The Role of NMDA and non-NMDA Receptors for cFos Protein Expression on the Spinal Cord in Formalin Pain Model

Shim, Dae Moo; Song, Ha Heon; Kim, Tae Gyun; Cha, Sang Hoon

Abstract

The purpose of this study was to evaluate effect of NMDA and non-NMDA receptor antagonists on pain-related behavioral change and cFos-like protein expression on the spinal dorsal horn neurons following subcutaneous injection of diluted formalin into one paw. Depending on the drug pretreatment paradigm, animals were divided into four groups; the saline treated, the MK801 treated, CNQX treated, and both MK801 and CNQX treated. Each group was consisted of fifteen rats. After single injection of formalin, all animals exhibited signs of phasic pain(first pain) within 15 minutes, which was followed by a long lasting tonic pain(second pain), thereafter. MK801 pretreatment significantly reduced only the tonic pain. On the other hand, the intrathecal administration of CNQX significantly inhibited only the first phasic pain behavior. An injection of formalin into one hindpaw elicited cFos-like protein expression on the ipsilateral dorsal horn neurons from T12 to S1 spinal cord. The cFos-like protein expression was especially strong in the L3-5 segments and sustained more than 8 hours after the formalin injection. The cFos-like protein expression was peaked two after the formalin injection in superficial layer (laminar III-VII). The MK801 pretreatment reduced the number of cFos-like protein positive neurons significantly one hour after the formalin injection in the superficial dorsal horn. The reduction was observed in the superficial as well as deep layers four hours after the injection. The pretreatment of MK801+CNQX reduced significantly cFos-like protein expression on the both superficial and deep layers of the ipsilateral dorsal horn throughout the experimental session. However, CNQX application did not produce any significant reduction of cFos-like protein expression on the dorsal horn neurons. These results suggest that NMDA receptor may play an more important role in cFos-like protein expression of ipsilateral dorsal horn neurons on the formalin evoked pain model of the rat.