title: Nefopam, a non-opioid analgesic, does not alleviate experimental work/effort dyspnoea in healthy humans: A randomised controlled trial.
abstract: Dyspnoea is a distressing and debilitating symptom with a major impact on quality of life. Alleviation of dyspnoea therefore constitutes a major clinical challenge. When causative physiological disorders cannot be corrected ("persistent dyspnoea"), nonspecific treatment must be considered. Morphine alleviates dyspnoea but has numerous side-effects including ventilatory depression, which justifies looking for alternatives. Certain forms of dyspnoea involve C-fibres, and can be attenuated by C-fibres blockade. We hypothesised that nefopam, a non-sedative benzoxazocine analgesic known to block the transient receptor potential vanilloid subtype 1 abundantly present on C-fibres, would attenuate dyspnoea.
  
  
  
  We conducted a randomised, double-blind, placebo-controlled crossover study of nefopam in healthy subjects submitted to experimental work/effort dyspnoea by inspiratory threshold loading (15 healthy male volunteers; age 23-41). We studied a perceptual outcome (dyspnoea visual analogue scale -D-VAS-) and a neurophysiological outcome (effect of nefopam on dyspnoea-pain counter-irritation as assessed by laser-evoked potentials; an effect of nefopam on dyspnoea was hypothetised to reduce the ability of dyspnoea to inhibit pain). Somaesthetic evoked potentials (SEPs) were studied as a control.
  
  
  
  A statistically significant decrease in LEP amplitude was observed in response to loading with nefopam (F = 19.1; p < 0.001) and placebo (F = 5.73 and p < 0.001), with no significant difference between nefopam and placebo and no change in SEP characteristics.
  
  
  
  In this study, nefopam did not exhibit any effects on dyspnoea.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Dangers
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale (Département "R3S"), F-75013, Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Laviolette
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Centre d'investigation Clinique Paris Est, Paris, France.
authors.forename: Bény
authors.initials: B
authors.lastname: Charbit
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale (Département "R3S"), F-75013, Paris, France. Electronic address: thomas.similowski@aphp.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Similowski
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale (Département "R3S"), F-75013, Paris, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Morélot-Panzini
mesh_terms: D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology; D005071:Evoked Potentials; D006801:Humans; D007320:Inspiratory Capacity / Q000502:physiology; D008297:Male; D009340:Nefopam / Q000494:pharmacology*; D011788:Quality of Life; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D009340:Nefopam
keywords: Analgesics; Counter-irritation; Dyspnoea; Laser-evoked potentials; Nefopam; Nefopam hydrochloride (PubChem CID: 155290); Pain