Novel, small molecule induced GABA-hATSCs for targeting of neuropathic pain.

Abstract

Recent study showed that ROS has a crucial function during neuropathic pain development and maintenance. In this study, we suggest that a small, novel molecule, CMB-1078, can effectively induce GABAergic neuronal differentiation from human adipose tissue-derived stromal cells (hATSCs; GABA-hATSCs), which play a key role in ameliorating neuropathic pain caused by spinal cord injury. Compared to control hATSCs, the engraftment of GABA-hATSCs into animals with neuropathic pain significantly reduced secondary injury, including inflammation, GABAergic neuronal degeneration, and the circulation or propagation of proinflammatory factors cyclooxygenase2 (COX2), interlukin-1 β (IL-1β), NADPH oxidase 2 (NOX 2), NADPH oxidase 4 (NOX 4) and tumor necrosis factor α (TNFα) into the lesion. At the protein level, we also demonstrated that GABA-hATSCs engrafted into animals with neuropathic pain increased glutamic acid decarboxylase 65 (GAD65) and glutamic acid decarboxylase 67 (GAD67) expression levels. In addition, we evaluated functional pain behavior in the GABA-hATSCs- or control hATSCs-engrafted animal group, the pain in the PBS-infused animal group, and healthy animals by measuring mechanical and heat sensitivity. The pain plus GABA-hATSCs-engrafted animal groups showed paw withdrawal thresholds (PWTs) that gradually improved. In contrast, the mice with neuropathic pain did not show improved PWT. Further, the control hATSCs-engrafted animal showed attenuated PWTs. Finally, we suggest that the molecular function of GABA-hATSCs in neuropathic pain may provide potential therapeutic tools for the treatment of pain by controlling the pathology of neuropathic pain through neuroprotection and regeneration.

• Authors: Min Jee, Young Im, Jee I N Choi, Soo Kyung Kang
• Journal: Human gene therapy (Hum Gene Ther) (Mar 09 2013) ISSN: 1557-7422 [Electronic] United States
• PMID: 23473301 (Publication Type: Journal Article, Retracted Publication)