title: Nociceptive stimulation induces expression of Arc/Arg3.1 in the spinal cord with a preference for neurons containing enkephalin.
abstract: BACKGROUND
  In pain processing, long term synaptic changes play an important role, especially during chronic pain. The immediate early gene Arc/Arg3.1 has been widely implicated in mediating long-term plasticity in telencephalic regions, such as the hippocampus and cortex. Accordingly, Arc/Arg3.1 knockout (KO) mice show a deficit in long-term memory consolidation. Here, we identify expression of Arc/Arg3.1 in the rat spinal cord using immunohistochemistry and in situ hybridization following pain stimuli.
  
  
  RESULTS
  We found that Arc/Arg3.1 is not present in naïve or vehicle treated animals, and is de novo expressed in dorsal horn neurons after nociceptive stimulation. Expression of Arc/Arg3.1 was induced in an intensity dependent manner in neurons that were located in laminae I (14%) and II (85%) of the spinal dorsal horn. Intrathecal injection of brain derived neurotrophic factor (BDNF) also induced expression of Arc/Arg3.1. Furthermore, 90% of Arc/Arg3.1 expressing neurons also contained the activity marker c-Fos, which was expressed more abundantly. Preproenkephalin mRNA was found in the majority (68%) of the Arc/Arg3.1 expressing neurons, while NK-1 was found in only 19% and GAD67 mRNA in 3.6%. Finally, pain behavior in Arc/Arg3.1 KO mice was not significantly different from their wild type littermates after application of formalin or after induction of chronic inflammatory pain.
  
  
  CONCLUSIONS
  We conclude that Arc/Arg3.1 is preferentially expressed in spinal enkephalinergic neurons after nociceptive stimulation. Therefore, our data suggest that Arc/Arg3.1 dependent long term synaptic changes in spinal pain transmission are a feature of anti-nociceptive, i.e. enkephalinergic, rather than pro-nociceptive neurons.
authors.affiliation: Dept, of Neuroscience, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hossaini
authors.forename: Joost L M
authors.initials: JL
authors.lastname: Jongen
authors.forename: Karla
authors.initials: K
authors.lastname: Biesheuvel
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Jan C
authors.initials: JC
authors.lastname: Holstege
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D004558:Electric Stimulation; D004745:Enkephalins / Q000378:metabolism*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D004745:Enkephalins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein