Stress, Inflammation and Pain: A Potential Role for Monocytes in Fibromyalgia-related Symptom Severity.

The possibility that immunological changes might contribute to symptom severity in fibromyalgia (FM) prompted this proof-of-concept study to determine whether differences in monocyte subpopulations might be present in persons with FM compared with healthy controls. Relationships were assessed by comparing specific symptoms in those with FM (n = 20) and patterns of monocyte subpopulations with healthy age-matched and gender-matched controls (n = 20). Within the same time frame, all participants provided a blood sample and completed measures related to pain, fatigue, sleep disturbances, perceived stress, positive and negative affect and depressed mood (and the Fibromyalgia Impact Questionnaire for those with FM).

The time-course of hindbrain neuronal activity varies according to location during either intraperitoneal or subcutaneous tumor growth in rats: single Fos and dual Fos/dopamine β-hydroxylase immunohistochemistry.

Neuronal activity in the nucleus of the solitary tract, ventrolateral medulla, area postrema, and parabrachial nucleus was studied in rats with intraperitoneal or subcutaneous tumors on the 7th, 14th, 21st, and 28th day after injection of fibrosarcoma tumor cells. We found that the number of Fos and dopamine β-hydroxylase immunopositive neurons differs between animals with intraperitoneal and subcutaneous tumors and also between tumor-bearing rats at different times following injection. Our data indicate that responses of the brainstem structures to peripheral tumor growth depend on the localization as well as the stage of the tumor growth.

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways.

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation.

How might yoga help depression? A neurobiological perspective.

Depression is a prevalent mental health condition worldwide and is the leading cause of disability in adults under the age of 45. Most individuals with major depressive disorder (MDD) report only a 50% decrease in symptoms with the use of the standard allopathic treatments for depression. The mechanisms underlying depression remain poorly understood even though stress and its correlates contribute to multiple aspects of the phenomenology of depression.

Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways.

There is now evidence that depression, as characterized by melancholic symptoms, anxiety, and fatigue and somatic (F&S) symptoms, is the clinical expression of peripheral cell-mediated activation, inflammation and induction of oxidative and nitrosative stress (IO&NS) pathways and of central microglial activation, decreased neurogenesis and increased apoptosis. This review gives an explanation for the multiple "co-morbidities" between depression and a large variety of a) brain disorders related to neurodegeneration, e.g.

Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry.

Pathogen-induced heart rate changes associated with cholinergic nervous system activation.

The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis.

In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression.

Recently, the inflammatory and neurodegenerative (I&ND) hypothesis of depression was formulated (Maes et al., 2009), i.e.

Top-down and bottom-up mechanisms in mind-body medicine: development of an integrative framework for psychophysiological research.

It has become increasingly evident that bidirectional ("top-down and bottom-up") interactions between the brain and peripheral tissues, including the cardiovascular and immune systems, contribute to both mental and physical health. Therapies directed toward addressing functional links between mind/brain and body may be particularly effective in treating the range of symptoms associated with many chronic diseases. In this paper, we describe the basic components of an integrative psychophysiological framework for research aimed at elucidating the underlying substrates of mind-body therapies.

Immune challenge and satiety-related activation of both distinct and overlapping neuronal populations in the brainstem indicate parallel pathways for viscerosensory signaling.

Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake.

Lipopolysaccharide challenge-induced suppression of Fos in hypothalamic orexin neurons: their potential role in sickness behavior.

Orexin neurons in the lateral hypothalamus constitute a critical component in regulation of waking, feeding, and reward-related behaviors. In this study we examined the effects of lipopolysaccharide (LPS) challenge on Fos expression in orexin neurons in rats, to determine changes during sickness in two different behavioral contexts. One cohort of rats was treated with saline or LPS during the daytime, and then tested on an elevated plus maze (EPM) or left in their home cage until sacrifice.

The biobehavioral effects of relaxation guided imagery on maternal stress.

Purpose: The purpose of this pilot study was to investigate the effects of relaxation-guided imagery (R-GI) on perceived stress, anxiety, and corticotropin-releasing hormone (CRH) levels in pregnant African American women beginning in the second trimester.

Methods: This prospective, longitudinal study of 59 women used a controlled randomized experimental design with two groups conducted over 12 weeks. The intervention was a set of three R-GI CDs developed and sequenced to influence study outcomes.

How does immune challenge inhibit ingestion of palatable food? Evidence that systemic lipopolysaccharide treatment modulates key nodal points of feeding neurocircuitry.

Immune challenge induces behavioral changes including reduced ingestion of palatable food. Multiple pathways likely contribute to this effect, including viscerosensory pathways controlling hypothalamic feeding circuits or by influence on "reward" circuitry previously established to control ingestive behavior. To investigate whether the effects of immune challenge may influence this network, we compared brain activation patterns in animals trained to drink a palatable sweetened milk solution and treated systemically with either the immune stimulant lipopolysaccharide (LPS) or saline.

Cranial electrical stimulation: potential use in reducing sleep and mood disturbances in persons with dementia and their family caregivers.

Family caregivers of persons with dementia and their care recipients frequently experience sleep and mood disturbances throughout their caregiving and disease trajectories. Because conventional pharmacologic treatments of sleep and mood disturbances pose numerous risks and adverse effects to elderly persons, the investigation of other interventions is warranted. As older adults use complementary and alternative medicine interventions for the relief of sleep and mood disturbances, cranial electrical stimulation, an energy-based complementary and alternative medicine, may be a viable intervention.

Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior.

The presence of certain bacteria in the gastrointestinal tract influences behavior and brain function. For example, challenge with live Campylobacter jejuni (C. jejuni), a common food-born pathogen, reduces exploration of open arms of the plus maze, consistent with anxiety-like behavior, and activates brain regions associated with autonomic function, likely via a vagal pathway.

Infection-induced viscerosensory signals from the gut enhance anxiety: implications for psychoneuroimmunology.

Infection and inflammation lead to changes in mood and cognition. Although the "classic" sickness behavior syndrome, involving fatigue, social withdrawal, and loss of appetites are most familiar, other emotional responses accompany immune activation, including anxiety. Recent studies have shown that gastrointestinal bacterial infections lead to enhanced anxiety-like behavior in mice.

Organization of immune-responsive medullary projections to the bed nucleus of the stria terminalis, central amygdala, and paraventricular nucleus of the hypothalamus: evidence for parallel viscerosensory pathways in the rat brain.

Immune-responsive neurons in the brainstem, primarily in the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), contribute to a significant drive on forebrain nuclei responsible for brain-mediated host defense responses. The current study investigated the relative contribution of brainstem-derived ascending pathways to forebrain immune-responsive nuclei in the rat by means of retrograde tract tracing and c-Fos immunohistochemistry. Fluorogold was iontophoresed into the bed nucleus of stria terminalis (BST), central nucleus of the amygdala (CEA), paraventricular nucleus of the hypothalamus (PVN), and the pontine lateral parabrachial nucleus (PBL; an important component of ascending viscerosensensory pathways) followed 2 weeks later by intraperitoneal injection of lipopolysaccharide (LPS, 0.

Enhanced neuronal activation in central autonomic network nuclei in aged mice following acute peripheral immune challenge.

Infection is associated with activation in central autonomic nuclei involved in mediating coordinated host defense responses. Aged mice showed exaggerated sickness behavior following peripheral injection of pro-inflammatory bacterial lipopolysaccharide (LPS), but is unknown whether central autonomic network responses are concomitantly increased. To assess whether aged mice exhibit enhanced neural response to LPS, we compared neural responses using c-Fos immunohistochemistry in aged BALB/c mice (22-24 months) with those of young adult peers (3-6 months).

Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium.

Symptoms of anxiety frequently occur concomitant to the development and persistence of inflammatory bowel disease (IBD) in patients. In the present study, we utilized an animal model of IBD, infection with Citrobacter rodentium, to determine whether the infection per se can drive anxiety-like behavior. Nine-week-old CF-1 male mice were challenged orally with either saline or C.

Recommended housing conditions and test procedures can interact to obscure a significant experimental effect.

Routine animal husbandry variables, such as group housing of mice and the order of testing of cage-mates, are currently viewed to be essentially neutral with respect to the outcome of most, if not all, animal-based experiments, including those that utilize behavioral measurements. During the course of experiments that have utilized the elevated plus-maze to examine the ability of a bacterial challenge of mice to induce anxiety-like behavior, due to the activation of various cytokine pathways, we followed the recommendation of laboratory animal care staff to house the mice in pairs. Whenwe testedthe members of the pairs successively, it was found, for the first experimental set, that the behavior that reflects anxiety (time in closed arms) of the first-tested animal differed from that of the second-tested animal for both the experimental and the control animals and, critically, that these changes were in the opposite directions for the controls and the experimental animals, thus obscuring the effect of the experimental manipulation.

Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni.

Abundant evidence now supports the idea that multiple pathways or mechanisms underlie communication from the immune system to the brain. The presence of a variety of mechanisms suggests that they may each contribute something different to immunosensory signaling. For instance, brain mediated immune signal transduction is dependent upon the presence of circulating mediators whereas peripheral sensory nerves are more likely to be important early on in an infection, prior to elevation of circulating cytokines, or in local infections within the terminal fields of these nerves.

Brain response to cecal infection with Campylobacter jejuni: analysis with Fos immunohistochemistry.

Infections with bacterial pathogens can induce increased anxiety-like behaviors in rodents without otherwise noticeable behavioral or physiological symptoms of sickness, as shown with the food-borne pathogen Campylobacter jejuni. This observation implicates the ability of the brain to sense, and respond to, such an infection. We tested our hypothesis that intestinal infection with the gram-negative bacterium C.

Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei.

Peripheral administration of lipopolysaccharide (LPS), a potent activator of the immune system, induces symptoms of behavioral depression, such as social withdrawal, concommitant with increases in c-Fos expression in central autonomic network nuclei. Previous studies implicated vagal visceral sensory nerves in transduction of immune-related signals relevant to for the induction of social withdrawal, a symptom of behavioral depression. Vagal sensory nerves terminate in the dorsal vagal complex (DVC) of the brainstem, a region that functions to integrate visceral signals and may also play a role in modulating arousal and affect.