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Purpose The aim of this study was to investigate the effects of end-tidal carbon dioxide tension (ETCO.sub.2) changes during remifentanil infusion on mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue oxygen tension (PbO.sub.2) and masseter muscle tissue oxygen tension (PmO.sub.2) in rabbits. Methods Ten male tracheotomized Japan White rabbits were anesthetized and ventilated with sevoflurane. ETCO.sub.2 was adjusted to 30 mmHg. After baseline measurement, CO.sub.2 was added to the inhaled air, and ETCO.sub.2 was increased to 40 and 60 mmHg. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), BBF, MBF, PbO.sub.2, and PmO.sub.2 were recorded with and without remifentanil infusion at 0.4 [micro]g/kg/min. Results Two-way repeated measures analysis of variance showed no interaction between ETCO.sub.2 and remifentanil in all variables. Remifentanil infusion produced decreases in HR, SBP, MAP, BBF and MBF compared with those without remifentanil infusion, while it did not affect DBP, PbO.sub.2 and PmO.sub.2. Elevation of ETCO.sub.2 from 30 to 60 mmHg produced decreases in HR and MBF, and increases in SBP, DBP, MAP and BBF, while it did not affect PbO.sub.2 and PmO.sub.2. Conclusion PbO.sub.2 and PmO.sub.2 remained unchanged despite changes in BBF and MBF during ETCO.sub.2 change with or without remifentanil infusion., Author(s): Ai Yamazaki [sup.1], Masataka Kasahara [sup.2], Kyotaro Koshika [sup.1], Yui Akiike [sup.1], Nobuyuki Matsuura [sup.3], Tatsuya Ichinohe [sup.1] Author Affiliations: (1) grid.265070.6, 0000 0001 1092 3624, Department of Dental [...]

Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the TMEM132C rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, p = 0.0001; CIH group, p = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the TMEM132C rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use. [ABSTRACT FROM AUTHOR]

Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 (PAR2/F2RL1) and interleukin 17A (IL-17A/IL17A) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case–control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine. [ABSTRACT FROM AUTHOR]

Purpose To determine whether continuous administration of nitrous oxide and remifentanil-either alone or together-alters blood flow in oral tissues during sevoflurane anesthesia. Methods Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 [mu]g/kg/min remifentanil, and their combination) for 20 min. Results Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Conclusions Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits., Author(s): Masataka Kasahara[sup.1] , Tatsuya Ichinohe[sup.2] , Sota Okamoto[sup.2] , Reina Okada[sup.2] , Hiroaki Kanbe[sup.2] , Nobuyuki Matsuura[sup.2] Author Affiliations: (1) Department of Pharmacology, Tokyo Dental College, Misaki-cho 2-1-14, Chiyoda-ku, [...]

An inflammatory response following dental pulp injury and/or infection often leads to neurogenic inflammation via the axon reflex. However, the detailed mechanism underlying the occurrence of the axon reflex in the dental pulp remains unclear. We sought to examine the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway in odontoblasts via the activation of Gs protein-coupled receptors and intercellular trigeminal ganglion (TG) neuron–odontoblast communication following direct mechanical stimulation of TG neurons. Odontoblasts express heterotrimeric G-protein α-subunit Gαs and calcitonin receptor-like receptors. The application of an adenylyl cyclase (AC) activator and a calcitonin gene-related peptide (CGRP) receptor agonist increased the intracellular cAMP levels ([cAMP]i) in odontoblasts, which were significantly inhibited by the selective CGRP receptor antagonist and AC inhibitor. Mechanical stimulation of the small-sized CGRP-positive but neurofilament heavy chain-negative TG neurons increased [cAMP]i in odontoblasts localized near the stimulated neuron. This increase was inhibited by the CGRP receptor antagonist. In the mineralization assay, CGRP impaired the mineralization ability of the odontoblasts, which was reversed by treatment with a CGRP receptor antagonist and AC inhibitor. CGRP establishes an axon reflex in the dental pulp via intercellular communication between TG neurons and odontoblasts. Overall, CGRP and cAMP signaling negatively regulate dentinogenesis as defensive mechanisms. [ABSTRACT FROM AUTHOR]

Bradykinin (BK) and its receptors, B.sub.1 and B.sub.2, in trigeminal ganglion (TG) neurons are involved in the regulation of pain. Recent studies have revealed that B.sub.1 receptors are expressed in neonatal rat TG neurons; however, the intracellular signaling pathway following B.sub.1 receptor activation remains to be elucidated. To investigate the mechanism by which B.sub.1 receptor activation leads to intracellular Ca.sup.2+ mobilization, we measured the intracellular free Ca.sup.2+ concentration ([Ca.sup.2+].sub.i) in primary-cultured TG neurons. The application of Lys-[Des-Arg.sup.9]BK (B.sub.1 receptor agonist) increased the [Ca.sup.2+].sub.i in these TG neurons even in the absence of extracellular Ca.sup.2+. Pretreatment with inhibitors of ryanodine receptors or sarco/endoplasmic reticulum Ca.sup.2+-ATPase suppressed the increase in Lys-[Des-Arg.sup.9]BK-induced [Ca.sup.2+].sub.i. The Lys-[Des-Arg.sup.9]BK-induced [Ca.sup.2+].sub.i increase was unaffected by phospholipase-C inhibitor. B.sub.1 receptor activation-induced [Ca.sup.2+].sub.i increase was suppressed by phosphodiesterase inhibitor and enhanced by adenylyl cyclase inhibitor. These results suggest that B.sub.1 receptor activation suppresses intracellular cAMP production via adenylyl cyclase inhibition and mobilizes intracellular Ca.sup.2+ via ryanodine receptors that access intracellular Ca.sup.2+ stores. Keywords: Adenylyl cyclase, Ca.sup.2+ mobilization, Cyclic AMP, G protein, Ryanodine receptors, Trigeminal ganglion neuron, Author(s): Reiko Terashima[sup.1,2], Maki Kimura[sup.2], Asuka Higashikawa[sup.2], Yuki Kojima[sup.2], Tatsuya Ichinohe[sup.1], Masakazu Tazaki[sup.2] and Yoshiyuki Shibukawa[sup.2] Introduction Bradykinin (BK) and related peptides play important roles in the modulation of physiological [...]