Intraplantar zymosan as a reliable, quantifiable model of thermal and mechanical hyperalgesia in the rat

Eur J Pain. 1997;1(1):43-52. doi: 10.1016/s1090-3801(97)90052-5.


The study of the mechanisms of thermal and mechanical hyperalgesia produced in human inflammatory conditions is dependent on a reliable, consistent model. The present investigation shows that the intraplantar administration of zymosan in the rat hindpaw produces a reliable and quantifiable thermal and mechanical hyperalgesia accompanied by oedema that closely mimics the symptoms of inflammation in man. Prior to the intraplantar injection of zymosan, there was no significant difference in withdrawal latencies, mechanical withdrawal thresholds or paw thickness between the left and right hindpaws. The intraplantar injection of zymosan (0.313-6.25 mg), an extract from yeast, produced a dose- and time-dependent thermal and mechanical hyperalgesia, a robust oedema and, at the greatest doses, produced evidence of spontaneous pain. At the least dose of zymosan tested (0.313 mg), there was a slight oedema; oedema was greatest at dosages > or =2.5 mg and was always maximal by 30 min postinjection, irrespective of the dose. On the other hand, thermal and mechanical hyperalgesia showed a more complex dose- and time-dependence. Mechanical hyperalgesia did not appear until dosages > or =1.25 mg and was maximal by 5 mg. In addition, mechanical hyperalgesia showed a time-dependent progressive onset so that hyperalgesia was maximal by the 4-h testing time-point. In contrast, thermal hyperalgesia showed a biphasic nature with two apparent maximal time-points (30 min and 4 h). There was an early-phase thermal hyperalgesia (maximal by 30 min) that was dose-dependent at dosages > or =2.5 mg (not apparent at lower dosages) and a late-phase (maximal by 4 h) that was dose-dependent at dosages > or =0.0625 mg. At the greatest doses administered (5 and 6.25 mg), there was evidence of spontaneous pain from the time of injection for up to 4 h that was characterized by occasional spontaneous flicking of the hindpaw, but more usually by holding the paw in an elevated position for extended periods of time. In addition, at the greatest dose tested (6.25 mg), all rats showed evidence of licking, biting and shaking of the injected hindpaw for up to 30-45 min after injection. These data demonstrate that the intraplantar injection of zymosan is a reliable and quantifiable model of tonic pain characterized by a dose- and time-dependent thermal and mechanical hyperalgesia accompanied by a robust oedema. This model is likely to be a useful, reliable model in which to study further the central and peripheral mechanisms of hyperalgesia.