Publications by authors named "Stohler C"

Background: Few studies have evaluated the effects of structured early mobilization (EM) protocols on the level of mobilization in critical care patients.

Objective: To evaluate the impact of a structured EM protocol on the level of mobilization, muscle strength, and the level of activities of daily living (LADL) after intensive care unit (ICU) and hospital discharge.

Methods: This randomized clinical trial (U1111-1245-4840) included adults patients who were randomized into two groups: intervention ( = 40) and control ( = 45).

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Objective: To compare adherence to protective mechanical ventilation (MV) parameters in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies.

Design: Multiple prospective cohort study.

Setting: Two Brazilian cohorts of ARDS patients were evaluated.

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The results of this study can help key stakeholders, such as health care facilities, educational and research institutions, insurance companies, and governmental bodies, plan future activities and policies on dental practice and education.

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Behavioral conditioning and expectation can have profound impact on animal and human physiology. Placebo, administered under positive expectation in clinical trials, can have potent effects on disease pathology, obscuring active medications. Emerging evidence suggests placebo-responsive neurotransmitter systems (e.

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Over the past year our attention has inevitably been on the coronavirus pandemic, the health and welfare of our families, patients, and office staffs as well as the re-opening of our dental practices. In addition, the opioid crisis continues, is very likely to worsen as a result of the pandemic and continues to be a challenge to Dentistry. National public health issues and healthcare disparities continue and have created a global concern for providing evidence-based, adequate pain management in the dental setting.

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Clinicians have the dilemma of prescribing opioid or nonopioid analgesics to chronic pain patients; however, the impact of pain on our endogenous µ-opioid system and how our genetic profile (specifically catechol-O-methyltransferase [] polymorphisms) impacts its activation are currently unknown. Twelve chronic temporomandibular disorder (TMD) patients and 12 healthy controls (HCs) were scanned using positron emission tomography (PET) with [C]carfentanil, a selective radioligand for µ-opioid receptors (µORs). The first 45 min of each PET measured the µOR nondisplaceable binding potential (BP) at resting state, and the last 45 min consisted of a 20-min masseteric pain challenge with an injection of 5% hypertonic saline.

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The prefrontal cortex (PFC) is not only important in executive functions, but also pain processing. The latter is dependent on its connections to other areas of the cerebral neocortex, hippocampus, periaqueductal gray (PAG), thalamus, amygdala, and basal nuclei. Changes in neurotransmitters, gene expression, glial cells, and neuroinflammation occur in the PFC during acute and chronic pain, that result in alterations to its structure, activity, and connectivity.

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The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A (iPLA) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, maprotiline.

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Unlabelled: Back pain is common in the general population, but only a subgroup of back pain patients develops a disabling chronic pain state. The reasons for this are incompletely understood, but recent evidence implies that both preexisting and pain-related variations in the structure and function of the nervous system may contribute significantly to the development of chronic pain. Here, we addressed the role of striatal dopamine (DA) D2/D3 receptor (D2/D3R) function in chronic non-neuropathic back pain (CNBP) by comparing CNBP patients and healthy controls using PET and the D2/D3R-selective radioligand [(11)C]raclopride.

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Article Synopsis
  • Mu-opioid receptors play a key role in pain management and may help identify biomarkers for pain conditions and treatment responses.
  • Genetic variations in the μ-opioid receptor gene (OPRM1), specifically the A118G polymorphism, impact pain perception and placebo responses in individuals, with G carriers showing distinct differences in neurotransmitter activity.
  • The study found that G carriers exhibit lower μ-opioid receptor availability and greater emotional disturbances under placebo, suggesting that genetic factors can influence both pain experiences and the effectiveness of placebo treatments.
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Evidence in animal models suggests IL-1 family cytokines interact with central endogenous opioid neurotransmitter systems, inducing or perpetuating pathological states such as persistent pain syndromes, depression, substance use disorders, and their comorbidity. Understanding these interactions in humans is particularly relevant to understanding pathological states wherein this neurotransmitter system is implicated (ie, persistent pain, mood disorders, substance use disorders, etc). Here, we examined relationships between IL-1β, IL-1ra, and functional measures of the endogenous opioid system in 34 healthy volunteers, in the absence and presence of a standardized sustained muscular pain challenge, a psychophysical challenge with emotionally and physically stressful components.

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Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and reward responses in animal models. However, the role of the BDNF gene variants in responses to salient cues through DA neurotransmission in humans remains unexplored. Here, we studied the effect of the common functional BDNF Val(66)Met (rs6265) polymorphism on rewarding experiences in the striatum and DA-mediated responses to stress.

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Endogenous opioid and cannabinoid systems are thought to act synergistically regulating antinociceptive and reward mechanisms. To further understand the human implications of the interaction between these two systems, we investigated the role of the common, functional missense variant Pro129Thr of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, on psychophysical and neurotransmitter (dopaminergic, opioid) responses to pain and placebo-induced analgesia in humans. FAAH Pro129/Pro129 homozygotes, who constitute nearly half of the population, reported higher placebo analgesia and more positive affective states immediately and 24 h after placebo administration; no effects on pain report in the absence of placebo were observed.

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The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional μ-opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. We compared μ-opioid receptor availability in vivo at baseline, during pain expectation, and with moderate levels of sustained pain in 16 patients with chronic nonspecific back pain (CNBP) and in 16 age- and gender-matched healthy control subjects, using the μ-opioid receptor-selective radioligand [(11)C]carfentanil and positron emission tomography.

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Contemporary learning theories suggest that conditioning is heavily dependent on the processing of prediction errors, which signal a discrepancy between expected and observed outcomes. This line of research provides a framework through which classical theories of placebo effects, expectations and conditioning, can be reconciled. Brain regions related to prediction error processing [anterior cingulate cortex (ACC), orbitofrontal cortex or the nucleus accumbens] overlap with those involved in placebo effects.

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Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here, we assessed psychological traits in 50 healthy controls as to their capacity to predict placebo analgesic effects, placebo-induced activation of μ-opioid neurotransmission and changes in cortisol plasma levels during a sustained experimental pain challenge (hypertonic saline infused in the masseter muscle) with and without placebo administration. Statistical analyses showed that an aggregate of scores from Ego-Resiliency, NEO Altruism, NEO Straightforwardness (positive predictors) and NEO Angry Hostility (negative predictor) scales accounted for 25% of the variance in placebo analgesic responses.

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Article Synopsis
  • Neural systems are essential for survival by helping individuals respond to important stimuli in their environments, with genetic and metabolic factors influencing behavior and brain responses.
  • Research revealed a connection between variations in the leptin gene, plasma leptin levels, and dopamine release during stress, indicating that these genetic factors affect how the brain reacts to pain stress.
  • Leptin influences neuronal function, highlighting its potential role in conditions linked to dopamine, such as mood disorders, substance abuse, and obesity, revealing a link between metabolic processes and brain chemistry.
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Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT(2C)) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT(2C) receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT(2C) receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders.

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The endogenous opioid system is centrally involved in short-term placebo analgesic effects, but its potential regulation of memory and learning circuits, critical for the sustainability of placebo responses, has not been explored. Here we examined the recall of analgesic effects after placebo administration as a function of its initial capacity to activate μ-opioid neurotransmission. Memories of therapeutic/adverse responses 24 hours after placebo administration were associated with differences in μ-opioid neurotransmission in the Papez circuit, VTA, amygdala and septum.

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Dopamine (DA) neurotransmission through D2 receptors (DRD2) has been implicated in the regulation of reward processing, cognition and the effects of drugs of abuse, and also has significant effects in responses to stressors and salient aversive stimuli. An examination of the influence of genetic variation across multiple psychophysical measures therefore appears critical to understand the neurobiology of DA-modulated complex personality traits and psychiatric illnesses. To examine inter-individual variation in the function of DRD2 modulated mechanisms in healthy humans, we used a haplotype-based and single nucleotide polymorphism (SNP) investigation.

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