title: Redistribution of voltage-gated sodium channels after nerve decompression contributes to relieve neuropathic pain in chronic constriction injury.
abstract: Nerve decompression is an important therapeutic strategy to relieve neuropathic pain and promote the peripheral nerve regeneration. To address these issues, we investigated the effects of nerve decompression on relief of neuropathic pain behaviors, redistribution of voltage-gated sodium channels (VGSCs), and skin reinnervation with chronic constriction injury (CCI). At post-operative week (POW) 4, animals were divided into a decompression group, in which the ligatures were removed, and a CCI group, in which the ligatures remained. Thermal hyperalgesia and mechanical allodynia at POW 8 had distinct reductions in decompression group compared to CCI group. At that time in CCI group, morphological evidence of pan VGSCs (Pan Nav) and isoforms of VGSCs (Nav1.6, Nav1.9, except for Nav1.8) were shown the widely distribution along the injured sciatic nerve. All of the VGSCs in decompression group became clustering around the node of Ranvier, similar to the pattern of control sciatic nerve at POW 8. Skin reinnervation was demonstrated by epidermal nerve density (END) for protein gene product 9.5 (PGP 9.5)-immunoreactive (IR) nerve fibers and a significant difference between groups only at POW 24 (p=0.01). Growth-associated protein 43 (GAP-43) is participated in the nerve fiber growth and sprouting, a difference in END for GAP-43-IR nerve fibers at POW 24 between groups were also significant (p=0.02). These observations demonstrated that nerve decompression was accompanied with the disappearance of neuropathic pain behaviors after CCI. Morphological studies provided the evidence that redistribution of VGSCs along the injured sciatic nerve but still with an incomplete skin reinnervation. These significant findings demonstrated a role of VGSCs in the pathogenesis of neuropathic pain, and gave an approaching in pharmacological basis of therapeutics.
authors.affiliation: Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: To-Jung
authors.initials: TJ
authors.lastname: Tseng
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Hsieh
authors.affiliation: Department of Anatomy, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Miau-Hwa
authors.initials: MH
authors.lastname: Ko
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: sthsieh@ha.mc.ntu.edu.tw.
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D003250:Constriction; D019299:Decompression, Surgical; D004195:Disease Models, Animal; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007382:Intermediate Filaments / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D017288:Pain Threshold / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D012867:Skin / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D014110:Touch; D016896:Treatment Outcome; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Growth-associated protein 43; Nerve decompression; Neuropathic pain behaviors; Protein gene product 9.5; Skin innervations; Voltage-gated sodium channels