Nonviral vector plasmid DNA encoding human proenkephalin gene attenuates inflammatory and neuropathic pain-related behaviors in mice

• Published in: Neuroscience letters Vol. 634; pp. 87 - 93
• Main Authors: Hu, Chunsheng, Cai, Zhenzhen, Lu, Yuxin, Cheng, Xiaochen, Guo, Qi, Wu, Zuze, Zhang, Qinglin
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 10.11.2016
• Subjects: Adjuvants, Immunologic; Animals; Behavior, Animal; DNA - administration & dosage; Enkephalins - genetics; Enkephalins - metabolism; Freund's Adjuvant; Gene transfer; Genetic Therapy; Genetic Vectors; Humans; Hyperalgesia - physiopathology; Hyperalgesia - therapy; Inflammation - genetics; Inflammation - immunology; Inflammation - physiopathology; Inflammation - therapy; Injections, Intramuscular; Injections, Spinal; Neuralgia - genetics; Neuralgia - physiopathology; Neuralgia - therapy; Pain - genetics; Pain - immunology; Pain - physiopathology; Pain behavior; Pain Management; Plasmid; Plasmids; Proenkephalin; Protein Precursors - genetics; Protein Precursors - metabolism; Sciatic Nerve - injuries; Plasmid; Proenkephalin; Gene transfer; Pain behavior
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.09.040

•Peripheral or spinal delivery of pVAX1-PENK alleviates CFA-induced pain for an extended period.•Peripheral or spinal delivery of pVAX1-PENK attenuates SNI-induced nocifensive behaviors in mice.•The analgesic effect of pVAX1-PENK is blocked by naloxone hydrochloride. Inflammatory pain and neuropathic pain are major clinical health issues that represent considerable social and economic burden worldwide. In the present study, we investigated the anti-nociceptive efficacy of delivery of human proenkephalin gene by a plasmid DNA vector (pVAX1-PENK) on complete Freund’s adjuvant (CFA) induced inflammatory pain and spared nerve injury (SNI) induced neuropathic pain in mice. Mice were intramuscularly or intrathecally administered pVAX1 or pVAX1-PENK, respectively. Pain thresholds in the pVAX1-PENK treated mice were significantly higher at day 3, then reached a peak at day 7 and lasted 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 indicate that peripheral or spinal delivery of a plasmid encoding human proenkephalin gene provides a potential therapeutic strategy for inflammatory pain and neuropathic pain.