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

Abstract

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.

NADPH Oxidase-4 Maintains Neuropathic Pain after Peripheral Nerve Injury

“…Fifteen microliters of a zymosan A suspension (5 mg/ml in 0.1 M PBS, pH 7.4; Sigma-Aldrich) or 20 l of complete Freund's adjuvant (CFA; containing 1 mg/ml heat-killed Mycobacterium tuberculosis in 85% paraffin oil and 15% mannide monooleate; Sigma-Aldrich) was injected into the plantar subcutaneous space of a hindpaw (Meller and Gebhart, 1997).…”

The Protein Kinase IKKε Is a Potential Target for the Treatment of Inflammatory Hyperalgesia

“…Pawwithdrawal latency was assessed using a Dynamic Plantar Aesthesiometer, as described above. After baseline measurements, hind paw inflammation was induced by s.c. injection of 20 ml a 10 mg/ml zymosan A (Sigma-Aldrich, Munich, Germany) suspension in PBS (0.1 M [pH 7.4]) into the mid-plantar region of the left hind paw (21). The mean of four consecutive trials, with 10-s intervals, was determined hourly up to 8 h, as well as at 24 and 48 h after zymosan injection.…”

Cysteine-Rich Protein 2, a Novel Downstream Effector of cGMP/cGMP-Dependent Protein Kinase I-Mediated Persistent Inflammatory Pain

“…We then tested the extent of mechanical hyperalgesia evoked by injection of zymosan or CFA into a hindpaw (Meller and Gebhart, 1997;Ferreira et al, 2001). Under baseline conditions, CRP2…”