Fatigue, a commonly reported symptom, is defined as an overwhelming, debilitating, and sustained sense of exhaustion that decreases the ability to function and carry out daily activities. To date, cancer researchers have been in the forefront in investigating the possible biological mechanisms of fatigue, identifying inflammation, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and activation of the autonomic nervous system. The purpose of this systematic review is to describe fatigue and what is known about the biological mechanisms described in cancer in five chronic, noninfectious illnesses: heart failure, multiple sclerosis, chronic kidney disease, rheumatoid arthritis, and chronic obstructive pulmonary disease. We searched PubMed and EMBASE using fatigue as a major Medical subject headings (MeSH) heading with each individual disease added as a search term followed by each biological mechanism. We included only primary research articles published in English between 1996 and 2016 describing studies conducted in adult humans. We identified 26 relevant articles. While there is some evidence that the biological mechanisms causing fatigue in cancer are also associated with fatigue in other chronic illnesses, more research is needed to explore inflammation, the HPA axis, and the autonomic nervous system, and other mechanisms in relation to fatigue in a variety of chronic illnesses.

Context. Fatigue is a symptom reported by patients with a variety of chronic conditions. However, it is unclear whether fatigue is similar across conditions. Better understanding its nature could provide important clues regarding the mechanisms underlying fatigue and aid in developing more effective therapeutic interventions to decrease fatigue and improve quality of life. Objectives. To better understand the nature of fatigue, we performed a qualitative metasynthesis exploring patients' experiences of fatigue across five chronic noninfectious conditions: heart failure, multiple sclerosis, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease. Methods. We identified 34 qualitative studies written in the last 10 years describing fatigue in patients with one of the aforementioned conditions using three databases (Embase, PubMed, and CINAHL). Studies with patient quotes describing fatigue were synthesized, integrated, and interpreted. Results. Across conditions, patients consistently described fatigue as persistent overwhelming tiredness, severe lack of energy, and physical weakness that worsened over time. Four common themes emerged: running out of batteries, a bad life, associated symptoms (e.g., sleep disturbance, impaired cognition, and depression), and feeling misunderstood by others, with a fear of not being believed or being perceived negatively. Conclusion. In adults with heart failure, multiple sclerosis, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease, we found that fatigue was characterized by severe energy depletion, which had negative impacts on patients' lives and caused associated symptoms that exacerbated fatigue. Yet, fatigue is commonly misunderstood and inadequately acknowledged.

Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste–pain sensorial experiences are not fully understood. This article provides a narrative review of literature examining the role of TRP channels on taste and pain perception. Genomic variability in the TRPV1 gene has been associated with alterations in various pain conditions. Moreover, polymorphisms of the TRPV1 gene have been associated with alterations in salty taste sensitivity and salt preference. Studies of genetic variations in TRP genes or modulation of TRP pathways may increase our understanding of the shared biological mediators of pain and taste, leading to therapeutic interventions to treat many diseases.

Neuropeptides, a diverse class of signaling molecules in the nervous system, modulate various biological effects including membrane excitability, synaptic transmission and synaptogenesis, gene expression, and glial cell architecture and function. To date, most of what is known about neuropeptide action is limited to subcortical brain structures and tissue outside of the central nervous system. Thus, there is a knowledge gap in our understanding of neuropeptide function within cortical circuits. In this review, we provide a comprehensive overview of various families of neuropeptides and their cognate receptors that are expressed in the prefrontal cortex (PFC). Specifically, we highlight dynorphin, enkephalin, corticotropin-releasing factor, cholecystokinin, somatostatin, neuropeptide Y, and vasoactive intestinal peptide. Further, we review the implication of neuropeptide signaling in prefrontal cortical circuit function and use as potential therapeutic targets. Together, this review summarizes established knowledge and highlights unknowns of neuropeptide modulation of neural function underlying various biological effects while offering insights for future research. An increased emphasis in this area of study is necessary to elucidate basic principles of the diverse signaling molecules used in cortical circuits beyond fast excitatory and inhibitory transmitters as well as consider components of neuropeptide action in the PFC as a potential therapeutic target for neurological disorders. Therefore, this review not only sheds light on the importance of cortical neuropeptide studies, but also provides a comprehensive overview of neuropeptide action in the PFC to serve as a roadmap for future studies in this field.