title: Variability in C-type lectin receptors regulates neuropathic pain-like behavior after peripheral nerve injury.
abstract: BACKGROUND
  Neuropathic pain is believed to be influenced in part by inflammatory processes. In this study we examined the effect of variability in the C-type lectin gene cluster (Aplec) on the development of neuropathic pain-like behavior after ligation of the L5 spinal nerve in the inbred DA and the congenic Aplec strains, which carries seven C-type lectin genes originating from the PVG strain.
  
  
  RESULTS
  While both strains displayed neuropathic pain behavior early after injury, the Aplec strain remained sensitive throughout the whole study period. Analyses of several mRNA transcripts revealed that the expression of Interleukin-1β, Substance P and Cathepsin S were more up-regulated in the dorsal part of the spinal cord of Aplec rats compared to DA, indicating a stronger inflammatory response. This notion was supported by flow cytometric analysis revealing increased infiltration of activated macrophages into the spinal cord. In addition, macrophages from the Aplec strain stimulated in vitro displayed higher expression of inflammatory cytokines compared to DA cells. Finally, we bred a recombinant congenic strain (R11R6) comprising only four of the seven Aplec genes, which displayed similar clinical and immune phenotypes as the Aplec strain.
  
  
  CONCLUSIONS
  We here for the first time demonstrate that C-type lectins, a family of innate immune receptors with largely unknown functions in the nervous system, are involved in regulation of inflammation and development of neuropathic pain behavior after nerve injury. Further experimental and clinical studies are needed to dissect the underlying mechanisms more in detail as well as any possible relevance for human conditions.
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, CMM L8:05, Karolinska Institutet, Stockholm, Sweden. Cecilia.Dominguez@ki.se.
authors.forename: Cecilia A
authors.initials: CA
authors.lastname: Dominguez
authors.forename: Karl E
authors.initials: KE
authors.lastname: Carlström
authors.forename: Xing-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Faiez
authors.initials: F
authors.lastname: Al Nimer
authors.forename: Rickard P F
authors.initials: RP
authors.lastname: Lindblom
authors.forename: Andre
authors.initials: A
authors.lastname: Ortlieb Guerreiro-Cacais
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D014644:Genetic Variation; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D005810:Multigene Family; D009437:Neuralgia / Q000378:metabolism* / Q000628:therapy; D009479:Neuropeptides / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D015398:Signal Transduction; D013373:Substance P / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D037181:Lectins, C-Type; D009479:Neuropeptides; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D013373:Substance P; D002403:Cathepsins; C028217:cathepsin S