Nociceptive mechanisms modulate ozone-induced human lung function decrements.
We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535-1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18-59 yr) known to be "weak" (WR; n = 20) and "strong" O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0. 42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 microgram/kg iv) or saline. O3 exposure significantly (P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma beta-endorphin levels were not related to an individual's O3 responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3 responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.
Passannante
A N
AN
Department of Anesthesiology, School of Medicine, University of North Carolina at Chapel Hill, USA.
Hazucha
M J
MJ
Bromberg
P A
PA
Seal
E
E
Folinsbee
L
L
Koch
G
G
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D012129:Respiratory Function Tests; D013147:Spirometry; D017409:Sufentanil / Q000494:pharmacology; D001615:beta-Endorphin / Q000097:blood
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010083:Oxidants, Photochemical; D009270:Naloxone; D001615:beta-Endorphin; D010126:Ozone; D017409:Sufentanil