title: Involvement of nerve injury and activation of peripheral glial cells in tetanic sciatic stimulation-induced persistent pain in rats.
abstract: Tetanic stimulation of the sciatic nerve (TSS) produces long-lasting pain hypersensitivity in rats. Long-term potentiation (LTP) of C- and A-fiber-evoked field potentials in the spinal cord has been explored as contributing to central sensitization in pain pathways. However, the peripheral mechanism underlying TSS-induced pain hypersensitivity remains largely unknown. We investigated the effect of TSS on peripheral nerve and the expression of activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) as a marker of neuronal injury. TSS induced a mechanical allodynia for at least 35 days and induced ATF3 expression in the ipsilateral DRG. ATF3 is colocalized with NF200-labeled myelinated DRG neurons or CGRP- and IB4-labeled unmyelinated ones. Furthermore, we found that TSS induced Wallerian degeneration of sciatic nerve at the level of myelinisation by S100 protein (to label Schwann cells) immunohistochemistry, luxol fast blue staining, and electron microscopy. TSS also elicited the activation of satellite glial cells (SGCs) and enhanced the colocalization of GFAP and P2X7 receptors. Repeated local treatment with tetrodotoxin decreased GFAP expression in SGCs and behavioral allodynia induced by TSS. Furthermore, reactive microglia and astrocytes were found in the spinal dorsal horn after TSS. These results suggest that TSS-induced nerve injury and glial activation in the DRG and spinal dorsal horn may be involved in cellular mechanisms underlying the development of persistent pain after TSS and that TSS-induced nerve injury may be used as a novel neuropathic pain model.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Liang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Lü
authors.forename: Jiale
authors.initials: J
authors.lastname: Yang
authors.forename: Yuqiu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins; D016253:Microscopy, Immunoelectron / Q000379:methods; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D037121:Plant Lectins / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000209:etiology* / Q000473:pathology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D051700:Activating Transcription Factor 3; C100745:Aif1 protein, rat; D000779:Anesthetics, Local; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C045475:Griffonia simplicifolia lectins; D008840:Microfilament Proteins; D016900:Neurofilament Proteins; D037121:Plant Lectins; D018048:Receptors, Purinergic P2; D009418:S100 Proteins; C408879:purinergic P2X8 receptor; C051774:neurofilament protein H; D013779:Tetrodotoxin