Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid containing immune cells to inhibit inflammatory pain

Endogene Opioidpeptide können in bestimmten Regionen des Gehirns als Antwort auf Stress-Stimuli freigesetzt werden. Kürzlich wurden Leukozyten als zusätzliche Quelle endogener Opioide nachgewiesen. Infolge von Stress oder Releasing-Faktoren setzen sie ihre Opioidpeptide frei, welche als endogene Liganden an Opioidrezeptoren auf peripheren sensorischen Nerven binden. Durch die Inhibition exzitatorischer Nerven und/oder Hemmung der Freisetzung exzitatorischer Neuropeptide führen Opioidpeptide zur potenten Hemmung entzündungsbedingter Schmerzen. Die Opioidwirkung bleibt auf das periphere Entzündungsgebiet beschränkt. Die unangenehmen, Opioid-induzierten zentralen Nebenwirkungen wie Atemdepression oder Abhängigkeit treten hierbei nicht auf. Eine wichtige Voraussetzung für die Rekrutierung der Leukozyten aus der Zirkulation in das entzündete Gewebe ist die Expression des intrazellulären Adhäsionsmoleküls 1 (ICAM-1) in Blutgefäßen im entzündeten Gewebe. In der vorliegenden Studie untersuchten wir unter Entzündungsbedingungen den Einfluss peripherer sensorischer und/oder sympathischer Nerven auf die gesteigerte Expression von ICAM-1 und die simultan damit einhergehende Rekrutierung Opioid-haltiger Leukozyten zur Förderung einer potenten Inhibition von Entzündungsschmerzen. Die selektive Degeneration von peripheren sensorischen oder sympathischen Nervenfasern durch ihre entsprechenden Neurotoxine, Capsaicin oder 6-Hydroxydopamin, verringerte signifikant die subkutane Einwanderung ß-Endorphin- (END-) und Met-Enkephalin- (ENK-) haltiger polymorphonukleärer Leukozyten (PMN) (in der frühen Phase) und mononukleärer Leukozyten (in der späten Phase) während der schmerzhaften Freund’s complete Adjuvant- (FCA-) induzierten Hinterpfotenentzündung in Ratten. Calcitonin Gene-Related Peptide- (CGRP-) und Thyrosinhydroxylase- (TH-) immunoreaktive (IR) Nervenfasern befanden sich in engem Kontakt zu ICAM-1-IR Blutgefäßen innerhalb des entzündeten subkutanen Gewebes. Die selektive Degeneration der sensorischen oder sympathischen Nervenfasern schwächte die verstärkte Expression von Gefässendothel ICAM-1 nach intraplantarer (i.pl.) Injektion von FCA ab und führte zur Aufhebung der peripheren endogenen Opioidpeptid- vermittelten Analgesie. Unsere Ergebnisse deuten darauf hin, dass periphere sensorische und sympathische Nerven im Rahmen einer lokalen schmerzhaften Entzündung die Expression von Gefässendothel ICAM-1 steigern und simultan zu einer verstärkten Rekrutierung Opioid-haltiger Leukozyten führen, was infolgedessen die endogene Opioidpeptid-vermittelte Hemmung von Entzündungsschmerzen fördert. Unsere Resultate unterstützen die bereits existierenden Hinweise auf eine enge Verbindung zwischen peripherem Nerven- und Immunsystem.In the central nervous system endogenous opioid peptides can be released following stressful stimuli. Recently, leucocytes have been indentified as an additional source of opioid peptides. In response to stress or releasing factors leucocytes secrete opioid peptides, which are the endogenous ligands of peripheral opioid receptors on sensory nerve terminals. Through their actions on opioid receptors, opioid peptides inhibit excitatory nerves or the release of excitatory neuropeptides and inhibit inflammatory pain. This effect is solely restricted to the peripheral inflamed area. The unwanted, opioid- induced central side-effects as respiratory depression or addiction can thus be avoided. An important prerequisite for the recruitment of opioid-containing leucocytes from the circulation to the inflammatory focus is the expression of vascular intercellular adhesion molecule-1 (ICAM-1) in the inflamed tissue. In the present study, we investigated the contribution of peripheral sensory and/or sympathetic nerves to the upregulated expression of ICAM-1 under inflammatory conditions simultaneously with the increased recruitment of opioid peptide-containing leucocytes to promote the inhibition of inflammatory pain. The selective degeneration of peripheral sensory or sympathetic nerves with their respective neurotoxins, capsaicin or 6-hydroxydopamine, significantly reduced the subcutaneous immigration of ß-endorphin- (END-) and met-enkephalin- (ENK-)-containing polymorphonuclear leukocytes (PMN) (in the early phase) and mononuclear cells (in the late phase) during painful Freund’s complete adjuvant (FCA) hind paw inflammation in rats. Calcitonin gene-related peptide- (CGRP-) and tyrosine hydroxylase-(TH-) immunoreactive (IR) nerve fibers were in close proximitiy to ICAM- 1-IR blood vessels within inflamed subcutaneous paw tissue. Selective degeneration of peripheral sensory or sympathetic nerve fibers significantly attenuated the enhanced expression of vascular endothelium ICAM-1 after intraplantar injection (i.pl.) of FCA and abolished endogenous opioid peptide-mediated peripheral analgesia. Our results indicate an important contribution of peripheral sensory and sympathetic nerves under inflammatory conditions to the enhanced expression of vascular endothelium ICAM-1 and the simultaneously increased recruitment of opioid peptide-containing leucocytes, thus promoting endogenous opioid peptide- mediated inhibition of inflammatory pain. Our data support the existing evidence about a close link between the peripheral nervous system and the immune system

Moral Credentials, Intergroup Attitudes, and Regulatory Focus Interactively Affect Support for Affirmative Action

People generally tend to stay consistent in their attitudes and actions but can feel licensed to act less-than-virtuously when an initial moral action provides an excuse to do so (i.e., moral self-licensing). A handful of studies have tested how relevant initial attitudes moderate the self-licensing effect but yielded mixed findings: Initial attitudes either decrease, increase, or do not influence licensing dynamics. To account for these inconsistent findings, we propose that the effect of attitudes could itself interact with other factors, notably motivational orientation. We conducted two studies taking into account initial attitudes, absence/presence of moral credentials, and participants’ chronic regulatory focus. Drawing from self-completion theory, we expected self-licensing to occur specifically amongst prevention-focused participants holding positive intergroup attitudes. Results supported this prediction. Prevention-focused participants with positive intergroup attitudes supported affirmative action policies to a lesser extent when they had acquired moral credentials, as compared to when they had not (i.e., self-licensing), t(329) = –3.79, p < .001, d = –.42, 95% CI [–.64, –.20]. Additionally, promotion-focused participants holding positive intergroup attitudes supported affirmative action policies to a greater extent when they had acquired moral credentials (i.e., behavioral consistency), t(329) = 2.44, p = .015, d = .27, 95% CI [.05, .49]

Preferential attraction effects with visual stimuli : the role of quantitative versus qualitative visual attributes

Offering an inferior and rarely chosen third (decoy) option to decision makers choosing between two options has a paradoxical effect: It increases the choice share of the option most similar to the decoy. This attraction effect is robust when options are numeric but rarely occurs in humans when options are visual, even though it occurs in animals. Building on psychophysics, we examined two types of visual attributes: quantitative and qualitative. Quantitative visual attributes (e.g., different bottle volumes) can be perceived as magnitudes. Qualitative visual attributes (e.g., different colors), however, do not fall onto a magnitude scale. One can perceive that a bottle’s volume is twice that of another bottle but not that a green bottle’s color is twice that of a red bottle. We observed robust attraction effects for quantitative visual attributes (4,602 adults, 237 college-age participants), which reversed to repulsion effects when the visual attributes were qualitative (6,005 adults)

Brand Suicide? Memory and Liking of Negative Brand Names

Negative brand names are surprisingly common in the marketplace (e.g., Poison perfume; Hell pizza, and Monster energy drink), yet their effects on consumer behavior are currently unknown. Three studies investigated the effects of negative brand name valence on brand name memory and liking of a branded product. Study 1 demonstrates that relative to nonnegative brand names, negative brand names and their associated logos are better recognised. Studies 2 and 3 demonstrate that negative valence of a brand name tends to have a detrimental influence on product evaluation with evaluations worsening as negative valence increases. However, evaluation is also dependent on brand name arousal, with high arousal brand names resulting in more positive evaluations, such that moderately negative brand names are equally as attractive as some non-negative brand names. Study 3 shows evidence for affective habituation, whereby the effects of negative valence reduce with repeated exposures to some classes of negative brand name

Litter, gender and brand: The anticipation of incivilities and perceptions of crime prevalence

This paper isolates litter as a physical incivility in a film-based experiment, demonstrating the impact of litter on participants' anticipation of a wide range of both physical and social incivilities, and on their perceptions of crime prevalence. Such relationships have not previously been examined, partly because litter has rarely been the focus of earlier studies on incivilities. This paper also tests for possible interaction effects in these relationships involving gender (finding no significant interaction), as well as examining whether there is a difference in the anticipation of incivilities and perceptions of crime prevalence between participants exposed to branded as opposed to unbranded litter (finding no difference between the two groups). Litter is often viewed as a tolerable nuisance and not always treated as a priority. This study suggests prioritising funds towards more targeted interventions to reduce litter might result in some ‘quick wins’ – most notably, reducing perceptions of crime prevalenc

Best research practices for using the Implicit Association Test

This is the final version. Available from Springer via the DOI in this record. Interest in unintended discrimination that can result from implicit attitudes and stereotypes (implicit biases) has stimulated many research investigations. Much of this research has used the Implicit Association Test (IAT) to measure association strengths that are presumed to underlie implicit biases. It had been more than a decade since the last published treatment of recommended best practices for research using IAT measures. After an initial draft by the first author, and continuing through three subsequent drafts, the 22 authors and 14 commenters contributed extensively to refining the selection and description of recommendation-worthy research practices. Individual judgments of agreement or disagreement were provided by 29 of the 36 authors and commenters. Of the 21 recommended practices for conducting research with IAT measures presented in this article, all but two were endorsed by 90% or more of those who felt knowledgeable enough to express agreement or disagreement; only 4% of the totality of judgments expressed disagreement. For two practices that were retained despite more than two judgments of disagreement (four for one, five for the other), the bases for those disagreements are described in presenting the recommendations. The article additionally provides recommendations for how to report procedures of IAT measures in empirical articles.Economic and Social Research Council (ESRC