title: Understanding mechanisms and documenting plausibility of palliative interventions for dyspnea.
abstract: OBJECTIVE
  To review the mechanisms for the perception of dyspnea and to consider the plausibility of interventions that palliate dyspnea after optimal treatment of the underlying disease.
  
  
  RESULTS
  Activation of sensory receptors by blood gas abnormalities, mechanical respiratory loads, and hyperinflation provides afferent information to the central nervous system for integration and processing. It has been proposed that a discriminative pathway processes afferent impulses to the somatosensory cortex that reflects the intensity of dyspnea, whereas an affective pathway projects afferent impulses to structures of the limbic system that reflects the unpleasantness of dyspnea. In one study, patients with chronic obstructive pulmonary disease reported consistently higher ratings of breathlessness after administration of naloxone, an opioid receptor antagonist, compared with physiological saline during high-intensity treadmill exercise. This finding supports the role of endogenous opioids in modulating dyspnea. Nebulized furosemide, anti-inflammatory therapy, and chest wall vibration are potential approaches for modulating lung and chest wall receptors to relieve dyspnea.
  
  
  CONCLUSIONS
  Targets for palliating dyspnea in patients with advanced disease include sensory receptors within the lung/chest wall and the central nervous system. The opioid system plays an important role in palliating dyspnea. Both endogenous (β-endorphins) and exogenous (morphine) opioids modulate breathlessness.
authors: Dartmouth Medical School, Hanover, NH, USA, USA. Donald.a.mahler@hitchcock.org
authors: Donald A
authors: DA
authors: Mahler
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology; D004417:Dyspnea / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D004525:Efferent Pathways / Q000187:drug effects / Q000503:physiopathology; D004723:Endorphins / Q000502:physiology*; D006801:Humans; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000502:physiology; D010166:Palliative Care; D016584:Panic Disorder / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology
chemical_list: D004723:Endorphins; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D009270:Naloxone