Repeated intradermal injection of low-dose carrageenan induces tachyphylaxis to evoked hyperalgesia

Changes in the thresholds to noxious mechanical and thermal stimulation were monitored in a group of normal sheep at different times (30 min-24 h) following intradermal injection of either low-dose (0.0625%) carrageenan, a widely used mucopolysaccharide irritant, or saline (0.9%) into the lateral aspect of the fore limb. Thresholds to noxious mechanical stimulation were measured on the ipsilateral limb whereas thresholds to noxious thermal stimulation were measured at a site distant to that of the injection, the ipsilateral ear. During the first 2 h after carrageenan injection the thresholds to noxious thermal stimulation fell, while thresholds to noxious mechanical stimulation were unaltered. The evoked hyperalgesia was reversed by the administration of non-steroidal anti-inflammatory agents. Hyperalgesia was not present 4 h after carrageenan injection in control or treated animals. This experiment was carried out on 3 further occasions and a diminishing response to injection of carrageenan was observed, suggesting development of tachyphylaxis to evoked thermal hyperalgesia.