Fibroblast growth factor-induced lens fiber cell elongation is driven by the stepwise activity of Rho and Rac.

The spheroidal shape of the eye lens is crucial for precise light focusing onto the retina. This shape is determined by concentrically aligned, convexly elongated lens fiber cells along the anterior and posterior axis of the lens. Upon differentiation at the lens equator, the fiber cells increase in height as their apical and basal tips migrate towards the anterior and posterior poles, respectively. The forces driving this elongation and migration remain unclear. We found that, in the mouse lens, membrane protrusions or lamellipodia are observed only in the maturing fibers undergoing cell curve conversion, indicating that lamellipodium formation is not the primary driver of earlier fiber migration. We demonstrated that elevated levels of fibroblast growth factor (FGF) suppressed the extension of Rac-dependent protrusions, suggesting changes in the activity of FGF controlling Rac activity, switching to lamellipodium-driven migration. Inhibitors of ROCK, myosin and actin reduced the height of both early and later fibers, indicating that elongation of these fibers relies on actomyosin contractility. Consistent with this, active RhoA was detected throughout these fibers. Given that FGF promotes fiber elongation, we propose that it does so through regulation of Rho activity.

Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology.

Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataracts. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq and CUT&RUN-seq to discover previously unreported mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Furthermore, we identify an epigenetic paradigm of cellular differentiation, defined by progressive loss of the H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.

The length and spacing of river tributaries.

River networks are composed of a mainstem and tributaries. These tributaries dissect landscapes, regulate water and habitat availability, and transport sediment and nutrients. Despite the importance of tributaries, we currently lack theory and data describing whether and how tributary length and spacing varies within watersheds, thereby limiting our ability to accurately describe river network geometry. We address this knowledge gap by analyzing 4,696 tributaries across six landscapes with varying climate, tectonic setting, and lithology. Our results show that both tributary length and spacing systematically increase with downstream distance along the mainstem river, following a power-law scaling. This power-law scaling can be modulated by basin shape, with tributaries becoming shorter and, in some cases, more closely spaced as basin elongate. Furthermore, the power-law scaling may break down in cases where river networks have been disturbed by pervasive faulting, raising the possibility that the scaling we observe is not unique to all branching networks, and instead may be universal across undisturbed fluvial networks. These findings can be used to improve predictions of river network geometry and potentially to distinguish fluvial river networks from other branching networks.

Astrocytic PAR1 and mGluR2/3 control synaptic glutamate time course at hippocampal CA1 synapses.

Astrocytes play an essential role in regulating synaptic transmission. This study describes a novel form of modulation of excitatory synaptic transmission in the mouse hippocampus by astrocytic G-protein-coupled receptors (GPCRs). We have previously described astrocytic glutamate release via protease-activated receptor-1 (PAR1) activation, although the regulatory mechanisms for this are complex. Through electrophysiological analysis and modeling, we discovered that PAR1 activation consistently increases the concentration and duration of glutamate in the synaptic cleft. This effect was not due to changes in the presynaptic glutamate release or alteration in glutamate transporter expression. However, blocking group II metabotropic glutamate receptors (mGluR2/3) abolished PAR1-mediated regulation of synaptic glutamate concentration, suggesting a role for this GPCR in mediating the effects of PAR1 activation on glutamate release. Furthermore, activation of mGluR2/3 causes glutamate release through the TREK-1 channel in hippocampal astrocytes. These data show that astrocytic GPCRs engage in a novel regulatory mechanism to shape the time course of synaptically-released glutamate in excitatory synapses of the hippocampus.

Brain energy metabolism: A roadmap for future research.

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research.

Open-hearted: Preferences for openness in the agreeableness domain.

OBJECTIVE: Open objects encourage interactivity and closed objects discourage it. Repeated experiences with open and closed objects are thought to give rise to spatial concepts that can be used to represent a variety of entities such as societies, others, and the self. The present investigation pursues the idea that preferring that which is open to that which is closed is more compatible with an agreeable mode of interacting with others. METHOD: Three studies (total N = 901) asked participants whether they preferred "open" or "closed" as spatial concepts. Such preferences were linked to variations in agreeableness, peer perceptions, and daily measures of pro-social functioning. RESULTS: Open-preferring, relative to closed-preferring, individuals scored higher in agreeableness (Study 1) and were rated by peers as interpersonally warmer (Study 2). Open preferences varied within and across persons in a daily diary protocol and, in both cases, higher levels of open preference were linked to higher levels of pro-social feeling (Study 3). CONCLUSION: The findings point to a fundamental component of spatial orientation that plays a significant role in encouraging (open) or discouraging (closed) warm, interactive relations with others.

Feelings as a currency of care: A role for agreeableness in emotional reactivity.

OBJECTIVE AND BACKGROUND: The personality trait of agreeableness is linked to a number of core tendencies (e.g., empathy, warmth) that operate in a feeling-based manner. Following considerations of this type, it is proposed that the motivations and characteristics of agreeable individuals, relative to disagreeable individuals, should render them more receptive to emotional events and more responsive to them for this reason. METHOD: Potential links between agreeableness and emotional reactivity were assessed in two studies involving four samples (total N = 517) in which participants continuously rated their feeling states in response to a variety of affective images. RESULTS: Agreeableness did not predict the speed with which emotional reactions began, but agreeable individuals exhibited higher-magnitude peak intensities, regardless of whether stimuli were appetitive (pleasant) or aversive (unpleasant) in nature. CONCLUSIONS: The findings provide novel insights into the personality trait of agreeableness, emotional reactivity phenomena, and the dynamic processes that link agreeableness to emotion.

Distribution of a Remote Medical Exam Device Associated with an Increase in Telehealth Use.

Background: The COVID-19 pandemic accelerated telehealth adoption, but its effects on care quality and costs remain unclear. This study evaluates a remote patient monitoring device's impact on utilization and spending. Methods: A large insurer launched a pilot program involving 2,880 households, representing 6,731 members in three states. Administrative claims data compared participant households to a matched group lacking necessary contact information for participation. Results: Participants had a 0.19 per member (p = 0.03) increase in telehealth visits and a 0.19 per member (p = 0.08) decrease in outpatient in-person visits relative to nonparticipants during the post 6-month period. No significant differences were observed in total outpatient and emergency department visits or total spending. Subgroup analyses revealed a significant reduction in telehealth visits followed by in-person outpatient visits in households with younger children (-9.1%; p < 0.05). Conclusion: This evaluation suggests that remote devices may boost telehealth utilization without increasing costs.

Mr. Gilbert's World Tour: Rethinking Disabled Veterans Across British Imperial Spaces.

This article provides a comparative analysis of the treatment of disabled First World War veterans in 1920s Britain and the simultaneous care of Imperial Pensioners residing in Australia and South Africa via the detailed administrative reports of a British civil servant, G.F. Gilbert. Imperial Pensioners were disabled veteran migrants of the British Army residing overseas. A study of these veteran populations in Australia and South Africa provides two primary insights into the broader historiography of disabled veterans. Firstly, a comparative case study helps to show the way in which cultural notions of disability were part of broader ideas of nation-building overseas. Secondly, the specific disability diagnosis category chosen as a more in-depth case study can further complicate and contradict broader assessments of national responses. This article attempts to build upon recent transnational histories of veterans by transcending national boundaries and homogenous veteran profiles with an extension in methodological scope by providing an intra-national case study via the Imperial Pensioner.

IgG-cleavage protein allows therapeutic AAV gene delivery in passively immunized MPS IIIA mice.

The widespread pre-existing αAAV-Abs in humans pose a critical challenge in translation of AAV gene therapy. The IgG degrading enzyme of Streptococci (IdeS) is demonstrated to specifically cleave IgG of humans and other species (not mouse). This study developed a modified new modified IdeS protein product (IdeSop). When incubated in vitro, IdeSop was shown to completely cleave human and rabbit IgGs within 6 h. To test IdeSop in a disease setting, we established a rabbitized αAAV9-Ab+ mouse by an IV infusion of purified acute αAAV9-Ab+ rabbit IgG into MPS IIIA mice, resulting in serum αAAV9-IgG at 1:6,400 and αAAV9-nAbs at 1:800. IdeSop-Ab-cleavage was shown to be dose-dependent. An IV IdeSop infusion at the effective doses resulted in rapid IgG depletion and clearance of pre-existing αAAV9-IgG and αAAV9-nAbs in rabbitized αAAV9-Abs+ MPS IIIA mice. Importantly, an IV injection of a high dose AAV9-hSGSHop vector (5 × 1013vg/kg) at 24 h post IdeSop treatment led to transduction as effective in αAAV9-Abs+ MPS IIIA mice, as in αAAV9-Abs-negative controls. We believe that transient IdeSop administration may offer a great tool to address the pre-existing-αAAV-Abs for the translation of rAAV gene therapy to treat diseases in humans, making effective rAAV gene therapy available to all patients in need.

Cooperative and competitive regulation of the astrocytic transcriptome by neurons and endothelial cells: Impact on astrocyte maturation.

Astrocytes have essential roles in central nervous system (CNS) health and disease. During development, immature astrocytes show complex interactions with neurons, endothelial cells, and other glial cell types. Our work and that of others have shown that these interactions are important for astrocytic maturation. However, whether and how these cells work together to control this process remains poorly understood. Here, we test the hypothesis that cooperative interactions of astrocytes with neurons and endothelial cells promote astrocytic maturation. Astrocytes were cultured alone, with neurons, endothelial cells, or a combination of both. This was followed by astrocyte sorting, RNA sequencing, and bioinformatic analysis to detect transcriptional changes. Across culture configurations, 7302 genes were differentially expressed by 4 or more fold and organized into 8 groups that demonstrate cooperative and antagonist effects of neurons and endothelia on astrocytes. We also discovered that neurons and endothelial cells caused splicing of 200 and 781 mRNAs, respectively. Changes in gene expression were validated using quantitative PCR, western blot (WB), and immunofluorescence analysis. We found that the transcriptomic data from the three-culture configurations correlated with protein expression of three representative targets (FAM107A, GAT3, and GLT1) in vivo. Alternative splicing results also correlated with cortical tissue isoform representation of a target (Fibronectin 1) at different developmental stages. By comparing our results to published transcriptomes of immature and mature astrocytes, we found that neurons or endothelia shift the astrocytic transcriptome toward a mature state and that the presence of both cell types has a greater effect on maturation than either cell alone. These results increase our understanding of cellular interactions/pathways that contribute to astrocytic maturation. They also provide insight into how alterations to neurons and/or endothelial cells may alter astrocytes with implications for astrocytic changes in CNS disorders and diseases.

Patient perspectives on the use of indwelling pleural catheters in malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.

Influence of Wildfire on Urban Ozone: An Observationally Constrained Box Modeling Study at a Site in the Colorado Front Range.

Increasing trends in biomass burning emissions significantly impact air quality in North America. Enhanced mixing ratios of ozone (O3) in urban areas during smoke-impacted periods occur through transport of O3 produced within the smoke or through mixing of pyrogenic volatile organic compounds (PVOCs) with urban nitrogen oxides (NOx = NO + NO2) to enhance local O3 production. Here, we analyze a set of detailed chemical measurements, including carbon monoxide (CO), NOx, and speciated volatile organic compounds (VOCs), to evaluate the effects of smoke transported from relatively local and long-range fires on O3 measured at a site in Boulder, Colorado, during summer 2020. Relative to the smoke-free period, CO, background O3, OH reactivity, and total VOCs increased during both the local and long-range smoke periods, but NOx mixing ratios remained approximately constant. These observations are consistent with transport of PVOCs (comprised primarily of oxygenates) but not NOx with the smoke and with the influence of O3 produced within the smoke upwind of the urban area. Box-model calculations show that local O3 production during all three periods was in the NOx-sensitive regime. Consequently, this locally produced O3 was similar in all three periods and was relatively insensitive to the increase in PVOCs. However, calculated NOx sensitivities show that PVOCs substantially increase O3 production in the transition and NOx-saturated (VOC-sensitive) regimes. These results suggest that (1) O3 produced during smoke transport is the main driver for O3 increases in NOx-sensitive urban areas and (2) smoke may cause an additional increase in local O3 production in NOx-saturated (VOC-sensitive) urban areas. Additional detailed VOC and NOx measurements in smoke impacted urban areas are necessary to broadly quantify the effects of wildfire smoke on urban O3 and develop effective mitigation strategies.

Percutaneous transluminal angioplasty and/or stenting for the treatment of basilar artery stenosis: a systematic review and meta-analysis.

PURPOSE: Basilar artery stenosis (BAS) carries high morbidity and mortality, with variable outcomes after endovascular treatments. We systematically reviewed the literature on percutaneous transluminal angioplasty and/or stenting (PTAS) for BAS. METHODS: PubMed, EMBASE, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include prospective/retrospective cohort studies describing PTAS for BAS. Pooled rates of intervention-related complications and outcomes were analyzed with random-effect model meta-analyses. RESULTS: We included 25 retrospective cohort studies comprising 1016 patients. All patients were symptomatic, presenting with transient ischemic attack or ischemic stroke. BAS frequently involved the middle basilar artery (51.4%), mostly classified as Mori-B (57.4%). PTAS for BAS was indicated in severe (≥ 50-70%), symptomatic BAS refractory to dual antiplatelet therapy. Patients underwent angioplasty (95.5%) and/or stenting (92.2%), preferably using Wingspan or Apollo stents. Median baseline BAS was 81% (range, 53-99%), while median post-intervention BAS was 13% (0-75%). Actuarial rates of successful intervention and "good" final outcome were 100% (95% CI: 100-100%) and 89% (95% CI: 85-93%). Intervention-related recurrent ischemic stroke occurred in 85 patients (8.3%) with actuarial rates of 5% (95% CI: 4-7%), differentiated into perforator (5.4%), in-stent (2.6%), and embolic (0.4%). Actuarial rates of intervention-related dissection, restenosis, and death were 0% (95% CI: 0-0%), 1% (95% CI: 0-1%), and 0% (95% CI: 0-2%). CONCLUSION: Elective PTAS appears to be safe and effective in selected patients with medically refractory, severe, symptomatic, and non-acute BAS. Different stent types and angioplasty-assisted procedures should be considered based on specific clinico-radiological characteristics of the lesions. Future randomized controlled trials are required to corroborate these findings.

Examining Physical and Cognitive Function in Chronic Low Back Pain Through the Use of a Multisystem Resilience Framework.

OBJECTIVES: Chronic pain results in significant impairment in older adults, yet some individuals maintain adaptive functioning. Limited research has considered the role of positive resources in promoting resilience among older adults. Likewise, these factors have largely been examined independently. We aimed to identify resilience domains based on biopsychosocial factors and explore whether resilience phenotypes vary across sleep disturbance, fatigue, and cognitive function. METHODS: Sixty adults (ages ≥60 years) with chronic low back pain completed measures of psychological, health, and social functioning. On the basis of previously published analyses, principal-components analysis was conducted to create composite domains for these measures, followed by cluster analysis to identify phenotypes. RESULTS: Four profiles emerged: Cluster 1, with high levels of psychosocial and health-related functioning; Cluster 2, with high health-related functioning and low psychosocial functioning; Cluster 3, with high psychosocial functioning and poorer health; and Cluster 4, with low levels of functioning across all domains. Significant differences across cluster membership emerged for sleep disturbance (ηp2 = 0.29), fatigue (ηp2 = 0.29), and cognitive abilities (ηp2 = 0.47). Individuals with the highest levels of resilience demonstrated more optimal outcomes in sleep and fatigue (P values ≤0.001) than did individuals with a less resilient phenotype. Furthermore, the High-Resilience group (Cluster 1) and the High Psychosocial / Low Health group (Cluster 3) had lower cognitive impairment than did the High Health / Low Psychosocial group (Cluster 2) and the Low-Resilience group (Cluster 4) (P values ≤0.009). CONCLUSIONS: A higher array of protective resources could buffer against the negative sequelae associated with chronic low back pain. These exploratory findings support the multidimensional nature of resilience and suggest that targeting resilience from a multisystem perspective might help to optimize interventions for older adults with chronic pain.

Polypharmacy in older patients presenting to a tertiary regional health service: identifying correlations between demographics, presentations and length of stay.

This study aimed to describe hospital admissions in patients experiencing polypharmacy and evaluate the effects of demographic factors on length of stay (LOS) and polypharmacy. We found that increasing age is associated with increasing polypharmacy rates but decreasing LOS. Females were more likely to experience higher rates of polypharmacy, but males were more likely to have longer LOS. First Nations peoples had higher rates of polypharmacy and longer LOS. Future projects investigating deprescribing methods are critical.

Tolerability of pharmacological agents in the treatment of headache following brain injury: a scoping review.

BACKGROUND: While systematic reviews have examined medication effectiveness for post-traumatic headache (PTH), they have not assessed tolerability. OBJECTIVE: To conduct a scoping review to characterize the adverse effects of pharmacotherapy for PTH. METHODS: CINAHL, CMA Infobase, Cochrane Library, Embase, Epistemonikos, MEDLINE, PEDro, PsycInfo, Scopus, SportDiscus, TRIP and the University of York Center for Reviews and Dissemination were searched. Studies meeting these criteria were included 1) English language, 2) involved humans with traumatic brain injury (TBI), 3) a medication for PTH was administered and 4) reported tolerability outcomes. Author(s), publication year, country of origin, study design, sample demographics, medication type, comparator, dose, treatment duration, adverse effect type and rate, discontinuation rate, and effectiveness outcomes were extracted. RESULTS: The search yielded 2941 records; 11 studies were included (n = 324 subjects). All subjects had mild TBI except for one with moderate TBI. The following therapies were examined 1) abortive (dihydroergotamine N = 1; metoclopramide N = 1; indomethacin N = 3), 2) prophylactic (divalproex sodium N = 1; amantadine N = 1; erenumab N = 2; amitriptyline N = 2). No serious adverse effects occurred. Observed adverse effects overlap with common symptoms of TBI. CONCLUSION: The unique needs of people with TBI must be considered when instituting pharmacotherapy. More studies specifically evaluating medication tolerability in PTH are needed.

Should Sedillot's triangle be used for central venous cannulation? A cadaveric study.

Central venous access remains an integral part of perioperative and intensive care, and several methods have been described to locate the internal jugular vein (IJV) prior to cannulation. The apex of Sedillot's triangle between the manubrial and clavicular heads of the sternocleidomastoid (SCM) muscle is a commonly used anatomical landmark for a central percutaneous approach to the IJV, but the literature highlights failures and complications when adopting this method. This cadaveric study was designed to investigate the usefulness of Sedillot's triangle to locate the IJV. Sixty-one cadavers were used for investigation at the University of Cambridge Human Anatomy Centre. Sedillot's triangle was dissected and a pin was inserted in a sagittal plane at the apex of the triangle. The location of the pin in relation to the IJV was recorded. The distance between the sternal and clavicular heads of SCM was also measured. In total, the pin inserted at the apex of Sedillot's triangle pierced the IJV in 72/117 (61.5%) of dissections, with 71.4% on the right and 52.5% on the left. There was important variation in SCM anatomy, and there was no gap between its two heads in 12% of the neck dissections. We demonstrate an overall poor success rate of the central percutaneous approach using Sedillot's triangle, although our findings are limited being a simulated cadaveric study. We support education and use of ultrasound in addition to landmark techniques to aid the safe insertion of central venous catheters.

Rapid Regulation of Glutamate Transport: Where Do We Go from Here?

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). A family of five Na+-dependent transporters maintain low levels of extracellular glutamate and shape excitatory signaling. Shortly after the research group of the person being honored in this special issue (Dr. Baruch Kanner) cloned one of these transporters, his group and several others showed that their activity can be acutely (within minutes to hours) regulated. Since this time, several different signals and post-translational modifications have been implicated in the regulation of these transporters. In this review, we will provide a brief introduction to the distribution and function of this family of glutamate transporters. This will be followed by a discussion of the signals that rapidly control the activity and/or localization of these transporters, including protein kinase C, ubiquitination, glutamate transporter substrates, nitrosylation, and palmitoylation. We also include the results of our attempts to define the role of palmitoylation in the regulation of GLT-1 in crude synaptosomes. In some cases, the mechanisms have been fairly well-defined, but in others, the mechanisms are not understood. In several cases, contradictory phenomena have been observed by more than one group; we describe these studies with the goal of identifying the opportunities for advancing the field. Abnormal glutamatergic signaling has been implicated in a wide variety of psychiatric and neurologic disorders. Although recent studies have begun to link regulation of glutamate transporters to the pathogenesis of these disorders, it will be difficult to determine how regulation influences signaling or pathophysiology of glutamate without a better understanding of the mechanisms involved.

Analgesic effects of alcohol in adults with chronic jaw pain.

BACKGROUND: Although recent literature provides promising support for the analgesic properties of alcohol, potential differences in alcohol analgesia as a function of chronic pain status are not well understood. Thus, this study examined chronic pain status as a potential moderator of alcohol analgesia and distinguished between multiple aspects of pain experience and sensitivity: pain threshold, pain intensity, pain unpleasantness, and perceived relief. METHODS: Social drinkers with (N = 19) and without (N = 29) chronic jaw pain completed two testing sessions in a counterbalanced order: alcohol (target BrAC = 0.08 g/dl) and placebo. In each, pressure algometry was performed at the insertion of the masseter. Alcohol analgesia was assessed by examining the main and interactive effects of beverage condition, pressure level (4, 5, or 6 pound-feet [lbf]), and chronic jaw pain status (chronic pain vs. pain-free control) on quantitative sensory testing measures and pain relief ratings following noxious stimuli. RESULTS: Analyses indicated significant increases in pain threshold and pain relief and reductions in pain unpleasantness and pain intensity, under the alcohol condition. Chronic pain participants demonstrated lower pain thresholds and greater pain intensity and pain unpleasantness ratings than controls. There were no interactive effects of alcohol and pain conditions on any pain measure. CONCLUSIONS: Findings provide experimental evidence of alcohol's analgesic and pain-relieving effects and suggest that these effects do not significantly differ by chronic pain status. Individuals, who self-medicate pain via alcohol consumption, irrespective of pain status, may be at increased risk to engage in hazardous drinking patterns and thus experience adverse alcohol-related consequences.