Pharmacological validation of early and late phase of rat mono‐iodoacetate model using the Tekscan system

Abstract

Previous pharmacological validations of the rat mono-iodoacetate (MIA)-induced chronic joint pain model were mostly performed by measuring weight-bearing (WB) deficit with an incapacitance tester. However, conventional incapacitance testers have several drawbacks including restrain stress on animal and sole use of hind limbs WB. The aim of the present study was to compare pharmacological sensitivity of the early (up to 1 week after MIA) versus late (between 2 and 4 weeks after MIA) phase of the rat MIA model using a highly sensitive tactile pressure measurement system (Tekscan(®)), which can measure weight borne by all four limbs and the tail in a non-restrained animal. The Tekscan(®) WB measurement system was used in MIA rats to examine the acute and chronic dosing effects of drugs that targeted different mechanisms. Electrophysiological recordings from joint afferents and biochemical analysis of synovial fluid were also performed. Dexamethasone, duloxetine and morphine significantly alleviated WB deficits in the Tekscan(®) system during both early and late phase of the MIA model while celecoxib and naproxen alleviated WB deficit only during the early phase. Similarly, naproxen was able to inhibit spontaneous neuronal activity from MIA joint afferents only during the early phase. Finally, concentrations of prostaglandin E(2) in synovial fluid were elevated only during the early phase of the rat MIA model. Our pharmacological validation studies using the Tekscan(®) system along with electrophysiological and biochemical results suggest different mechanisms for early and late phase of MIA-induced chronic joint pain in rat.