Females with Irritable Bowel Syndrome (IBS) and Temporomandibular Disorder (TMD) are characterized by enhanced sensitivity to experimental pain. One possible explanation for this observation is deficiencies in pain modulation systems like Diffuse Noxious Inhibitory Control (DNIC). In a few studies that used brief stimuli, chronic pain patients demonstrate reduced DNIC. The purpose of this study was to compare sensitivity to prolonged heat pain and the efficacy of DNIC in controls to IBS and TMD patients. Heat pain (experimental stimulus; 44.0-49.0°C), which was applied to left palm, was continuously rated during three 30-second trials across three separate testing sessions under the following conditions: without a conditioning stimulus; during concurrent immersion of the right foot in a 23.0°C (control); and during noxious cold immersion in a (DNIC; 8.0-16.0°C) water bath. Compared to controls, IBS and TMD patients reported increased sensitivity to heat pain and failed to demonstrate pain inhibition due to DNIC. Controls showed a significant reduction in pain during the DNIC session. These findings support the idea that chronic pain patients are not only more pain sensitive and demonstrate reduced pain inhibition by pain, possibly because of dysfunction of endogenous pain inhibition systems.

This study supports the hypothesis that healthy older adults exhibit decreased endogenous pain inhibition compared to younger healthy controls. Twenty-two older adults (56–77 years of age) and 27 controls ages 20–49 participated in five experimental sessions following a training session. Each experimental session consisted of five 60-second trials in which the experimental heat stimulus was presented to the thenar eminence of the left palm with or without a conditioning stimulus (cold-water immersion of the foot). The temperature for the palm (44–49°C) and foot (8–16°C) were customized for each subject. The intensity of experimental pain produced by the contact thermode was continuously measured during the 60-second trial with an electronic visual analogue scale. No significant associations were found between subjects rating of concentration and the overall inhibitory effect. Older subjects failed to demonstrate conditioned pain modulation (CPM) and showed facilitation in the trials using painful concurrent immersion of the foot. A novel aspect of the study was that we recorded “pain offset” (i.e., after sensations) and found that ratings for the older sample decreased at a slower rate than observed for the group of younger adults suggesting increased central sensitization among the older sample. Decrements in CPM could contribute to the greater prevalence of pain in older age. Since a number of neurotransmitter systems are involved in pain modulation, it is possible age-related differences in CPM are due to functional changes in these systems in a number of areas within the neuroaxis.

Myocardial infarction (MI) results in cell death, development of interstitial fibrosis, ventricular wall thinning and ultimately, heart failure. Angiotensin-(1–7) [Ang-(1–7)] has been shown to provide cardioprotective effects. We hypothesize that lentivirus-mediated overexpression of Ang-(1–7) would protect the myocardium from ischaemic injury. A single bolus of 3.5 ×108 transducing units of lenti-Ang-(1–7) was injected into the left ventricle of 5-day-old male Sprague–Dawley rats. At 6 weeks of age, MI was induced by ligation of the left anterior descending coronary artery. Four weeks after the MI, echocardiography and haemodynamic parameters were measured to assess cardiac function. Postmyocardial infarction, rats showed significant decreases in fractional shortening and dP/dt (rate of rise of left ventricular pressure), increases in left ventricular end-diastolic pressure, and ventricular hypertrophy. Also, considerable upregulation of cardiac angiotensin-converting enzyme (ACE) mRNA was observed in these rats. Lentivirus-mediated cardiac overexpression of Ang-(1–7) not only prevented all these MI-induced impairments but also resulted in decreased myocardial wall thinning and an increased cardiac gene expression of ACE2 and bradykinin B2 receptor (BKR2). Furthermore, in vitro experiments using rat neonatal cardiac myocytes demonstrated protective effects of Ang-(1–7) against hypoxia-induced cell death. This beneficial effect was associated with decreased expression of inflammatory cytokines (tumour necrosis factor-α and interleukin-6) and increased gene expression of ACE2, BKR2 and interleukin-10. Our findings indicate that overexpression of Ang-(1–7) improves cardiac function and attenuates left ventricular remodelling post-MI. The protective effects of Ang-(1–7) appear to be mediated, at least in part, through modulation of the cardiac renin–angiotensin system and cytokine production.

Background: Rodent models of orofacial pain typically use methods adapted from manipulations to hind paw; however, limitations of these models include animal restraint and subjective assessments of behavior by the experimenter. In contrast to these methods, assessment of operant responses to painful stimuli has been shown to overcome these limitations and expand the breadth of interpretation of the behavioral responses. In the current study, we used an operant model based on a reward-conflict paradigm to assess nociceptive responses in three strains of mice (SKH1-Hr hr , C57BL/6J, TRPV1 knockout). We previously validated this operant model in rats and hypothesized in this study that wildtype mice would demonstrate a similar thermal stimulus-dependent response and similar operant pain behaviors. Additionally, we evaluated the effects on operant behaviors of mice manipulated genetically (e.g., TRPV1 k.o.) or pharmacologically with resiniferatoxin (RTX), a lesioning agent for TRPV1-expressing neurons. During the rewardconflict task, mice accessed a sweetened milk reward solution by voluntarily position their face against a neutral or heated thermode (37-55°C).

Aim We hypothesize that moderate cardiac-selective overexpression of the angiotensin type 2 receptor (AT2R) would protect the myocardium from ischemic injury after a myocardial infarction (MI) induced by coronary artery ligation. METHODS AND RESULTS For the in vitro studies, Ad-G-AT2R-EGFP was used to overexpress AT2R in rat neonatal cardiac myocytes (RNCM). Expression of AT2R, measured by real-time PCR and immunostaining demonstrated efficient transduction of AT2R in a dose-dependent pattern. AT2R constitutively induced apoptosis in RNCM in dose-dependent patterns. For the in vivo studies, 4×1010 vector genome (vg) of rAAV9-CBA-AT2R was injected into the left ventricle chamber of the heart in 5-day-old Sprague-Dawley rats. At six weeks of age, hearts were harvested and expression of AT2R determined by real time PCR and western blotting. Expression was increased one fold over controls and no apoptosis was detected. Two subsequent in vivo studies were performed. In a prevention study 4×1010 vg of rAAV9-CBA-AT2R was injected into the left ventricle chamber of the heart in 5-day-old Sprague-Dawley rats and MI was induced at six week of age. For a post treatment study 4×1010 vg of rAAV9-CBA-AT2R was administrated to the peri-infarcted myocardium area immediately after MI in six week old animals. For both in vivo studies, cardiac functions were assessed using echocardiography and hemodynamic measurements four weeks after coronary artery ligation. In the in vivo studies the MI rats showed significant decreases in fractional shortening and dP/dt with an increased left ventricular end diastolic pressure and a ventricular hypertrophy. For the prevention study, the moderate cardiac-selective overexpression of AT2R attenuated the above MI-induced impairments and also caused a decrease in ventricular wall thinning. In the post treatment study, the overexpression of AT2R partially reversed the MIinduced cardiac dysfunction. MI also induced the up-regulation of AT1R, ACE, and Collagen I mRNA expression, all of which were attenuated by the overexpression of AT2R. CONCLUSION Moderate cardiac-selective overexpression of AT2R protects heart function from ischemic injury, which may be mediated, at least in part, through modulation of components of the cardiac RAS and collagen levels in the myocardium.

Bacterial colonization of the fixture-abutment interface (FAI) microgap may contribute to increased marginal bone loss. The contribution of loading on bacterial colonization has not been thoroughly evaluated with in vitro experiments. The aim of this study was to evaluate the effect of dynamic loading on the colonization of oral microorganisms in the FAI microgap of dental implants with internal Morse-taper connection. Forty implants were divided into two groups (n = 20/group) based on subjection to dynamic loading conditions. Both Group 1 and 2 were comprised of fixtures that connected to standard abutments and allowed to incubate in a bacterial solution of Escherichia coli . The specimens of Group 2 were loaded with 500 000 cycles of 50 N using a chewing simulator. Following disconnection of fixtures and abutments, microbial samples were taken from the threaded portion of the abutment, plated and cultured under appropriate conditions. One of the 20 implants of Group 1 and 4 of the 20 implants of Group 2 had FAI microgaps colonized by E coli . With the limits of this study, it indicates that implants with internal Morse-taper connection exhibited minimal bacterial penetration down to the threaded part of the FAI and that dynamic loading increases the potential for such bacterial penetration.

Objectives To describe and understand varieties and characteristics of sensitization contributing to hyperalgesia for patients with chronic pain conditions. Methods Thermal stimulation was delivered to the face, forearm and calf of pain-free subjects and individuals with irritable bowel syndrome (IBS), temporomandibular pain disorder (TMD) and fibromyalgia syndrome (FMS). Three second contacts of a preheated thermode occurred at 30 sec. intervals in ascending and then descending series (0.7°C steps). Results Thermal pain ratings during ascending series were greater at each site for individuals diagnosed with chronic pain. Strong pain at the time of testing further enhanced the ratings at all sites, but mild or moderate clinical pain did not have this effect. Thermal pain for all subjects was greater during descending series than during ascending series of arm and leg stimulation. The hypersensitivity during descending series was comparable for pain-free, FMS and TMD subjects but was increased in duration for arm or leg stimulation of FMS subjects. Discussion The widespread sensitization for IBS and TMD subjects does not rely on mechanisms of spatial and temporal summation often invoked to explain widespread hyperalgesia associated with chronic pain. Increased sensitivity during descending series during stimulation of an arm or leg but not the face indicates a propensity for sensitization of nociceptive input to the spinal cord. Abnormally prolonged sensitization for FMS patients reveals a unique influence of widespread chronic pain referred to deep somatic tissues.

Bacterial colonization of the fixture-abutment interface (FAI) microgap may contribute to increased marginal bone loss. The contribution of loading on bacterial colonization has not been thoroughly evaluated with in vitro experiments. The aim of this study was to evaluate the effect of dynamic loading on the colonization of oral micro-organisms in the FAI microgap of dental implants with internal Morse-taper connection. 40 implants were divided into two groups (n=20/group) based on subjection to dynamic loading conditions. Both Group 1 and 2 were comprised of fixtures that connected to standard abutments and allowed to incubate in a bacterial solution of E.Coli. The specimens of Group 2 were loaded with 500000 cycles of 50 N using a chewing simulator. Following disconnection of fixtures and abutments, microbial samples were taken from the threaded portion of the abutment, plated and cultured under appropriate conditions. One of the twenty implants of Group 1 and four of the twenty implants of Group 2 had FAI microgaps colonized by E.coli. With the limits of this study it indicates that implants with internal Morse-taper connection exhibited minimal bacterial penetration down to the threaded part of the FAI and that dynamic loading increases the potential for such bacterial penetration.