Attenuation of myogenic orofacial nociception and mechanical hypersensitivity by viral mediated enkephalin overproduction in male and female rats

BACKGROUND: Clinical studies have tested the use of an engineered herpes virus to treat pain. We hypothesized that subcutaneous injections of an engineered herpes virus that expresses enkephalin would attenuate orofacial nociception and hypersensitivity in male and female rats by a central mechanism. METHODS: Herpes virus was injected subcutaneously around the mouth of male and female rats seventy-two hours before ligatures were placed on the masseter tendon, control treatment groups received either no virus or no ligature. Enkephalin expression was measured and von Frey filament testing and meal duration were utilized to measure mechanical hypersensitivity and the nociceptive response, respectively. Naloxone or naloxone methiodide was administered to rats injected with the enkephalin expressing virus to test if enkephalin was acting peripherally or centrally. RESULTS: Ligature significantly lengthened meal duration and reduced the threshold to von Frey filaments for 18 days. Infection with the enkephalin transgene significantly decreased this response for at least 11 days but only in male rats. Virus injection significantly increased expression of enkephalin in the mental nerve that innervates the mouth region, the trigeminal ganglia and the trigeminal nucleus caudalis but no increase was observed in the masseter nerve after virus injection. Naloxone but not naloxone methiodide reversed the response to the enkephaline expressing virus. CONCLUSIONS: The data suggests that sex should be a considered when using this virus and that viral transfection of the mental nerve with an enkephalin transgene can reduce nociception and hypersensitivity through a central mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12883-015-0285-5) contains supplementary material, which is available to authorized users

Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint

BACKGROUND: Estrogen is known to play role in temporomandibular joint (TMJ) disorders and estrogen effects can be mediated by estrogen receptor (ER) alpha present in the TMJ. Cells expressing the estrogen receptor ERalpha are present in the temporomandibular joint (TMJ) but changes in expression due to estrogen and inflammation have not been characterized. In this study, ERalpha protein content and the number of cells expressing ERalpha was measured in 17 beta-estradiol-treated rats after inflammation was induced in the TMJ. METHODS: Sixteen ovariectomized female rats were divided into two groups such that one group received 17 beta estradiol (E2) and the other was given vehicle (VEH). Groups were then subdivided further, one received injections of saline and the other received Complete Freund's adjuvant (CFA) within the superior joint space of the TMJ. Thus the four groups include no E2/saline, E2/saline, no E2/CFA and E2/CFA. After treatment, the rats were sacrificed, and the TMJ anterior, disc, retrodiscal and synovial tissues were analyzed by western blot and immunocytochemistry. Positive stained cells were counted using a Nikon epifluorescent microscope. RESULTS: The western blot showed that ERalpha protein significantly decreased with inflammation. The number of ERalpha-positive cells in the TMJ was not affected by inflammation or 17 beta-estradiol with exception of the retrodiscal tissue. In the retrodiscal tissue 17 beta-estradiol significantly decreased the number of ERalpha-positive cells but only in a non-inflamed joint. CONCLUSIONS: In conclusion, inflammation and 17 beta-estradiol can modulate ERalpha expression in the TMJ but the effects are tissue specific

Muscle fiber typology is associated with the incidence of overreaching in response to overload training

The aim of this study was to identify markers of training stress and characteristics of middle-distance runners related to the incidence of overreaching following overload training. Twenty-four highly-trained runners (n=16 male; VO2peak=73.3(4.3) mL·kg·min-1; n=8 female, VO2peak=63.2(3.4) mL·kg·min-1) completed 3 weeks of normal training (NormTr), 3 weeks of high-volume training (HVTr; a 10, 20 and 30% increase in training volume each successive week from NormTr), and a 1-week taper (TapTr; 55% exponential reduction in training volume from HVTr week 3). Before, and immediately after each training period, an incremental treadmill-running test was performed, while resting metabolic rate (RMR), subjective fatigue responses and various resting blood biomarkers were assessed. Muscle fiber typology of the gastrocnemius was estimated by quantification of muscle carnosine using proton magnetic resonance spectroscopy and expressed as a z-score relative to a non-athlete control group. Twelve runners were classified as functionally overreached (FOR) following HVTr (decreased running TTE), whereas the other twelve were classified as acutely fatigued (AF; no decrease in running TTE). The FOR group did not demonstrate systematic alterations in RMR, resting blood biomarkers or submaximal exercise responses compared to the AF group. Gastrocnemius carnosine z-score was significantly higher in FOR (-0.44 ± 0.57) compared to AF (-1.25 ± 0.49, p = 0.004, d = 1.53) and was also associated with changes in running TTE from pre- to post-HVTr (r=-0.55, p=0.005) and pre-HVTr to post-TapTr (r=-0.64, p=0.008). Muscle fiber typology is related to the incidence of overreaching and performance super-compensation following increased training volume and a taper

Aromatase Derived Estradiol Within the Thalamus Modulates Pain Induced by Varicella Zoster Virus

Herpes zoster or shingles is the result of varicella zoster virus (VZV) infection and often results in chronic pain that lasts for months after visible symptoms subside. Testosterone often attenuates pain in males. Previous work demonstrates ovarian estrogen effects γ-aminobutyric acid (GABA) signaling in the thalamus, reducing pain but the role of testosterone within the thalamus is currently unknown. Because aromatase affects pain and is present in the thalamus we tested a hypothesis that testosterone converted to estrogen in the thalamus attenuates herpes zoster induced pain. To address this hypothesis, male Sprague-Dawley rats received whisker pad injection of either MeWo cells or MeWo cells containing VZV. To reduce aromatase derived estrogen in these animals we injected aromatase inhibitor letrozole systemically or infused it into the thalamus. To test if estrogen was working through the estrogen receptor (ER) agonist, 4, 4′, 4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was infused concomitant with letrozole. Motivational and affective pain was measured after letrozole and/or PPT treatment. Vesicular GABA transporter (VGAT) is important in pain signaling. Because estrogen effects VGAT expression we measured its transcript and protein levels after letrozole treatment. Virus injection and letrozole significantly increased the pain response but thalamic infusion of PPT reduced zoster pain. Letrozole increased the number of thalamic neurons staining for phosphorylated ERK (pERK) but decreased VGAT expression. The results suggest in male rats aromatase derived estradiol interacts with the ER to increase VGAT expression and increase neuronal inhibition in the thalamus to attenuate VZV induced pain

Search for Supersymmetry at the LHC in Events with Jets and Missing Transverse Energy

A search for events with jets and missing transverse energy is performed in a data sample of pp collisions collected at root s = 7 TeV by the CMS experiment at the LHC. The analyzed data sample corresponds to an integrated luminosity of 1: 14 fb(-1). In this search, a kinematic variable alpha(T) is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. No excess of events over the standard model expectation is found. Exclusion limits in the parameter space of the constrained minimal supersymmetric extension of the standard model are set. In this model, squark masses below 1.1 TeV are excluded at 95% C. L. Gluino masses below 1.1 TeV are also ruled out at 95% C. L. for values of the universal scalar mass parameter below 500 GeV

Study of high-p(T) charged particle suppression in PbPb compared to pp collisions at root s(NN)=2.76 TeV

The transverse momentum spectra of charged particles have been measured in pp and PbPb collisions at root s(NN) = 2.76 TeV by the CMS experiment at the LHC. In the transverse momentum range p(T) = 5-10 GeV/c, the charged particle yield in the most central PbPb collisions is suppressed by up to a factor of 7 compared to the pp yield scaled by the number of incoherent nucleon-nucleon collisions. At higher p(T), this suppression is significantly reduced, approaching roughly a factor of 2 for particles with p(T) in the range p(T) = 40-100 GeV/c