Modulating cAMP responsive element binding protein 1 attenuates functional and behavioural deficits in rat model of neuropathic pain.

Abstract

Chronic neuropathic pain (NP) has become a worldwide public health problem. This study was aimed to establish graded NP model to investigate the effect of CREB1 on nerve repair and NP after peripheral nerve injury. Based on NP model, we measured the 50% paw withdrawal threshold (PWT) of rat hind paws and sciatic functional index (SFI). Luxol fast blue staining was performed to measure the ratio of distal myelin sheath to proximal (DPR). The c-Fos, GFAP, CX3CR1 and IBA-1 expressions in spinal cord were measured by Western blot. The expression levels of CREB1 and ATF-3 in dorsal root ganglion (DRG) were both measured. Intrathecal injection was performed by using recombinant CREB, or anti-CREB antibody for NP model, respectively. The above indexes were detected. In NP model, the 50% PWTs and DPR were gradually reduced and SFI was increased. The c-Fos, GFAP, CX3CR1 and IBA-1 expressions were increased compared to control group. The CREB1 and ATF-3 expressions in DRG showed gradually increase. With the injection of recombinant CREB, the similar changes were found in rats compared with NP model. While after anti-CREB1 antibody injection, all effects of CREB1 were impaired. Likewise, anti-CREB1 antibody treatment increased 50% PWT and DPR, decreased SFI, decreased expressions of c-Fos, GFAP, CX3CR1 and IBA-1. Besides, ATF-3 expression was inhibited by CREB1 suppression. CREB1 involved in the regulation of NP and nerve repair process, suggesting that CREB1 has potential as a new target for the treatment of chronic NP.