antagonist, equally abolished the antinociceptive effect of SCS. The numbers of TPH-positive serotonergic and phosphorylated cyclic AMP response element binding protein (pCREB)-positive neurons and percentage of pCREB-positive serotonergic neurons in the DRN significantly increased after 3-h SCS. Further, the ipsilateral-tocontralateral immunoreactivity ratio of DβH increased in the LC of SNL rats and reached the level seen in naïve rats, even though the number of pCREB-positive neurons in the LC was unchanged by SNL and SCS. Moreover, 3-h SCS did not increase the expression levels of TPH and DβH in the spinal dorsal horn. ConclusionsThe serotonergic and noradrenergic pathways of the DAS are involved in the antinociceptive effect of SCS, but activation of the DRN might primarily be responsible for this effect, and the LC may have a smaller contribution. SCS does not potentiate the synthetic enzymes of 5HT and norepinephrine in the neuropathic spinal cord.