• Nan-Fu Chen, Shi-Ying Huang, Wu-Fu Chen, Chun-Hong Chen, Ching-Hsiang Lu, Chun-Lin Chen, San-Nan Yang, Hui-Min Wang, and Zhi-Hong Wen.
• Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan; Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
• J Pain. 2013 Dec 1; 14 (12): 1671-85.

UnlabelledPrevious studies have reported that the intrathecal (i.t.) administration of transforming growth factor β1 (TGF-β1) prevents and reverses neuropathic pain. However, only limited information is available regarding the possible role and effects of spinal TGF-β1 in neuropathic pain. We aimed to investigate the antinociceptive effects of exogenous TGF-β1 on chronic constriction injury (CCI)-induced neuropathic pain in rats. We demonstrated that sciatic nerve injury caused a downregulation of endogenous TGF-β1 levels on the ipsilateral side of the lumbar spinal dorsal gray matter, and that the i.t. administration of TGF-β1 (.01-10 ng) significantly attenuated CCI-induced thermal hyperalgesia in neuropathic rats. TGF-β1 significantly inhibited CCI-induced spinal neuroinflammation, microglial and astrocytic activation, and upregulation of tumor necrosis factor-α. Moreover, i.t. TGF-β1 significantly attenuated the CCI-induced downregulation of glutamate transporter 1, the glutamate aspartate transporter, and the excitatory amino acid carrier 1 on the ipsilateral side. Furthermore, i.t. TGF-β1 significantly decreased the concentrations of 2 excitatory amino acids, aspartate and glutamate, in the spinal dialysates in CCI rats. In summary, we conclude that the mechanisms of the antinociceptive effects of i.t. TGF-β1 in neuropathy may include attenuation of spinal neuroinflammation, attenuation, or upregulation of glutamate transporter downregulation, and a decrease of spinal extracellular excitatory amino acids.PerspectiveClinically, medical treatment is usually initiated after the onset of intractable pain. Therefore, in the present study, i.t. TGF-β1 was designed to be administered 2 weeks after the establishment of CCI pain. Compared to the continuous TGF-β1 infusion mode, single-dose administration seems more convenient and practical to use.Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

40 keywords...

hide…