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@ARTICLE{Vogel:282360,
      author       = {A. Vogel and T. Ueberbach and A. Wilken-Schmitz and L.
                      Hahnefeld and L. Franck and M.-P. Weyer and T. Jungenitz and
                      T. Schmid$^*$ and G. Buchmann and F. Freudenberg and R. P.
                      Brandes and R. Gurke and S. W. Schwarzacher and G.
                      Geisslinger and T. Mittmann and I. Tegeder},
      title        = {{R}epetitive and compulsive behavior after
                      {E}arly-{L}ife-{P}ain associated with reduced long-chain
                      sphingolipid species.},
      journal      = {Cell $\&$ bioscience},
      volume       = {13},
      number       = {1},
      issn         = {2045-3701},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-01744},
      pages        = {155},
      year         = {2023},
      abstract     = {Pain in early life may impact on development and risk of
                      chronic pain. We developed an optogenetic Cre/loxP mouse
                      model of 'early-life-pain' (ELP) using mice with transgenic
                      expression of channelrhodopsin-2 (ChR2) under control of the
                      Advillin (Avil) promoter, which drives expression of
                      transgenes predominantly in isolectin B4 positive
                      non-peptidergic nociceptors in postnatal mice. Avil-ChR2
                      (Cre +) and ChR2-flfl control mice were exposed to blue
                      light in a chamber once daily from P1-P5 together with their
                      Cre-negative mother.ELP caused cortical hyperexcitability at
                      P8-9 as assessed via multi-electrode array recordings that
                      coincided with reduced expression of synaptic genes (RNAseq)
                      including Grin2b, neurexins, piccolo and voltage gated
                      calcium and sodium channels. Young adult (8-16 wks)
                      Avil-ChR2 mice presented with nociceptive hypersensitivity
                      upon heat or mechanical stimulation, which did not resolve
                      up until one year of age. The persistent hypersensitivy to
                      nociceptive stimuli was reflected by increased calcium
                      fluxes in primary sensory neurons of aged mice (1 year) upon
                      capsaicin stimulation. Avil-ChR2 mice behaved like controls
                      in maze tests of anxiety, social interaction, and spatial
                      memory but IntelliCage behavioral studies revealed
                      repetitive nosepokes and corner visits and compulsive
                      lickings. Compulsiveness at the behavioral level was
                      associated with a reduction of sphingomyelin species in
                      brain and plasma lipidomic studies. Behavioral studies were
                      done with female mice.The results suggest that ELP may
                      predispose to chronic 'pain' and compulsive psychopathology
                      in part mediated by alterations of sphingolipid metabolism,
                      which have been previously described in the context of
                      addiction and psychiatric diseases.},
      keywords     = {Calcium (Other) / Compulsive behavior (Other) / Cortical
                      excitability (Other) / IntelliCage (Other) / Multichannel
                      electrode arrays (Other) / Nociception (Other) / Optogenetic
                      (Other) / Repetitiveness (Other)},
      cin          = {FM01},
      ddc          = {050},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37635256},
      doi          = {10.1186/s13578-023-01106-3},
      url          = {https://inrepo02.dkfz.de/record/282360},
}