Search

The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain-induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)-projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain-induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.

The authors conducted droplet evaporation experiments of light cycle oil (LCO) at various ambient temperatures and pressures. Five kinds of LCO and three kinds of arranged fuels were used. We investigated the evaporation characteristics of LCO and the relationships between the evaporation characteristics and the cetane index. In addition to that, a surrogate fuel composed of four chemical species, which can simulate the droplet evaporation characteristics of LCO, was suggested. Experimental results show that the differences in droplet lifetime between fuel species become larger with decreasing ambient temperature. This is because the low volatile component made the evaporation rate outstandingly slow at a low ambient temperature. It was found that the relationship between droplet lifetime and the late-stage distillation temperature becomes stronger at low ambient temperature and high ambient pressure. By an analysis employing the properties of chemical species in LCO surrogate fuel, it is clarified that the mass evaporation rate becomes smaller than the internal diffusion, which is the condition similar to that in the distillation test. Finally, the relationship between the droplet lifetime and the cetane index was investigated. It can be concluded that the droplet lifetime is independent of the cetane index under all conditions tested in this study. The experimental data obtained by this research can be utilized for the validation of multicomponent fuel droplet evaporation models in the future.

Although dysfunction of the mesolimbic dopaminergic system has been implicated in chronic pain, the underlying mechanisms remain to be elucidated. We hypothesized that increased inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dIBNST) to the ventral tegmental area (VTA) during chronic pain may induce tonic suppression of the mesolimbic dopaminergic system. To test this hypothesis, male Sprague Dawley rats were subjected to spinal nerve ligation to induce neuropathic pain and then spontaneous IPSCs (sIPSCs) were measured in this neuronal pathway. Whole-cell patch-clamp electrophysiology of brain slices containing the dlBNST revealed that the frequency of sIPSCs significantly increased in VTA-projecting dlBNST neurons 4 weeks after surgery. Next, the role of corticotropin-releasing factor (CRF) signaling within the dlBNST in the increased sIPSCs was examined. CRF increased the frequency of sIPSCs in VTA-projecting dlBNST neurons in sham-operated controls, but not in chronic pain rats. By contrast, NBI27914, a CRF type 1 receptor antagonist, decreased the frequency of sIPSCs in VTA-projecting dlBNST neurons in the chronic pain rats, but not in the control animals. In addition, histological analyses revealed the increased expression of CRF mRNA in the dlBNST. Finally, bilateral injections of NBI27914 into the dlBNST of chronic pain rats activated mesolimbic dopaminergic neurons and induced conditioned place preference. Together, these results suggest that the mesolimbic dopaminergic system is tonically suppressed during chronic pain by enhanced CRF signaling within the dlBNST via increased inhibitory inputs to VTA-projecting dlBNST neurons.

BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H-3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H-3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H-3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H-2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H-3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrains.

BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H-3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H-3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H-3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H-2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H-3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrains.

会議情報: 第32回宇宙環境利用シンポジウム (2018年1月15日-16日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Meeting Information: Space Utilization Research (January 15-16, 2018. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan

会議情報: 第31回宇宙環境利用シンポジウム (2017年1月16日-17日. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS)), 相模原市, 神奈川県, Meeting Information: Space Utilization Research (January 16-17, 2017. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS)), Sagamihara, Kanagawa Japan

type:text, Two-sensor method proposed by Fusco et al. [“Two-sensor power measurements in lossy ducts,” J. Acoust. Soc. Am. 91, 2229-2235 (1992)] is a novel technique that determines acoustic intensity of a gas column in a wide duct from measurements of pressure based on the boundary layer approximation. For further development of this method, its validity is experimentally tested through comparison with the direct method measuring the pressure and the velocity simultaneously, and its formulation is modified to include the narrow duct range where the duct radius is smaller than the viscous boundary layer thickness of the gas. It is shown that the modified two-sensor method enables quick and accurate evaluation of the acoustic intensity seamlessly from narrow to wide duct ranges.