Central nervous system mast cells in peripheral inflammatory nociception

<p>Abstract</p> <p>Background</p> <p>Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation.</p> <p>Results</p> <p>Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP) at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk) inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia.</p> <p>Conclusion</p> <p>The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.</p

Comparative chemistry of diffuse clouds III: sulfur-bearing molecules

Using data from IRAM's Plateau de Bure Interferometer and 30 m Telescope, we discuss the mm-wave absorption lines of CS, SO, H2S and HCS+ which arise in diffuse clouds occulting several extragalactic continuum sources. Typical relative abundances are X(CS)/X(HCO+) ~ 2, X(CS)/X(SO) ~ 2, X(CS)/X(H2S) ~ 6 and X(CS)/X(HCS+) ~ 13.Comment: Accepted by A&A 2002-Jan-1

Adaptive Movement Compensation for In Vivo Imaging of Fast Cellular Dynamics within a Moving Tissue

In vivo non-linear optical microscopy has been essential to advance our knowledge of how intact biological systems work. It has been particularly enabling to decipher fast spatiotemporal cellular dynamics in neural networks. The power of the technique stems from its optical sectioning capability that in turn also limits its application to essentially immobile tissue. Only tissue not affected by movement or in which movement can be physically constrained can be imaged fast enough to conduct functional studies at high temporal resolution. Here, we show dynamic two-photon Ca2+ imaging in the spinal cord of a living rat at millisecond time scale, free of motion artifacts using an optical stabilization system. We describe a fast, non-contact adaptive movement compensation approach, applicable to rough and weakly reflective surfaces, allowing real-time functional imaging from intrinsically moving tissue in live animals. The strategy involves enslaving the position of the microscope objective to that of the tissue surface in real-time through optical monitoring and a closed feedback loop. The performance of the system allows for efficient image locking even in conditions of random or irregular movements

A lambda = 1.3 mm and 2 mm molecular line survey towards M82

We study the chemical complexity towards the central parts of the starburst galaxy M82, and investigate the role of certain molecules as tracers of the physical processes in the galaxy circumnuclear region. We carried out a spectral line survey with the IRAM-30m telescope towards the northeastern molecular lobe of M82. It covers the frequency range between 129.8 GHz and 175.0 GHz in the 2 mm atmospheric window, and between 241.0 GHz and 260.0 GHz in the 1.3 mm atmospheric window. Sixty-nine spectral features corresponding to 18 different molecular species are identified. In addition, three hydrogen recombination lines are detected. The species NO, H2S, H2CS, NH2CN, and CH3CN are detected for the first time in this galaxy. Assuming local thermodynamic equilibrium, we determine the column densities of all the detected molecules. We also calculated upper limits to the column densities of fourteen other important, but undetected, molecules, such as SiO, HNCO, or OCS. We compare the chemical composition of the two starburst galaxies M82 and NGC253. This comparison enables us to establish the chemical differences between the products of the strong photon-dominated regions (PDRs) driving the heating in M82, and the large-scale shocks that influence the properties of the molecular clouds in the nucleus of NGC253. Overall, both sources have different chemical compositions. Some key molecules highlight the different physical processes dominating both central regions. Examples include CH3CCH, c-C3H2, or CO+, the abundances of which are clearly higher in M82 than in NGC253, pointing at photodissociating regions. On the other hand, species such as CH2NH, NS, SiO, and HOCO+ have abundances of up to one order of magnitude higher in NGC253 than in M82.Comment: Accepted for publication in A&A. 19 pages, 8 figures, 3 table

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents

Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide (10panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia

Temperature thresholds for chlorine activation and ozone loss in the polar stratosphere

Low stratospheric temperatures are known to be responsible for heterogeneous chlorine activation that leads to polar ozone depletion. Here, we discuss the temperature threshold below which substantial chlorine activation occurs. We suggest that the onset of chlorine activation is dominated by reactions on cold binary aerosol particles, without the formation of polar stratospheric clouds (PSCs), i.e. without any significant uptake of HNO3 from the gas phase. Using reaction rates on cold binary aerosol in a model of stratospheric chemistry, a chlorine activation threshold temperature, T-ACL, is derived. At typical stratospheric conditions, T-ACL is similar in value to T-NAT (within 1-2 K), the highest temperature at which nitric acid trihydrate (NAT) can exist. T-NAT is still in use to parameterise the threshold temperature for the onset of chlorine activation. However, perturbations can cause T-ACL to differ from T-NAT: T-ACL is dependent upon H2O and potential temperature, but unlike T-NAT is not dependent upon HNO3. Furthermore, in contrast to T-NAT, T-ACL is dependent upon the stratospheric sulfate aerosol loading and thus provides a means to estimate the impact on polar ozone of strong volcanic eruptions and some geo-engineering options, which are discussed. A parameterisation of T-ACL is provided here, allowing it to be calculated for low solar elevation (or high solar zenith angle) over a comprehensive range of stratospheric conditions. Considering T-ACL as a proxy for chlorine activation cannot replace a detailed model calculation, and polar ozone loss is influenced by other factors apart from the initial chlorine activation. However, T-ACL provides a more accurate description of the temperature conditions necessary for chlorine activation and ozone loss in the polar stratosphere than T-NAT