Is the Second Phase of the Formalin Test Useful to Predict Activity in Chronic Constriction Injury Models? A Pharmacological Comparison in Different Species

Abstract

This study presents data of several reference drugs in rats and gerbils for both the second phase of the formalin test and the cold allodynia in animals with a constriction injury of the sciatic nerve. A pharmacological validation of the formalin test and the CCI model in gerbils was performed. It was evaluated whether the second phase of the formalin test could be used as a pharmacological screening to predict outcome in the cold plate test in CCI animals. Male Sprague Dawley and Wistar rats and male gerbils were used for both tests. For the formalin test, animals were injected in the right hind paw (5% formalin rat: 0.05 microl; gerbil: 0.01 microl) and flinching and licking or biting were recorded. For CCI testing, a Bennett operation was performed on the left hind paw 7 days before testing. Cold plate allodynia was evaluated before and after drug treatment. In rats, a good correlation between both test conditions for morphine, fentanyl, MK-801 and flunarizine was found. Clonidine tends to have more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate demonstrate to be more active in the cold plate. In gerbils, a good correlation between both test conditions for fentanyl and ketoprofen was found. Tramadol and CP-96345 tend to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrates to be more active in the cold plate test. In the present acute test conditions, there is a correlation in the pharmacological activity in rats and gerbils for the tested compounds a correlation between the second phase of the formalin test and the cold allodynia in CCI animals is found. Comparing to human data the screening drugs tested in this study show a correlation between animal and human studies in these specific circumstances. Further validation studies are needed to make these correlations clinical applicable.