Evaluation of different drug classes on transient sciatic nerve injury-depressed marble burying in mice

A great need exists for the identification of new effective analgesics to treat sustained pain. However, most preclinical nociceptive assays measure behavioral responses evoked by noxious stimuli (i.e., pain-stimulated behavior), which presents a challenge to distinguish between motor impairing and antinociceptive effects of drugs. Here, we demonstrate that chronic constriction injury of the sciatic nerve (CCI) elicits common pain-stimulated responses (i.e., mechanical allodynia and thermal hyperalgesia) as well as reduces marble burying/digging behaviors that occur during the early stages of the neuropathy and resolve within one week. Whereas drugs representing distinct classes of analgesics (i.e., morphine, valdecoxib, and gabapentin) reversed both CCI-induced and CCI-depressed nociceptive measures, diazepam lacked antinociceptive effects in all assays and the kappa opioid receptor agonist U69593 reversed pain-stimulated, but not pain-depressed behaviors. In addition, we tested drugs targeting distinct components of the endocannabinoid system, including agonists at cannabinoid receptors type 1 (CB1) and type 2 (CB2), as well as inhibitors of the endocannabinoid regulating enzymes fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL). Each of these drugs reversed all CCI-induced nociceptive measures, with the exception of the FAAH inhibitor that reversed pain-stimulated behaviors, only. These findings support the use of the mouse marble-burying assay as a model of pain-depressed behavior within the first week of sciatic nerve injury to examine candidate analgesics. These data also support existing preclinical research that cannabinoid receptor agonists and inhibitors of endocannabinoid regulating enzymes merit consideration for the treatment of pain.Molecular Physiolog

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

Peer reviewe

Search for neutral resonances decaying into a Z boson and a pair of b jets or τ leptons

A search is performed for a new resonance decaying into a lighter resonance and a Z boson. Two channels are studied, targeting the decay of the lighter resonance into either a pair of oppositely charged τ leptons or a bb‾ pair. The Z boson is identified via its decays to electrons or muons. The search exploits data collected by the CMS experiment at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.8 fb −1 . No significant deviations are observed from the standard model expectation and limits are set on production cross sections and parameters of two-Higgs-doublet models

Search for a low-mass pseudoscalar Higgs boson produced in association with a bb⁻ pair in pp collisions at √s=8 TeV

A search is reported for a light pseudoscalar Higgs boson decaying to a pair of tau leptons, produced in association with a b (b) over bar pair, in the context of two-Higgs-doublet models. The results are based on pp collision data at a centre-of-mass energy of 8 TeV collected by the CMS experiment at the LHC and corresponding to an integrated luminosity of 19.7 fb(-1). Pseudoscalar boson masses between 25 and 80 GeV are probed. No evidence for a pseudoscalar boson is found and upper limits are set on the product of cross section and branching fraction to tau pairs between 7 and 39 pb at the 95% confidence level. This excludes pseudoscalar A bosons with masses between 25 and 80 GeV, with SM-like Higgs boson negative couplings to down-type fermions, produced in association with bb pairs, in Type II, two-Higgs-doublet models. (C) 2016 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommonnorg/licensesiby/4.01)

Phenomenological MSSM interpretation of CMS searches in pp collisions at √s=7 and 8 TeV

Searches for new physics by the CMS collaboration are interpreted in the framework of the phenomenological minimal supersymmetric standard model (pMSSM). The data samples used in this study were collected at root s = 7 and 8 TeV and have integrated luminosities of 5.0 fb(-1) and 19.5 fb(-1), respectively. A global Bayesian analysis is performed, incorporating results from a broad range of CMS supersymmetry searches, as well as constraints from other experiments. Because the pMSSM incorporates several well-motivated assumptions that reduce the 120 parameters of the MSSM to just 19 parameters defined at the electroweak scale, it is possible to assess the results of the study in a relatively straightforward way. Approximately half of the model points in a potentially accessible subspace of the pMSSM are excluded, including all pMSSM model points with a gluino mass below 500 GeV, as well as models with a squark mass less than 300 GeV. Models with chargino and neutralino masses below 200 GeV are disfavored, but no mass range of model points can be ruled out based on the analyses considered. The nonexcluded regions in the pMSSM parameter space are characterized in terms of physical processes and key observables, and implications for future searches are discussed

Search for massive WH resonances decaying into the l nu b(b)over-bar final state at root s=8 TeV

Peer reviewe