Why PNI scientists need to engage in exploratory hypothesis-generating biomarker studies.

Multi-omics research is developing rapidly, offering extensive sample analysis options and advanced statistical solutions to identify and understand complex networks of biomarkers. This review encourages groups in the psychoneuroimmunology field with limited experience in research to embrace these advances. Cross-sectional studies can leverage existing sample collections to provide unique information that complements longitudinal studies, providing insights into which biological systems may warrant further investigation and building fundamental mechanistic knowledge of biological networks.

Associations between sickness behavior, but not inflammatory cytokines, and psychiatric comorbidity in chronic pain.

Objectives: Approximately one in five adults experiences chronic pain, often in co-occurrence with depression, insomnia, anxiety, and lower self-rated health. Elevated levels of cytokines, e.g.

Olfactory Cues of Naturally Occurring Systemic Inflammation: A Pilot Study of Seasonal Allergy.

Introduction: In an attempt to avoid contact with infectious individuals, humans likely respond to generalized rather than specific markers of disease. Humans may thus perceive a noninfectious individual as socially less attractive if they look (e.g.

How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review.

The immune system and the central nervous system exchange information continuously. This communication is a prerequisite for adaptive responses to physiological and psychological stressors. While the implicate relationship between inflammation and pain is increasingly recognized in clinical cohorts, the underlying mechanisms and the possibilities for pharmacological and psychological approaches aimed at neuro-immune communication in pain are not fully understood yet.

Human scent as a first-line defense against disease.

Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals' body odor be perceived as more aversive (intense, unpleasant, and disgusting).

Links between brain neuroimaging and blood inflammatory markers in urological chronic pelvic pain syndrome.

Urological chronic pelvic pain syndrome (UCPPS) is a debilitating painful condition with unclear etiology. Prior researchers have indicated that compared to healthy controls, patients with UCPPS demonstrated altered brain activity. Researchers have also shown that in UCPPS, several blood inflammatory markers relate to clinical variables of pain, fatigue, and pain widespreadness.

Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain.

Chronic pain is characterized by high psychological comorbidity, and diagnoses are symptom-based due to a lack of clear pathophysiological factors and valid biomarkers. We investigate if inflammatory blood biomarker signatures are associated with pain intensity and psychological comorbidity in a mixed chronic pain population. Eighty-one patients (72% women) with chronic pain (>6 months) were included.

Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain.

Background: The medical and scientific communities struggle to understand chronic pain and find effective treatments. Multimodal approaches are encouraging but show significant individual differences. Methods: Seventy-eight persons (56 women) with chronic pain received Acceptance and Commitment Therapy and provided blood samples before and after treatment.

Evaluating the construct validity and internal consistency of the Sickness Questionnaire in a Swedish sample of adults with longstanding pain.

Objectives: Low-grade inflammation is a possible contributing factor in the development and persistence of chronic primary pain syndromes. Related to inflammatory activity is sickness behavior, a set of behavioral responses including increased pain sensitivity, fatigue, malaise, fever, loss of appetite, as well as depressive behavior and anhedonia. To capture these behavioral responses and their relation to longstanding pain, psychometrically sound self-report questionnaires are needed.

Anterior insula morphology and vulnerability to psychopathology-related symptoms in response to acute inflammation.

Introduction: The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology-related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses.

Relationship Between Blood Cytokine Levels, Psychological Comorbidity, and Widespreadness of Pain in Chronic Pelvic Pain.

Low-grade inflammation has been implicated in the etiology of depression, long-term fatigue and chronic pain. TNFα and IL-6 are perhaps the most studied pro-inflammatory cytokines in the field of psychoneuroimmunology. The purpose of our study was to further investigate these relationships in patients with chronic pelvic pain specifically.

Objective and Subjective Sleep in Rheumatoid Arthritis and Severe Seasonal Allergy: Preliminary Assessments of the Role of Sickness, Central and Peripheral Inflammation.

Introduction: Disturbed sleep in inflammatory disorders such as allergy and rheumatoid arthritis (RA) is common and may be directly or indirectly related to disease processes, but has not been well characterized in these patient groups, especially not with objective methods.

Aim: The present study aimed to characterize objective and subjective sleep in patients with allergy or RA using sleep diaries, one-channel EEG and actigraphy. It also aimed to investigate if sleep measures were associated with central immune activation, assessed using translocator protein (TSPO) positron emission tomography, as well as cytokine markers of peripheral inflammation and disease-specific symptoms or general symptoms of sickness.

Comparison of bacterial lipopolysaccharide-induced sickness behavior in rodents and humans: Relevance for symptoms of anxiety and depression.

Increasing evidence from animal and human studies suggests that inflammation may be involved in mood disorders. Sickness behavior and emotional changes induced by experimental inflammatory stimuli have been extensively studied in humans and rodents to better understand the mechanisms underlying inflammation-driven mood alterations. However, research in animals and humans have remained compartmentalized and a comprehensive comparison of inflammation-induced sickness and depressive-like behavior between rodents and humans is lacking.

Neuroimmune modulation of pain across the developmental spectrum.

Today's treatment for chronic pain is inadequate, and novel targets need to be identified. This requires a better understanding of the mechanisms involved in pain sensitization and chronification. In this review, we discuss how peripheral inflammation, as occurs during an infection, modulates the central pain system.

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation.

Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects.

Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans.

Inflammation is believed to be a central mechanism in the pathophysiology of fatigue. While it is likely that dynamic of the fatigue response after an immune challenge relates to the corresponding cytokine release, this lacks evidence. Although both fatigue and sleepiness are strong signals to rest, they constitute distinct symptoms which are not necessarily associated, and sleepiness in relation to inflammation has been rarely investigated.

The effect of a transient immune activation on subjective health perception in two placebo controlled randomised experiments.

Background: Patient-reported outcomes predict mortality and play increasingly important roles in care, but factors that modify central measures such as health ratings have been little investigated. Building on designated immune-to-brain pathways, we aimed to determine how a short-term induced inflammation response impacts self-reported health status.

Methods: Lipopolysaccharide injections were used to provoke acute systemic inflammatory responses in healthy men and women and were compared to placebo in two double-blind randomized experiments.

Detection of Inflammation via Volatile Cues in Human Urine.

Contagious disease is a major threat to survival, and the cost of relying on the immune system to defeat pathogens is high; therefore, behavioral avoidance of contagious individuals is arguably an adaptive strategy. Animal findings demonstrate the ability to detect and avoid sick individuals by the aid of olfactory cues, and a recent study indicated that human axillary odor also becomes more aversive as a function of immune activation. By injecting healthy human participants with lipopolysaccharide (0.

Sex differences in how inflammation affects behavior: What we can learn from experimental inflammatory models in humans.

Human models demonstrate that experimental activation of the innate immune system has profound effects on brain activation and behavior, inducing fatigue, worsened mood and pain sensitivity. It has been proposed that inflammation is a mechanism involved in the etiology and maintenance of depression, chronic pain and long-term fatigue. These diseases show a strong female overrepresentation, suggesting that a better understanding of sex differences in how inflammation drives behavior could help the development of individualized treatment interventions.

Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy: A [C]PBR28 PET study.

Allergy is associated with non-specific symptoms such as fatigue, sleep problems and impaired cognition. One explanation could be that the allergic inflammatory state includes activation of immune cells in the brain, but this hypothesis has not been tested in humans. The aim of the present study was therefore to investigate seasonal changes in the glial cell marker translocator protein (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in allergy.

Lifetime Modulation of the Pain System Neuroimmune and Neuroendocrine Interactions.

Chronic pain is a debilitating condition that still is challenging both clinicians and researchers. Despite intense research, it is still not clear why some individuals develop chronic pain while others do not or how to heal this disease. In this review, we argue for a multisystem approach to understand chronic pain.

Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms.

Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development.

Health anxiety in a disease-avoidance framework: Investigation of anxiety, disgust and disease perception in response to sickness cues.

Severe health anxiety is characterized by a debilitating fear of somatic illness, and avoidance of disease-related stimuli plays a key role in the maintenance of the disorder. The aim of this study was to investigate severe health anxiety within an evolutionary disease-avoidance framework. We hypothesized that, compared to healthy controls, participants with severe health anxiety would perceive others as sicker, more contagious, and less attractive.