Effect of postsynaptic density-95 peptide vaccine on brain-derived neurotrophic factor mRNA expression of spinal cord in neuropathic pain rats

Abstract

Objective To investigate the effect of postsynaptic density (PSD)-95 peptide vaccine on neuropathic pain (NP) in rats.Methods Adult female SD rats were selected to produce retained nerve injury (SNI) model.Seven days after successful SNI surgery,24 rats were randomly divided into 4 groups (n =6)..NP group,PBS group,keyhole limpet hemocyanin (KLH) group and PSD-95 group.Rats in PSD-95 group were given multi-point injection of PSD-95 peptide vaccine on the back subcutaneously,on both sides 3 times at 2 weeks interval,and those in PBS and KLH groups were given PBS or KLH.The mechanical pain threshold was determined one day before the preparation of SNI (underlying value),1 day before the first immunization,7 days and 14 days after the third immunization (T0-3).Rats were killed at T3 to determine the mRNA expression of brain-derived neurotrophic factor (BDNF) in the spinal cord lumbar enlargement.Results Compared with T0,the mechanical pain threshold of each group at T1 was decreased (13.2±1.1 vs.1.9±0.5; 12.9±0.9 vs.1.9±0.7; 13.5±1.0vs.1.8±0.5; 13.1±1.1 vs.1.7 ± 0.6),and that in NP group,PBS group and KLH group at T2 and T3 was decreased (2.4 ± 0.6,2.5 ± 0.6 ; 3.2 ± 0.9,3.4 ± 0.8 ; 3.3 ± 0.8,3.5 ± 1.1) (P ＜ 0.05).Compared with T1,the mechanical pain threshold in PSD-95 group at T2 and T3 was increased (1.7 ±0.6 vs.10.5 ±2.1,11.2 ± 1.9),and the mRNA expression of BDNF was down-regulated (1.48 ± 0.21 vs.0.92 ± 0.13,0.88 ± 0.12) (P ＜ 0.05).As compared with NP group,the mechanical pain threshold in PSD-95 group was increased (2.4 ±0.6 vs.10.5 ±2.1 ; 2.5 ±0.6 vs.11.2 ± 1.9),and the mRNA expression of BDNF was downregulated (1.48±0.17 vs.0.92±0.13; 1.52±0.23 vs.0.88±0.12) (P＜0.05).There was no significant difference in various indicators between PBS group and KLH group (P ＞ 0.05).Conclusion PSD-95 peptide vaccine has analgesic effects on neuropathic pain in rats,which may be related to the downregulation of the mRNA expression of spinal BDNF. Key words: Vaccines ; Postsynaptic density-95 ; Brain-derived neurotrophic factor; Neuropathic pain