UMLS:C0037315 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0037315 (sleep apnea)
8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The observation that the narcotic antagonist naloxone could inhibit analgesia produced by electrical stimulation of the brain indicated the involvement of an endogenous chemical in the relief of pain. Multiple endogenous opioid peptides have been identified that have similar pharmacological properties to known narcotic analgesics. The biosynthesis, release, and degradation of opioid peptides have been studied in order to better understand how the manipulation of endogenous opioid systems can be used to produce or augment analgesia. The results of our studies reveal that various conditions and manipulations, such as electrical brain stimulation, acupuncture, stress, and the administration of opioid analgesics, can cause the release of endogenous opioid peptides and possibly endogenous nonpeptide substances. It has also been discovered that nonopioid peptides, such as cholecystokinin, calcitonin, and angiotensin II, can alter the action of opioid analgesics by antagonizing or potentiating their effects. An understanding of the role of endogenous peptides in endogenous opioid mechanisms is necessary for the development of new ways to treat pain and such other disorders as sleep apnea in children (sudden infant death syndrome), head injury, and opioid addiction that involve the activation or alteration of endogenous opioid systems.
...
PMID:The role of endogenous peptides in the action of opioid analgesics. 352 91

Migraine and obesity are associated in several ways. First, both are prevalent and disabling disorders influenced by genetic and environmental risk factors. Second, migraine with aura, as obesity, seems to be a risk factor for cardiovascular events. Finally, large population-based studies suggest that obesity is a risk factor for chronic migraine after adjusting for comorbidities. In this article, we discuss plausible mechanisms that may account for this association. Several of the inflammatory mediators that are increased in obese individuals are important in migraine pathophysiology, including interleukins and calcitonin gene-related peptide (CGRP). These mediators may increase the frequency, severity, and duration of migraine attacks per se, which in turn would cause central sensitization. Repeated central sensitization may be associated with permanent neuronal damage close to the periaqueductal gray area, with poor modulation to pain. Obesity is also a state of sympathetic activation, which may contribute to increase in headache frequency. Furthermore, the levels of adiponectin are decreased in obesity. At low but not normal levels, adiponectin is nociceptive. Shared biologic predisposition may also play a major role. Orexins modulate both pain and metabolism. Dysfunction in the orexins pathways seems to be a risk factor for both conditions. Finally, conditions that are comorbid to both states (e.g., depression, sleep apnea) may also make the relationship between both diseases more complex.
...
PMID:Obesity, migraine, and chronic migraine: possible mechanisms of interaction. 1751 49

The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBel^CGRP neurons caused wakefulness, whereas optogenetic inhibition of PBel^CGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBel^CGRP terminals identified a network of forebrain sites under the control of a PBel^CGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea. VIDEO ABSTRACT.
...
PMID:A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia. 2910 5

We wanted to understand the brain circuitry that awakens the individual when there is elevated CO₂ or low O₂ (e.g., during sleep apnea or asphyxia). The sensory signals for high CO₂ and low O₂ all converge on the parabrachial nucleus (PB) of the pons, which contains neurons that project to the forebrain. So, we first deleted the vesicular glutamate transporter 2, necessary to load glutamate into synaptic vesicles, from neurons in the PB, and showed that this prevents awakening to high CO₂ or low O₂ We then showed that PB neurons that express calcitonin gene-related peptide (CGRP) show cFos staining during high CO₂ Using CGRP-Cre-ER mice, we expressed the inhibitory opsin archaerhodopsin just in the PB^CGRP neurons. Photoinhibition of the PB^CGRP neurons effectively prevented awakening to high CO₂, as did photoinhibition of their terminals in the basal forebrain, amygdala, and lateral hypothalamus. The PB^CGRP neurons are a key mediator of the wakening response to apnea.
...
PMID:Brain Circuitry for Arousal from Apnea. 3101 81