Effects of cold stimulation on secondary hyperalgesia (HA) induced by capsaicin in healthy volunteers

Little is known about the sensory characteristics and underlying mechanisms behind secondary hyperalgesia (HA) (2° HA). The aim of the present study was to investigate the relationships between two different noxious stimuli, mechanical and cold on capsaicin-induced 2° HA. Fourteen healthy volunteers were exposed to three different cold stimuli (20, 10, 0°C) 30 s each, on both forearms. The cold stimuli were applied before (baseline) and 8 min after intradermal administration of 50-μg capsaicin to the forearm, distally to the injection site in the inspected area of 2° HA. Pain intensities were assessed immediately after each cold stimulus by means of a visual analogue scale (cold-VAS). Additionally, areas of mechanical HA (cm²) were assessed distally and proximally to the injection site at three different time points: 5, 8 (right after the second series of cold stimuli), and 30 min after the injection. No significant differences in cold-VAS were found between pre- and post-capsaicin injection at the tested forearm (P = 0.334), whereas significant reduction from pre- to post-injection was found in cold-VAS in the control forearm (P = 0.024). Further, 8 min after the injection, the cold stimulation led to an expansion of 2° HA area (from 5.1 ± 1.38 to 11.4 ± 1.72 cm²) to punctuate stimuli distally but not proximally to the injection site (P < 0.05). It is concluded that there is no HA to cold stimuli within the area of mechanical 2° HA. However, cooling acts as a conditioning stimulus and expands the area of capsaicin-induced punctuate HA.