Independent effects of ischaemia and noradrenaline on thermal hyperalgesia in capsaicin-treated skin

Noradrenaline increases thermal hyperalgesia in skin previously sensitized by capsaicin. The aim of the present study was to determine whether a vasoconstrictor ischaemic effect of noradrenaline increases thermal hyperalgesia. Heat pain thresholds were measured in the capsaicin-treated and untreated skin on the forearms of 13 normal volunteers. The iontophoresis of noradrenaline induced thermal hyperalgesia in untreated skin (mean heat pain threshold at the noradrenaline site 42.2 +/- 4.2 degrees C compared with 47.3 +/- 3.5 degrees C at control sites, P < 0.001), and increased thermal hyperalgesia in capsaicin-treated skin (mean heat pain threshold at the noradrenaline site 38.6 +/- 2.1 degrees C compared with 45.7 +/- 5.6 degrees C at control sites, P < 0.001). Heat pain thresholds did not change during venous congestion, induced by applying a cuff pressure of 60 mmHg to the upper arm. Increasing the cuff pressure to 200 mmHg decreased the heat pain threshold by 2.4 +/- 2.3 degrees C at control sites in the capsaicin-treated skin (P < 0.01); nevertheless, thermal hyperalgesia was greater at the noradrenaline site than at control sites during arterial occlusion, both in capsaicin-treated and untreated skin (in the capsaicin-treated skin, mean heat pain threshold during arterial occlusion 38.1 +/- 3.3 degrees C at the noradrenaline site compared with 43.4 +/- 6.5 degrees C at control sites, P < 0.001; in the untreated skin, mean heat pain threshold at the noradrenaline site 44.3 +/- 3.6 degrees C compared with 47.9 +/- 3.1 degrees C at control sites, P < 0.001). Thermal hyperalgesia subsided in control sites in the capsaicin-treated skin after cuff pressure was released, but persisted at sites of noradrenaline iontophoresis (in the capsaicin-treated skin, mean heat pain threshold during reactive hyperaemia 45.2 +/- 5.1 degrees C at the noradrenaline site compared with 49.3 +/- 6.0 degrees C at control sites, P < 0.01; in the untreated skin, mean heat pain threshold at the noradrenaline site 46.5 +/- 3.3 degrees C compared with 48.8 +/- 3.0 degrees C at control sites, P < 0.001). Arterial occlusion could increase thermal hyperalgesia in capsaicin-treated skin by preventing the dispersal of nociceptive substances peripherally or through central summation of nociceptive signals. The hyperalgesic effect of noradrenaline is greater than the hyperalgesic effect of ischaemia, suggesting that some mechanism in addition to vasoconstriction contributes to the nociceptive effect of noradrenaline.