Comparison of three models of neuropathic pain in mice using a new method to assess cold allodynia: The double plate technique

Abstract

The recent identification of receptors sensitive to cold stimuli increased the significance of using mice to study cold allodynia, one of the important features of neuropathic pain. However, commonly used techniques (simple cold plate and acetone technique) may be inappropriate to study cold allodynia in mice because of problems of interpretation. We have developed a new method for assessing aversion to a cold non-noxious stimulus. It consists of calculating the time that mice spend on a non-noxious cold plate during their explorative behavior versus a thermoneutral one. We used three different models of neuropathic pain: chronic constriction injury of the sciatic nerve (CCI), partial sciatic nerve ligation (PSL) and chronic constriction of the saphenous nerve (CCS) with their respective sham groups and naive animals to assess the double plate in comparison to the acetone drop technique. All operated mice displayed cold allodynia with both methods. The response to acetone and the time spent on the cold plate were correlated ( r = −0.93) and we also showed that the CCI mice were more sensitive to cold. Pharmacological validation of this technique showed that CCI induced cold allodynia was alleviated by gabapentin. In conclusion, the double plate technique provides a new, relevant method for assessing cold allodynia in mice. The advantages and drawbacks with the other techniques are discussed.