pVAX1 vector

Inflammatory and neuropathic pain are major clinical health problems that cause considerable social and economic burden worldwide. In this study, researchers investigated the effects of delivery of the human proenkephalin gene via a plasmid DNA vector (pVAX1-PENK) on complete Freund's adjuvant (CFA)-induced inflammatory pain and protection from neurological injury (SNI) in mice. Antinociceptive efficacy in induced neuropathic pain. Mice were administered pVAX1 or pVAX1-PENK intramuscularly or intrathecally, respectively. The pain threshold of pVAX1-PENK-treated mice was significantly elevated on day 3, then peaked on day 7 and continued until day 28 after gene transfer, and the analgesic effect of pVAX1-PENK was blocked with naloxone hydrochloride. In contrast, pVAX1-treated mice did not significantly improve pain thresholds. These results suggest that peripheral or spinal delivery of a plasmid encoding the human proenkephalin gene provides a potential therapeutic strategy for inflammatory and neuropathic pain.

After plasmid injection, Leu-ENK expression was measured in muscle or spinal cord tissue. As shown in Figure 1, Leu-ENK levels in muscle or spinal cord of the mice were lower in the naïve, i.m. pVAX1 and i.t. pVAX1 groups than in the i.m. or i.t. pVAX1-PENK group. In pVAX1-PENK-treated CFA mice, Leu-ENK increased from day 3 to day 28 and peaked at day 7 (Figure 1A). Consistently, in pVAX1-PENK-treated SNI mice, Leu-ENK expression levels peaked at day 7 and then gradually declined (Figure 1B).

Figure 1. Enkephalin expression analysis. Following intramuscular or intrathecal injection of pVAX1-PENK in CFA mice (A) and SNI mice (B), Leu-ENK content was determined in the injection site muscle or L3-5 spinal cord. (Hu C, et al. 2016)