title: Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1.
abstract: BACKGROUND
  Neuroinflammation and nitroxidative stress are implicated in the pathophysiology of neuropathic pain. In view of both processes, microglial and astroglial activation in the spinal dorsal horn play a predominant role. The present study investigated the severity of neuropathic pain and the degree of glial activation in an inflammatory- and nitroxidative-prone animal model.
  
  
  METHODS
  Transgenic rats expressing mutated superoxide dismutase 1 (hSOD1 G93A) are classically used as a model for amyotrophic lateral sclerosis (ALS). Because of the associated inflammatory- and nitroxidative-prone properties, this model was used to study thermal and mechanical hypersensitivity following partial sciatic nerve ligation (PSNL). Next to pain hypersensitivity assessment, microglial and astroglial activation states were moreover characterized, as well as inflammatory marker gene expression and the glutamate clearance system.
  
  
  RESULTS
  PSNL induced thermal and mechanical hypersensitivity in both wild-type (WT) and transgenic rats. However, the degree of thermal hypersensitivity was found to be exacerbated in transgenic rats while mechanical hypersensitivity was only slightly and not significantly increased. Microglial Iba1 expression was found to be increased in the ipsilateral dorsal horn of the lumbar spinal cord after PSNL but such Iba1 up-regulation was enhanced in transgenic rats as compared WT rats, both at 3 days and at 21 days after injury. Moreover, mRNA levels of Nox2, a key enzyme in microglial activation, but also of pro-inflammatory markers (IL-1β and TLR4) were not modified in WT ligated rats at 21 days after PSNL as compared to WT sham group while transgenic ligated rats showed up-regulated gene expression of these 3 targets. On the other hand, the PSNL-induced increase in GFAP immunoreactivity spreading that was evidenced in WT rats was unexpectedly found to be attenuated in transgenic ligated rats. Finally, GLT-1 gene expression and uptake activity were shown to be similar between WT sham and WT ligated rats at 21 days after injury, while both parameters were significantly increased in the ipsilateral dorsal region of the lumbar spinal cord of hSOD1 G93A rats.
  
  
  CONCLUSIONS
  Taken together, our findings show that exacerbated microglial activation and subsequent inflammatory and nitroxidative processes are associated with the severity of neuropathic pain symptoms.
authors.affiliation: Group of Neuropharmacology, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Julie V
authors.initials: JV
authors.lastname: Berger
authors.forename: Ronald
authors.initials: R
authors.lastname: Deumens
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Goursaud
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schäfer
authors.forename: Patricia
authors.initials: P
authors.lastname: Lavand'homme
authors.forename: Elbert A
authors.initials: EA
authors.lastname: Joosten
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermans
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012584:Sciatic Nerve / Q000473:pathology / Q000601:surgery; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D027322:Amino Acid Transport System X-AG; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D018698:Glutamic Acid; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases