60 research outputs found

    Mas-related G-protein–coupled receptors inhibit pathological pain in mice

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    An important objective of pain research is to identify novel drug targets for the treatment of pathological persistent pain states, such as inflammatory and neuropathic pain. Mas-related G-protein–coupled receptors (Mrgprs) represent a large family of orphan receptors specifically expressed in small-diameter nociceptive primary sensory neurons. To determine the roles of Mrgprs in persistent pathological pain states, we exploited a mouse line in which a chromosomal locus spanning 12 Mrgpr genes was deleted (KO). Initial studies indicated that these KO mice show prolonged mechanical- and thermal-pain hypersensitivity after hind-paw inflammation compared with wild-type littermates. Here, we show that this mutation also enhances the windup response of dorsal-horn wide dynamic-range neurons, an electrophysiological model for the triggering of central pain sensitization. Deletion of the Mrgpr cluster also blocked the analgesic effect of intrathecally applied bovine adrenal medulla peptide 8–22 (BAM 8–22), an MrgprC11 agonist, on both inflammatory heat hyperalgesia and neuropathic mechanical allodynia. Spinal application of bovine adrenal medulla peptide 8–22 also significantly attenuated windup in wild-type mice, an effect eliminated in KO mice. These data suggest that members of the Mrgpr family, in particular MrgprC11, may constitute an endogenous inhibitory mechanism for regulating persistent pain in mice. Agonists for these receptors may, therefore, represent a class of antihyperalgesics for treating persistent pain with minimal side effects because of the highly specific expression of their targets

    Conservation of core complex subunits shaped the structure and function of photosystem I in the secondary endosymbiont alga Nannochloropsis gaditana

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    Photosystem I (PSI) is a pigment protein complex catalyzing the light-driven electron transport from plastocyanin to ferredoxin in oxygenic photosynthetic organisms. Several PSI subunits are highly conserved in cyanobacteria, algae and plants, whereas others are distributed differentially in the various organisms. Here we characterized the structural and functional properties of PSI purified from the heterokont alga Nannochloropsis gaditana, showing that it is organized as a supercomplex including a core complex and an outer antenna, as in plants and other eukaryotic algae. Differently from all known organisms, the N. gaditana PSI supercomplex contains five peripheral antenna proteins, identified by proteome analysis as type-R light-harvesting complexes (LHCr4-8). Two antenna subunits are bound in a conserved position, as in PSI in plants, whereas three additional antennae are associated with the core on the other side. This peculiar antenna association correlates with the presence of PsaF/J and the absence of PsaH, G and K in the N. gaditana genome and proteome. Excitation energy transfer in the supercomplex is highly efficient, leading to a very high trapping efficiency as observed in all other PSI eukaryotes, showing that although the supramolecular organization of PSI changed during evolution, fundamental functional properties such as trapping efficiency were maintained

    Genetic Evidence for Involvement of Neuronally Expressed S1P1 Receptor in Nociceptor Sensitization and Inflammatory Pain

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    Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P1 receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P1 receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P1 receptor. Our data show that neuronally expressed S1P1 receptors play a significant role in regulating nociceptor function and that S1P/S1P1 signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation

    Demographic outlook in the European Union 2017

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    This paper presents the demographic outlook in the European Union (EU) in 2017. It shows that the EU population, having grown substantially, is now beginning to stagnate, before its expected decline from around the middle of the century. With the world population having risen still more substantially and growth continuing, the EU represents a shrinking proportion of the world population. The EU population is also ageing dramatically, as life expectancy increases and fertility rates are lower than in the past. This has serious implications across a range of areas including the economy, healthcare and pensions. Free movement within the EU and migration from third countries also plays an important role in shaping demography in individual Member States and regions. The 'in-focus' section of this analysis looks at health and notes that the data, whilst inconsistent, suggests that people are not necessarily experiencing the extra life years without limitations to their usual activity

    Compendium of dyadic intervention techniques (DITs) to change health behaviours: a systematic review.

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    BACKGROUND Dyadic interventions for health behaviour change involving the romantic partner are promising. However, it often remains unclear how exactly the partner is involved in dyadic interventions. We propose a novel compendium of dyadic intervention techniques (DITs) that facilitates systematic description of dyadic interventions in terms of who performs what for whom during intervention delivery and subsequent implementation. OBJECTIVE We aimed to systematically characterise dyadic interventions along their degree of partner involvement and to provide a comprehensive list of DITs used in dyadic interventions with romantic partners. METHODS We systematically reviewed dyadic health behaviour change interventions with controlled designs. We included 165 studies describing 122 distinct dyadic interventions with romantic partners. Interventions were classified along their degree of partner involvement, 160 DITs were extracted, and their frequencies of use counted. RESULTS The majority of interventions (n = 90, 74%) explicitly instructed partners to interact. Half of the DITs were performed jointly by the couple and also targeted the couple. Mostly, couples were instructed to jointly practice communication skills and to jointly perform problem solving for the couple. DISCUSSION The present review contributes to the development of a shared and systematic way of describing dyadic interventions to facilitate cumulation of evidence
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