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Search Results: 1 - 10 of 218272 matches for " Joseph L Riley "
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The Effect of Topical Local Anesthetics on Thermal Pain Sensitivity in Patients with Irritable Bowel Syndrome
Anthony Rodrigues,Christopher D. King,Fong Wong,Joseph L. Riley III,Siegfried Schmidt,Andre P. Mauderli
Pain Research and Treatment , 2012, DOI: 10.1155/2012/438674
Abstract: Generalized hypersensitivity that extends into somatic areas is common in patients with irritable bowel syndrome (IBS). The sensitized state, particularly assessed by experimental methods, is known to persist even during remissions of clinical pain. It was hypothesized that disease-related nociceptive activity in the gut maintains a systemic-sensitized state. The present study evaluated responses to prolonged thermal stimuli maintained at constant temperature or constant pain intensity during stimulation. The effect of topically applied rectal lidocaine on heat sensitivity was also evaluated. The question is whether silencing potential intestinal neural activity (which may not always lead to a conscious pain experience) with lidocaine attenuates sensitization of somatic areas. Tests were also performed where lidocaine was applied orally to control for systemic or placebo effects of the drug. The IBS subjects exhibited a greater sensitivity to somatic heat stimuli compared to controls; however, lidocaine had no discernible effect on sensitization in this sample of IBS patients, where most of the individuals did not have clinical pain on the day of testing. 1. Introduction Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that consists of abdominal pain that can be associated with abnormal bowel movements [1]. The pain often fluctuates and can go into remission [2]. Since natural variation of visceral pain occurs in IBS and other visceral pain disorders, one method to evaluate altered pain processing in IBS is to psychophysically assess responses to controlled experimentally induced stimuli [3, 4]. Like other chronic pain cohorts, IBS patients are often more sensitive to a range of experimentally applied stimuli. For example, distensions of the rectum with a balloon in IBS patients are often reported as more painful and produce pain at lower thresholds compared to individuals without IBS [5–8]. While the underlying pathophysiological mechanism(s) are still unclear, increased sensitivity to visceral pain in IBS patients appears to be influenced by altered processing of afferent information from the gut [7, 8]. In a recent review by Zhou and Verne [3], several models suggest that IBS is associated with physiological changes in gastrointestinal tissue, which usually follow some type of injury or inflammatory insult (e.g., Salmonella infections). One proposed pathway to enhanced pain processing includes changes to intestinal permeability [9, 10] and low-grade inflammation [11], which in turn produces an upegulation of pronociception factors
Immune Biomarker Response Depends on Choice of Experimental Pain Stimulus in Healthy Adults: A Preliminary Study
Yenisel Cruz-Almeida,Christopher D. King,Shannon M. Wallet,Joseph L. Riley III
Pain Research and Treatment , 2012, DOI: 10.1155/2012/538739
Abstract: Few studies in healthy subjects have examined the neuroimmune responses associated with specific experimental pain stimuli, while none has measured multiple biomarkers simultaneously. The aim of the present study was to compare the neuro-immune responses following two common experimental pain stimuli: cold pressor test (CPT) and focal heat pain (FHP). Eight adults participated in two counterbalanced experimental sessions of FHP or CPT with continuous pain ratings and blood sampling before and 30 minutes after the sessions. Despite similar pain intensity ratings (FHP = ; CPT = ; ), CPT and FHP induced different neuro-immune biomarker responses. CPT was accompanied by significant increases in cortisol ( ) and anti-inflammatory cytokine IL-10 ( ) with significant decreases in several pro-inflammatory mediators (IL-1β ( ), IL-12 ( ), TNF-α ( ), and MCP-1 ( )). There were nonsignificant biomarker changes during the FHP session. There were close to significant differences between the sessions for IL-1β ( ), IFN-γ ( ), and IL-12 ( ) with biomarkers decreasing after CPT and increasing after FHP. There were stronger associations between catastrophizing and most biomarkers after CPT compared to FHP. Our results suggest that CPT is a stressful and painful stimulus, while FHP is mostly a painful stimulus. Thus, each experimental pain stimulus can activate different neuro-immune cascades, which are likely relevant for the interpretation of studies in chronic pain conditions. 1. Introduction The cross-talk between the nervous and immune systems is of special interest to pain researchers since immune-derived signaling molecules have been implicated in altered nociception [1] and chronic pain conditions [2] including fibromyalgia [3], osteoarthritis [4], migraine [5], and temporomandibular disorders [6]. The field of pain research relies on the administration of standardized noxious stimulation with response comparisons to translate animal studies to human mechanistic studies, and further translate findings from healthy subjects to patients with chronic pain [7–9]. However, measures of experimental pain have been shown to correlate only moderately across stimulus modalities [1, 10–13]. Also, human imaging studies show a differential pattern of brain activation between two of the most common experimental pain stimuli: the cold pressor test (CPT) and focal heat pain (FHP) stimulation [14]. CPT is mainly mediated by venous nociceptors [15] and cutaneous nociceptors [16], while FHP activates cutaneous nociceptors with varying threshold temperatures [17]. Indeed, the
Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein
Joseph R. Francica,Angel Varela-Rohena,Andrew Medvec,Gabriela Plesa,James L. Riley,Paul Bates
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1001098
Abstract: Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection.
Thermal hypersensitivity in a subset of irritable bowel syndrome patients
QiQi Zhou, Roger B Fillingim, Joseph L Riley III, G Nicholas Verne
World Journal of Gastroenterology , 2009,
Abstract: AIM: To characterize thermal hypersensitivity in patients with constipation- and diarrhea-predominant irritable bowel syndrome (IBS).METHODS: Thermal pain sensitivity was tested among patients with diarrhea-predominant IBS (D-IBS) and constipation-predominant IBS (C-IBS) compared to healthy subjects. A total of 42 patients (29 female and 13 male; mean age 27.0 ± 6.4 years) with D-IBS; 24 patients (16 female and eight male; mean age 32.5 ± 8.8 years) with C-IBS; and 52 control subjects (34 female and 18 male; mean age 27.3 ± 8.0 years) participated in the study. Thermal stimuli were delivered using a Medoc Thermal Sensory Analyzer with a 3 cm × 3 cm surface area. Heat pain threshold (HPTh) and heat pain tolerance (HPTo) were assessed on the left ventral forearm and left calf using an ascending method of limits. The Functional Bowel Disease Severity Index (FBDSI) was also obtained for all subjects.RESULTS: Controls were less sensitive than C-IBS and D-IBS (both at P < 0.001) with no differences between C-IBS and D-IBS for HPTh and HPTo. Thermal hyperalgesia was present in both groups of IBS patients relative to controls, with IBS patients reporting significantly lower pain threshold and pain tolerance at both test sites. Cluster analysis revealed the presence of subgroups of IBS patients based on thermal hyperalgesia. One cluster (17% of the sample) showed a profile of heat pain sensitivity very similar to that of healthy controls; a second cluster (47% of the sample) showed moderate heat pain sensitivity; and a third cluster (36% of the sample) showed a very high degree of thermal hyperalgesia.CONCLUSION: A subset of IBS patients had thermal hypersensitivity compared to controls, who reported significantly lower HPTh and HPTo. All IBS patients had a higher score on the FBDSI than controls. Interestingly, the subset of IBS patients with high thermal sensitivity (36%) had the highest FBDSI score compared to the other two groups of IBS patients.
Slow Temporal Summation of Pain for Assessment of Central Pain Sensitivity and Clinical Pain of Fibromyalgia Patients
Roland Staud, Elizabeth E. Weyl, Joseph L. Riley, Roger B. Fillingim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089086
Abstract: Background In healthy individuals slow temporal summation of pain or wind-up (WU) can be evoked by repetitive heat-pulses at frequencies of ≥.33 Hz. Previous WU studies have used various stimulus frequencies and intensities to characterize central sensitization of human subjects including fibromyalgia (FM) patients. However, many trials demonstrated considerable WU-variability including zero WU or even wind-down (WD) at stimulus intensities sufficient for activating C-nociceptors. Additionally, few WU-protocols have controlled for contributions of individual pain sensitivity to WU-magnitude, which is critical for WU-comparisons. We hypothesized that integration of 3 different WU-trains into a single WU-response function (WU-RF) would not only control for individuals’ pain sensitivity but also better characterize their central pain responding including WU and WD. Methods 33 normal controls (NC) and 38 FM patients participated in a study of heat-WU. We systematically varied stimulus intensities of.4 Hz heat-pulse trains applied to the hands. Pain summation was calculated as difference scores of 1st and 5th heat-pulse ratings. WU-difference (WU-Δ) scores related to 3 heat-pulse trains (44°C, 46°C, 48°C) were integrated into WU-response functions whose slopes were used to assess group differences in central pain sensitivity. WU-aftersensations (WU-AS) at 15 s and 30 s were used to predict clinical FM pain intensity. Results WU-Δ scores linearly accelerated with increasing stimulus intensity (p<.001) in both groups of subjects (FM>NC) from WD to WU. Slope of WU-RF, which is representative of central pain sensitivity, was significantly steeper in FM patients than NC (p<.003). WU-AS predicted clinical FM pain intensity (Pearson’s r = .4; p<.04). Conclusions Compared to single WU series, WU-RFs integrate individuals’ pain sensitivity as well as WU and WD. Slope of WU-RFs was significantly different between FM patients and NC. Therefore WU-RF may be useful for assessing central sensitization of chronic pain patients in research and clinical practice.
Relationships between Irritable Bowel Syndrome Pain, Skin Temperature Indices of Autonomic Dysregulation, and Sensitivity to Thermal Cutaneous Stimulation
Fong Wong,Anthony C. Rodrigues,Christopher D. King,Joseph L. Riley III,Siegfried Schmidt,Charles J. Vierck,Andre P. Mauderli
Pain Research and Treatment , 2010, DOI: 10.1155/2010/949027
Abstract: This study evaluated relationships between irritable bowel syndrome (IBS) pain, sympathetic dysregulation, and thermal pain sensitivity. Eight female patients with diarrhea-predominant IBS and ten healthy female controls were tested for sensitivity to thermal stimulation of the left palm. A new method of response-dependent thermal stimulation was used to maintain pain intensity at a predetermined level (35%) by adjusting thermal stimulus intensity as a function of pain ratings. Clinical pain levels were assessed prior to each testing session. Skin temperatures were recorded before and after pain sensitivity testing. The temperature of palmar skin dropped (1.5 ° C ) when the corresponding location on the opposite hand of control subjects was subjected to prolonged thermal stimulation, but this response was absent for IBS pain patients. The patients also required significantly lower stimulus temperatures than controls to maintain a 35% pain rating. Baseline skin temperatures of patients were significantly correlated with thermode temperatures required to maintain 35% pain ratings. IBS pain intensity was not significantly correlated with skin temperature or pain sensitivity. The method of response-dependent stimulation revealed thermal hyperalgesia and increased sympathetic tone for chronic pain patients, relative to controls. Similarly, a significant correlation between resting skin temperatures and thermal pain sensitivity for IBS but not control subjects indicates that tonic sympathetic activation and a thermal hyperalgesia were generated by the chronic presence of visceral pain. However, lack of a significant relationship between sympathetic tone and ratings of IBS pain casts doubt on propositions that the magnitude of IBS pain is determined by psychological stress. 1. Introduction Irritable bowel syndrome (IBS) is a functional pain disorder with no known etiology but an association with psychological stress [1–3]. Because autonomic output systems of central stress circuits control essential functions of the gut [4–6], stress has been suspect as a cause of IBS [1, 5, 7]. Levels of stress can be revealed as increased sympathetic and/or decreased parasympathetic activity, and IBS patients often have enhanced sympathetic activation [8–14] or reduced parasympathetic activation [8, 14–19] and/or an increased sympathetic/parasympathetic ratio [14, 17, 19, 20]. Numerous factors can change relationships between diagnoses of IBS and levels of autonomic activation including age, duration of chronic pain, gender, profiles of gut disturbance (e.g., abdominal pain
Chronic pain, perceived stress, and cellular aging: an exploratory study
Kimberly T Sibille, Taimour Langaee, Ben Burkley, Yan Gong, Toni L Glover, Chris King, Joseph L Riley, Christiaan Leeuwenburgh, Roland Staud, Laurence A Bradley, Roger B Fillingim
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-12
Abstract: The relationship between chronic pain, stress, and TL was analyzed in 36 ethnically diverse, older adults, half of whom reported no chronic pain and the other half had chronic knee osteoarthritis (OA) pain. Subjects completed a physical exam, radiographs, health history, and psychosocial questionnaires. Blood samples were collected and TL was measured by quantitative polymerase chain reaction (qPCR). Four groups were identified characterized by pain status and the Perceived Stress Scale scores: 1) no pain/low stress, 2) no pain/high stress, chronic pain/low stress, and 4) chronic pain/high stress. TL differed between the pain/stress groups (p = 0.01), controlling for relevant covariates. Specifically, the chronic pain/high stress group had significantly shorter TL compared to the no pain/low stress group. Age was negatively correlated with TL, particularly in the chronic pain/high stress group (p = 0.03).Although preliminary in nature and based on a modest sample size, these findings indicate that cellular aging may be more pronounced in older adults experiencing high levels of perceived stress and chronic pain.A recent Institute of Medicine report documents the public health consequences of chronic pain in America with estimates of 116 million adults affected and costs of $635 billion annually [1]. One of the challenges illuminated in the report is the difficulty in identifying specific pathophysiological targets due to significant variability in the experience of chronic pain. Consequently, biological markers reflecting the physiological burden of chronic pain on an individual system would offer significant clinical and scientific utility.Leukocyte telomere length (TL) is a measure of cellular aging and is associated with age-related disease onset, chronic health conditions, psychosocial stress, and mortality [2-5]. Importantly, recent findings indicate a direct relationship between telomeres and mitochondria, connecting for the first time two major theories of ag
Validating Excised Rodent Lungs for Functional Hyperpolarized Xenon-129 MRI
David M. L. Lilburn, Theodore Hughes-Riley, Joseph S. Six, Karl F. Stupic, Dominick E. Shaw, Galina E. Pavlovskaya, Thomas Meersmann
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073468
Abstract: Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.
Multi-Host Transmission Dynamics of Schistosoma japonicum in Samar Province, the Philippines
Steven Riley ,lène Carabin,Patrick Bélisle,Lawrence Joseph,Veronica Tallo,Ernesto Balolong,A. Lee Willingham III,Tomas J Fernandez Jr.,Ryan O'Neal Gonzales,Remigio Olveda,Stephen T McGarvey
PLOS Medicine , 2008, DOI: 10.1371/journal.pmed.0050018
Abstract: Background Among the 6.7 million people living in areas of the Philippines where infection with Schistosoma japonicum is considered endemic, even within small geographical areas levels of infection vary considerably. In general, the ecological drivers of this variability are not well described. Unlike other schistosomes, S. japonicum is known to infect several mammalian hosts. However, the relative contribution of different hosts to the transmission cycle is not well understood. Here, we characterize the transmission dynamics of S. japonicum using data from an extensive field study and a mathematical transmission model. Methods and Findings In this study, stool samples were obtained from 5,623 humans and 5,899 potential nonhuman mammalian hosts in 50 villages in the Province of Samar, the Philippines. These data, with variable numbers of samples per individual, were adjusted for known specificities and sensitivities of the measurement techniques before being used to estimate the parameters of a mathematical transmission model, under the assumption that the dynamic transmission processes of infection and recovery were in a steady state in each village. The model was structured to allow variable rates of transmission from different mammals (humans, dogs, cats, pigs, domesticated water buffalo, and rats) to snails and from snails to mammals. First, we held transmission parameters constant for all villages and found that no combination of mammalian population size and prevalence of infectivity could explain the observed variability in prevalence of infection between villages. We then allowed either the underlying rate of transmission (a) from snails to mammals or (b) from mammals to snails to vary by village. Our data provided substantially more support for model structure (a) than for model structure (b). Fitted values for the village-level transmission intensity from snails to mammals appeared to be strongly spatially correlated, which is consistent with results from descriptive hierarchical analyses. Conclusions Our results suggest that the process of acquiring mammalian S. japonicum infection is more important in explaining differences in prevalence of infection between villages than the process of snails becoming infected. Also, the contribution from water buffaloes to human S. japonicum infection in the Philippines is less important than has been recently observed for bovines in China. These findings have implications for the prioritization of mitigating interventions against S. japonicum transmission.
A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicum in 50 irrigated and rain-fed villages in Samar Province, the Philippines
Mushfiqur R Tarafder, Ernesto Balolong,lène Carabin, Patrick Bélisle, Veronica Tallo, Lawrence Joseph, Portia Alday, Ryan O'Neil Gonzales, Steven Riley, Remigio Olveda, Stephen T McGarvey
BMC Public Health , 2006, DOI: 10.1186/1471-2458-6-61
Abstract: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis.A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21).We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants.Schistosomiasis japonica is a parasitic zoonosis and an imp
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