title: TGF-β1 attenuates spinal neuroinflammation and the excitatory amino acid system in rats with neuropathic pain.
abstract: Previous 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.
  
  
  CONCLUSIONS
  Clinically, 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.
authors.affiliation: 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.
authors.forename: Nan-Fu
authors.initials: NF
authors.lastname: Chen
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Chen
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Lu
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D018846:Excitatory Amino Acids; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha
keywords: Transforming growth factor-β1; chronic constriction injury; excitatory amino acids; glutamate transporters; tumor necrosis factor-α