Effect of intrathecal injection of ifenprodil on the expression of 2B subunit mRNA of NMDA receptor in spinal cord in a mouse model of bone cancer pain

Abstract

Objective To investigate the effect of intrathecal injection of ifenprodil on the expression of 2B subunit mRNA of NMDA receptor (NR2B) in spinal cord in a mouse model of bone cancer pain. Methods One hundred and forty male C3H/HeJ mice weighing 20-25 g were randomly divided into 5 groups (n=28 each):group S sham operation; group B bone cancer pain; group I1- ifenprodil 2.5, 5 and 10 μg. Bone cancer pain was performed by intra-right-femur inoculations of osteolytic NCTC 2472 cells in group I1- and B. On the 14 d after inoculations, group I1-3 received intrathecal injection of ifenprodil 2.5, 5 and 10 μg dissolved in 5 μl solvent respectively, while group B and S received intrathecal injection of solvent. Seven mice was selected randomly from each group at 1 d before inoculations, at 1 h before, intrathecal injection of ifenprodil or solvent and at 2, 12 and 24 h after the injection (T1-5) tor determination of mechanical and thermal pain threshold. The mice were decapitated at T2.5 after determination of pain threshold and the L3-5 part of spinal cord was removed for determination of the expression of NR2B mRNA by RT-PCR. Results The mechanical and thermal pain threshold were significantly lower in group B and I1-3(P 0.05), and the expression of NR2B mRNA was significantly higher in group B and I3 while lower in group I2.3 than in group S (P 0.05). The mechanical and thermal pain threshold were significantly higher and the expression of NR2B mRNA was lower in group I3 than in group I2 (P <0.05). Conclusion lntratheeal injection of ifenprodil can attenuate bone cancer pain through blocking NR2B and inhibit hyperalgesia through down-regulating the NR2B mRNA expression in spinal cord. Key words: Piperidines; Receptors, N-methyl-D-aspartate; Spinal cord; Bone neoplasms; Injections, spinal