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Chronic pain often has an unknown cause, and many patients with chronic pain learn to accept that their pain is incurable and pharmacologic treatments are only temporarily effective. Complementary and integrative health approaches for pain are thus in high demand. One such approach is soft touch, e.g., adhesion of pyramidal thorn patches in a pain region. The effects of patch adhesion on pain relief have been confirmed in patients with various types of pain. A recent study using near-infrared spectroscopy revealed that the dorsolateral prefrontal cortex (DLPFC), especially the left side, is likely to be inactivated in patients experiencing pain relief during patch treatment. Mindfulness meditation is another well-known complementary and integrative approach for achieving pain relief. The relation between pain relief due to mindfulness meditation and changes in brain regions, including the DLPFC, has long been examined. In the present review article, we survey the literature describing the effects of the above-mentioned complementary and integrative treatments on pain relief, and outline the important brain regions, including the DLPFC, that are involved in analgesia. We hope that the present article will provide clues to researchers who hope to advance neurosensory treatments for pain relief without medication. [ABSTRACT FROM AUTHOR]

Stimulus-specific adaptation (SSA) is considered to be the neural underpinning of habituation to frequent stimuli and novelty detection. However, neither the cellular mechanism underlying SSA nor the link between SSA-like neuronal plasticity and behavioral modulation is well understood. The wind-detection system in crickets is one of the best models for investigating the neural basis of SSA. We found that crickets exhibit stimulus-direction-specific adaptation in wind-elicited avoidance behavior. Repetitive air currents inducing this behavioral adaptation reduced firings to the stimulus and the amplitude of excitatory synaptic potentials in wind-sensitive giant interneurons (GIs) related to the avoidance behavior. Injection of a Ca2+ chelator into GIs diminished both the attenuation of firings and the synaptic depression induced by the repetitive stimulation, suggesting that adaptation of GIs induced by this stimulation results in Ca2+-mediated modulation of postsynaptic responses, including postsynaptic short-term depression. Some types of GIs showed specific adaptation to the direction of repetitive stimuli, resulting in an alteration of their directional tuning curves. The types of GIs for which directional tuning was altered displayed heterogeneous direction selectivity in their Ca2+ dynamics that was restricted to a specific area of dendrites. In contrast, other types of GIs with constant directionality exhibited direction-independent global Ca2+elevation throughout the dendritic arbor. These results suggest that depression induced by local Ca2+ accumulation at repetitively activated synapses of key neurons underlies direction-specific behavioral adaptation. This input-selective depression mediated by heterogeneous Ca2+ dynamics could confer the ability to detect novelty at the earliest stages of sensory processing in crickets. [ABSTRACT FROM AUTHOR]

Some evidence suggests that oxytocin, which is a neuropeptide conventionally thought to be synthesized in the hypothalamus and released by the posterior pituitary, is generated in peripheral keratinocytes, but the details are lacking and the mRNA analysis is further required. Oxytocin and neurophysin I are generated together as cleavage products after splitting the precursor molecule, preprooxyphysin. To confirm that oxytocin and neurophysin I are also generated in the peripheral keratinocytes, it must first be clarified that these molecules contained in peripheral keratinocytes did not originate in the posterior pituitary gland and then the expression of oxytocin and neurophysin I mRNAs must be established in keratinocytes. Therefore, we attempted to quantify preprooxyphysin mRNA in keratinocytes using various primers. Using real-time PCR, we observed that the mRNAs of both oxytocin and neurophysin I were located in keratinocytes. However, the mRNA amounts of oxytocin, neurophysin I, and preprooxyphysin were too small to confirm their co-existence in keratinocytes. Thus, we had to further determine whether the PCR-amplified sequence was identical to preprooxyphysin. The PCR products analyzed by DNA sequencing were identical to preprooxyphysin, finally determining the co-existence of both oxytocin and neurophysin I mRNAs in keratinocytes. In addition, the immunocytochemical experiments showed that oxytocin and neurophysin I proteins were located in keratinocytes. These results of the present study provided further support indicating that oxytocin and neurophysin I are generated in peripheral keratinocytes. [ABSTRACT FROM AUTHOR]

pH-responsive spirocyclic cyanine dyes were designed and synthesized. The equilibrium constant for cyclization (pKcycl) could be rationally controlled by changing the nucleophilic moiety and the side chains. Encapsulation in polymeric micelles inhibited the H-aggregation of the dye, and the pKcycl could be shifted according to the amphiphilic polymer employed. [ABSTRACT FROM AUTHOR]

Epidermal cells, such as keratinocytes, are regarded as the first sensory cells to transmit nociception and mechanoreception to free nerve endings extended from the dorsal root ganglion (DRG). Previous studies suggested that this transmission occurs as Ca2+ propagation via ATP receptors. Conversely, the influence of gap junctions on this Ca2+ propagation is largely unknown. Thus, we examined the localization and the role of connexin 43 among keratinocytes and DRG neurons. We co-cultured keratinocytes and DRG neurons and investigated the effect of pharmacological blockade of gap junctions on Ca2+ propagation upon stimulation of a single keratinocyte. Immunocytochemical experiments showed that connexin 43 is localized between keratinocytes and between keratinocytes and DRG neurons. Octanol, a gap junction inhibitor, significantly suppressed the concentrical Ca2+ propagation. Therefore, we conclude that the Ca2+ propagation mechanism via gap junctions from stimulated keratinocytes to free nerve endings should be taken into account. [ABSTRACT FROM AUTHOR]

As human-origin cells, human dental pulp stem cells (hDPSCs) are thought to be potentially useful for biological and medical experiments. They are easily obtained from lost primary teeth or extracted wisdom teeth, and they are mesenchymal stem cells that are known to differentiate into osteoblasts, chondrocytes, and adipocytes. Although hDPSCs originate from neural crest cells, it is difficult to induce hDPSCs to differentiate into neuron-like cells. To facilitate their differentiation into neuron-like cells, we evaluated various differentiation conditions. Activation of K+ channels is thought to regulate the intracellular Ca2+ concentration, allowing for manipulation of the cell cycle to induce the differentiation of hDPSCs. Therefore, in addition to a conventional neural cell differentiation protocol, we activated K+ channels in hDPSCs. Immunocytochemistry and real-time PCR revealed that applying a combination of 3 stimuli (high K+ solution, epigenetic reprogramming solution, and neural differentiation solution) to hDPSCs increased their expression of neuronal markers, such as ß3-tubulin, postsynaptic density protein 95, and nestin within 5 days, which led to their rapid differentiation into neuron-like cells. Our findings indicate that epigenetic reprogramming along with cell cycle regulation by stimulation with high K+ accelerated the differentiation of hDPSCs into neuronlike cells. Therefore, hDPSCs can be used in various ways as neuron-like cells by manipulating their cell cycle. [ABSTRACT FROM AUTHOR]

Exploring for food is important in food-deprived condition. Chemotaxis is one of the important behaviors to search food. Although chemotactic strategies in C. elegans have been well investigated: the pirouette and the weathervane strategies, the change of the chemotactic strategy by food deprivation is largely unclear. Here, we show the change of chemotactic strategy by food deprivation, especially for isoamyl alcohol. To compare chemotaxis under different food-deprivation period, we showed that worms change their chemotactic behaviors by food deprivation. The worms with 1-h food-deprivation change the weathervane strategy. On the other hand, 6-h food deprived animals change the pirouette strategy. These results demonstrate that worms change chemotactic strategy different way depend on period of food deprivation. [ABSTRACT FROM AUTHOR]

The Ciona notochord has emerged as a simple and tractable in vivo model for tubulogenesis. Here, using a chemical genetics approach, we identified UTKO1 as a selective small molecule inhibitor of notochord tubulogenesis. We identified 14-3-3ea protein as a direct binding partner of UTKO1 and showed that 14-3-3ea knockdown leads to failure of notochord tubulogenesis. We found that UTKO1 prevents 14-3-3ea from interacting with ezrin/radixin/ moesin (ERM), which is required for notochord tubulogenesis, suggesting that interactions between 14-3-3ea and ERM play a key role in regulating the early steps of tubulogenesis. Using live imaging, we found that, as lumens begin to open between neighboring cells, 14-3-3ea and ERM are highly colocalized at the basal cortex where they undergo cycles of accumulation and disappearance. Interestingly, the disappearance of 14-3-3ea and ERM during each cycle is tightly correlated with a transient flow of 14-3-3ea, ERM, myosin II, and other cytoplasmic elements from the basal surface toward the lumen-facing apical domain, which is often accompanied by visible changes in lumen architecture. Both pulsatile flow and lumen formation are abolished in larvae treated with UTKO1, in larvae depleted of either 14-3-3ea or ERM, or in larvae expressing a truncated form of 14-3-3ea that lacks the ability to interact with ERM. These results suggest that 14-3-3ea and ERM interact at the basal cortex to direct pulsatile basal accumulation and basal-apical transport of factors that are essential for lumen formation. We propose that similar mechanisms may underlie or may contribute to lumen formation in tubulogenesis in other systems. [ABSTRACT FROM AUTHOR]

In many species, individual social animals interact with others in their group and change their collective behaviours. For the solitary nematode Caenorhabditis elegans strain N2, previous research suggests that individuals can change the behaviour of other worms via pheromones and mechanosensory interactions. In particular, pheromones affect foraging behaviour, so that the chemotactic behaviours of individuals in a group (population) can be modulated by interactions with other individuals in the population. To investigate this, we directly compared the chemotactic behaviours of isolated (single) worms with those of individual animals within a population. We found that worms approached an odour source in a distinct manner depending on whether they were alone or in a population. Analysis of behaviours of the N2 worm and a pheromone productiondefective mutant revealed that the 'pirouette' strategy was modulated by interaction of the worms via pheromones. Thus, pheromones play an important role in the characteristic collective behaviours seen in the population condition. [ABSTRACT FROM AUTHOR]

A purpose-designed porphyrin--peptide hybrid effectively degraded amyloid β monomer and oligomers associated with Alzheimer's disease. Degradation was achieved using light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrid effectively neutralized the cytotoxicity of amyloid β in PC12 cells upon photoirradiation. [ABSTRACT FROM AUTHOR]

Although the magnesium ion (Mg2+) is one of the most abundant divalent cations in cells and is known to play critical roles in many physiological processes, its mobilization and underlying mechanisms are still unknown. Here, we describe a novel fluorescent Mg2+ probe, "KMG-104-AsH", composed of a highly selective fluorescent Mg2+ probe, "KMG-104", and a fluorescence-recoverable probe, "FlAsH", bound specifically to a tetracysteine peptide tag (TCtag), which can be genetically incorporated into any protein. This probe was developed for molecular imaging of local changes in intracellular Mg2+ concentration. KMG-104-AsH was synthesized, and its optical properties were investigated in solution. The fluorescence intensity of KMG-104-AsH (at -λem/max = 540 nm) increases by more than 10-fold by binding to both the TCtag peptide and Mg2+, and the probe is highly selective for Mg2+ (Kd/Mg =1.7 mM, Kd/Ca ⪢ 100 mM). Application of the probe for imaging of Mg2+ in HeLa cells showed that this FlAsH-type Mg2+ sensing probe is membrane-permeable and binds specifically to tagged proteins, such as TCtag-actin and mKeima-TCtag targeted to the cytoplasm and the mitochondrial intermembrane space. KMG-104-AsH bound to TCtag responded to an increase in intracellular Mg2+ concentration caused by the release of Mg2+ from mitochondria induced by FCCP, a protonophore that eliminates the inner membrane potential of mitochondria. This probe is expected to be a strong tool for elucidating the dynamics and mechanisms of intracellular localization of Mg2+. [ABSTRACT FROM AUTHOR]

Axon guidance involves multiple second messenger signal transduction pathways. Although each signal transduction pathway has been characterized, only a few studies have examined crosstalk between these cascades. Here, we applied a simultaneous second messenger imaging method to the growth cone and demonstrated correlations between cAMP, cGMP, and Ca2+. The levels of cAMP and cGMP in non-stimulated freely extending growth cones showed a negative correlation without delay. Although there was no direct correlation between cAMP and Ca2+, examination of cross correlations using small time windows showed frequent switching behavior from negative to positive and vice versa. Furthermore, spatially asymmetric cAMP and cGMP signals in freely deviating growth cones were visualized directly. These results indicate that we succeed in relating second messenger crosstalk to growth cone deviation and extension, and also indicate the possibility of predicting axon guidance from this second messenger crosstalk. [ABSTRACT FROM AUTHOR]