Activation of multiple neuromodulatory systems in alert rats acquiring conditioned taste aversion revealed by positron emission tomography.

Conditioned taste aversion (CTA) is an essential ability for animals to consume food safely and is regulated by neuromodulatory systems including the dopamine, noradrenaline, serotonin, and acetylcholine systems. However, because few studies focused on a comprehensive understanding of whole-brain activities, how these neuromodulators contribute to the process of CTA remains an open issue. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can visualize activated regions within the whole brain simultaneously and noninvasively. This study aimed to understand the mechanisms of CTA, especially focusing on the retrieval process after CTA acquisition by FDG-PET imaging. CTA was established in rats who received an intraoral application of saccharin solution (IOAS) on the first day (Day 1), a LiCl i.p. injection after an IOAS on Day 2, and an IOAS on Day 3 (CTA group). The subtraction images of Day 3 of the SHAM group, which received a 0.9 % NaCl (saline) injection instead of a LiCl on Day 2, from those of Day 3 of the CTA group revealed increases in FDG signals in multiple brain regions including the substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and nucleus basalis magnocellularis, in addition to the hippocampus and nociception-related regions, including the parabrachial nucleus and solitary nucleus. On the other hand, the visceral pain induced by the LiCl injection increased FDG signals in the primary and secondary somatosensory and insular cortices in addition to the parabrachial nucleus and solitary nucleus. These results suggest that the retrieval process of CTA induces brain regions producing neuromodulators and pain-related brainstem.

Sedation outcomes for remimazolam, a new benzodiazepine.

Remimazolam is a new ultrashort-acting benzodiazepine with fast onset, quick recovery, and few side effects, such as hypotension and respiratory depression. It is expected to be safe and effective for a wide range of patients undergoing intravenous sedation for dental procedures. The aim of this literature review was to evaluate clinical and sedation outcomes for remimazolam, including method of administration, level of sedation at the dose required, and clinical adverse events. An electronic literature search of databases was conducted, and eight articles were selected for inclusion in this review. Onset time from drug administration to optimal sedation level was faster for remimazolam (around 1.5-6.4 min) than for midazolam. Recovery time was significantly shorter for remimazolam than for midazolam and propofol. A study comparing various doses of remimazolam with midazolam found no significant difference in safety. Comparison of a remimazolam group with a propofol group showed that incidences of hypotension (13.0% vs 42.9%, respectively) and respiratory depression (1.1% vs 6.9%, respectively) were significantly lower for remimazolam. Remimazolam appears to be an ideal sedative.

Propofol decreases spike firing frequency with an increase in spike synchronization in the cerebral cortex.

Little is known about how propofol modulates the spike firing correlation between excitatory and inhibitory cortical neurons in vivo. We performed extracellular unit recordings from rat insular cortical neurons, and classified neurons with high spontaneous firing frequency, bursting, and short spike width as high frequency with bursting neurons (HFB; pseudo fast-spiking GABAergic neurons) and other neurons with low spontaneous firing frequency and no bursting were classified as non-HFB. Intravenous administration of propofol (12 mg/kg) from the caudal vein reduced the firing frequency of HFB, whereas propofol initially increased (within 30 s) and then decreased the firing frequency of non-HFB. Both HFB and non-HFB spontaneous action potential discharge was depressed by propofol with a greater depression seen for HFB. Cross-correlograms and auto-correlograms demonstrated propofol-induced increases in the ratio of the peak, which were mostly observed around 0-10 ms divided to baseline amplitude. The analysis of interspike intervals showed a decrease in spike firing at 20-100 Hz and a relative increase at 8-15 Hz. These results suggest that propofol induces a larger suppression of firing frequency in HFB and an enhancement of synchronized neural activities in the α frequency band in the cerebral cortex (192 words).

[Retrospective Examination of Usefulness and Adverse Effects of Tapentadol in Patients with Cancer Pain during Anticancer Treatment].

We retrospectively examined 106 cases of tapentadol use in Japan in August 2014 for cancer pain at our hospital.The advantage of the opioid medication tapentadol is that its introduction is suitable in patients undergoing anti-cancer treatment because of the low incidence of gastrointestinal symptoms, with glucuronidation involved in the metabolism, and lack of interactions with other drugs.However, depending on the dosage form and presence of swallowing disorders, the administration should be considered carefully.

[A New Twist on the Administration of Naldemedine for Opioid-Induced Constipation in an Outpatient].

Opioid-induced constipation(OIC)occurs with high frequency in patients with cancer undergoing pain treatment using opioids. Osmotic or irritant laxatives are usually used to prevent OIC. Recently, naldemedine has become operational for OIC. Although naldemedine achieved the desired effect, diarrhea is a little feared from the results of clinical phase III study(V9236 clinical trial). We herein report the use of naldemedine to alleviate diarrhea and expect the improvement of the quality of the bowel habits in outpatients with cancer undergoing pain treatment using opioids.

[Combinatorial Use of Rapid-Onset Opioid and Short-Acting Opioid Is Effective against Breakthrough Cancer Pain].

Breakthrough cancer pain is divided into "predictable breakthrough pain" and "unpredictable breakthrough pain". Uncontrolled breakthrough pain in cancer negatively affects the quality of life of the patients. The short-acting opioid(SAO) requires considerable time to produce analgesia, and is not adequate as a rescue drug. The rapid-onset opioid(ROO)immediately produces analgesia, but its appropriate usage is difficult. For instance, the frequency and interval of ROO usage is limited, making the optimization of dosage cumbersome. Therefore, ROO has not yet gained popularity. Here, we report that a combinatorial use of ROO and SAO is effective against breakthrough cancer pain, with SAO and ROO being suitable for "predictable breakthrough pain", and "unpredictable breakthrough pain", respectively. The effectiveness and safety of this combination were assessed for many patients with breakthrough cancer pain.