NOCICEPTIVE MECHANISMS MODULATE OZONE-INDUCED HUMAN LUNG-FUNCTION DECREMENTS

We have previously suggested that ozone (O-3)-induced pain-related sym ptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P.A. Bromberg. J. App l. Physiol. 67: 1535-1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reve rse O-3-induced symptomatic and lung functional responses. The objecti ves of this study were to determine whether O-3-induced pain limits ma ximal inspiration and whether endogenous opioids contribute to modulat ion of the effects of inhaled O-3 On lung function. The participants i n this double-blind crossover study were healthy volunteers (18-59 yr) known to be ''weak'' (WR; n = 20) and ''strong'' O-3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exp osures to 0.42 parts/million O-3 with moderate intermittent exercise. Immediately after post-O-3 spirometry, the WR were randomly given eith er naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received ei ther sufentanil (0.2 mu g/kg iv) or saline. O-3 exposure significantly (P < 0.001) impaired lung function. In SR, sufentanil rapidly, althou gh not completely, reversed both the chest pain and spirometric effect s (forced expiratory volume in 1 s; P ( 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no sig nificant effect on WR. Plasma beta-endorphin levels were not related t o an individual's O-3 responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O-3 responsiveness. These obser vations demonstrate that nociceptive mechanisms play a key role in mod ulating O-3-induced inhibition of inspiration but not in causing lack of spirometric response to O-3 exposure in WR.