Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain

SummaryObjectiveThe present study examined whether local administration of the cannabinoid-2 (CB2) receptor agonist GW405833 could modulate joint nociception in control rat knee joints and in an animal model of osteoarthritis (OA).MethodOA was induced in male Wistar rats by intra-articular injection of sodium monoiodo-acetate with a recovery period of 14 days. Immunohistochemistry was used to evaluate the expression of CB2 and transient receptor potential vanilloid channel-1 (TRPV1) receptors in the dorsal root ganglion (DRG) and synovial membrane of sham- and sodium mono-iodoacetate (MIA)-treated animals. Electrophysiological recordings were made from knee joint primary afferents in response to rotation of the joint both before and following close intra-arterial injection of different doses of GW405833. The effect of intra-articular GW405833 on joint pain perception was determined by hindlimb incapacitance. An in vitro neuronal release assay was used to see if GW405833 caused release of an inflammatory neuropeptide (calcitonin gene-related peptide – CGRP).ResultsCB2 and TRPV1 receptors were co-localized in DRG neurons and synoviocytes in both sham- and MIA-treated animals. Local application of the GW405833 significantly reduced joint afferent firing rate by up to 31% in control knees. In OA knee joints, however, GW405833 had a pronounced sensitising effect on joint mechanoreceptors. Co-administration of GW405833 with the CB2 receptor antagonist AM630 or pre-administration of the TRPV1 ion channel antagonist SB366791 attenuated the sensitising effect of GW405833. In the pain studies, intra-articular injection of GW405833 into OA knees augmented hindlimb incapacitance, but had no effect on pain behaviour in saline-injected control joints. GW405833 evoked increased CGRP release via a TRPV1 channel-dependent mechanism.ConclusionThese data indicate that GW405833 reduces the mechanosensitivity of afferent nerve fibres in control joints but causes nociceptive responses in OA joints. The observed pro-nociceptive effect of GW405833 appears to involve TRPV1 receptors

An Epidemiologic Study of Dental Caries in Preschool Children in the United States by Race and Socioeconomic Level

The prevalence of dental caries in 1,155 white and black preschool children was studied in the United States in 1969 and 1970. The results demonstrated that white children of the lower socioeconomic level had a significantly greater prevalence of dental caries than middle class white children, but a significantly lower prevalence than black children, most of whom represented the lower social class.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67244/2/10.1177_00220345740530023501.pd

The Predictive Validity of the Early Warning System Tool

The Early Warning System (EWS) is a tool developed by the National High School Center to collect data on indicators including attendance, GPA, course failures and credits earned. These indicators have been found to be highly predictive of a student’s likelihood of dropping out of high school in large, urban areas. The EWS tool was studied in two suburban schools. With the exception of attendance data, findings suggest that the indicators and suggested threshold for risk determination are predictive in suburban contexts

Gauge Dependence of Mass and Condensate in Chirally Asymmetric Phase of Quenched QED3

We study three dimensional quenched Quantum Electrodynamics in the bare vertex approximation. We investigate the gauge dependence of the dynamically generated Euclidean mass of the fermion and the chiral condensate for a wide range of values of the covariant gauge parameter $\xi$. We find that (i) away from $\xi=0$, gauge dependence of the said quantities is considerably reduced without resorting to sophisticated vertex {\em ansatze}, (ii) wavefunction renormalization plays an important role in restoring gauge invariance and (iii) the Ward-Green-Takahashi identity seems to increase the gauge dependence when used in conjunction with some simplifying assumptions. In the Landau gauge, we also verify that our results are in agreement with those based upon dimensional regularization scheme within the numerical accuracy available.Comment: 14 pages, 11 figures, uses revte

Landau-Khalatnikov-Fradkin Transformations and the Fermion Propagator in Quantum Electrodynamics

We study the gauge covariance of the massive fermion propagator in three as well as four dimensional Quantum Electrodynamics (QED). Starting from its value at the lowest order in perturbation theory, we evaluate a non-perturbative expression for it by means of its Landau-Khalatnikov-Fradkin (LKF) transformation. We compare the perturbative expansion of our findings with the known one loop results and observe perfect agreement upto a gauge parameter independent term, a difference permitted by the structure of the LKF transformations.Comment: 9 pages, no figures, uses revte

Lattice QCD Simulations in External Background Fields

We discuss recent results and future prospects regarding the investigation, by lattice simulations, of the non-perturbative properties of QCD and of its phase diagram in presence of magnetic or chromomagnetic background fields. After a brief introduction to the formulation of lattice QCD in presence of external fields, we focus on studies regarding the effects of external fields on chiral symmetry breaking, on its restoration at finite temperature and on deconfinement. We conclude with a few comments regarding the effects of electromagnetic background fields on gluodynamics.Comment: 31 pages, 10 figures, minor changes and references added. To appear in Lect. Notes Phys. "Strongly interacting matter in magnetic fields" (Springer), edited by D. Kharzeev, K. Landsteiner, A. Schmitt, H.-U. Ye