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Pain and dyspnea frequently coexist in many clinical situations. However, whether the two different symptoms interact with each other has not been elucidated. To elucidate the interaction between pain and dyspneic sensations, the authors investigated separately the effects of pain on dyspnea and the effects of dyspnea on pain in 15 healthy subjects.Subjects were asked to rate their sensation of pain or dyspnea using a visual analog scale (VAS) during pain stimulation produced by tourniquet inflation (inflation cuff pressure: 350 mmHg) around the calf, and/or the respiratory loading consisted of a combination of resistive load (77 cm H2O · l−1 · s−1) and hypercapnia induced by extra mechanical dead space (255 ml). In addition to changes in VAS scores, changes in ventilatory airflow and airway pressure were continuously measured.Pain stimulation and loaded breathing increased VAS scores, ventilation, and occlusion pressure (P0.1). The addition of a pain stimulus during loaded breathing increased the dyspneic VAS score (median 56 [interquartile range 50–62]vs.64 [55–77]: beforevs.after addition of pain stimulus,P< 0.05) with concomitant increases in minute ventilation (10.8 [10.1–13.3]vs.12.4 [11.0–14.8] l/min,P< 0.05) and P0.1 (5.5 [4.9–7.2]vs.6.8 [5.8–9.0] cm H2O,P< 0.05). The addition of respiratory loading during pain stimulation did not cause a significant change in pain VAS score (40 [33–55]vs.31 [30–44]: beforevs.after addition of respiratory loading), although both additional burdens increased further minute ventilation (10.0 [8.8–10.9]vs.12.0 [10.6–13.2] l/min,P< 0.05) and P0.1 (2.5 [2.0–3.0]vs.6.2 [4.9–7.0] cm H2O,P< 0.05).The authors’ findings suggest that pain intensifies the dyspneic sensation, presumably by increasing the respiratory drive, whereas dyspnea may not intensify the pain sensation.