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.

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Keywords Wistar rat, activity regulated cytoskeletal-associated protein, activity regulated cytoskeleton associated protein, animal, animal experiment, animal model, animal tissue, article, biosynthesis, brain derived neurotrophic factor, cellular distribution, chronic pain, controlled study, cytoskeleton protein, drug effect, electrostimulation, enkephalin, gene expression, genetics, glutamate decarboxylase 67, heat, immunohistochemistry, in situ hybridization, male, messenger RNA, metabolism, mouse, mouse mutant, nerve protein, neuropathic pain, nociceptive receptor, nociceptive stimulation, nonhuman, pain, pain threshold, pathophysiology, physiology, posterior horn cell, priority journal, protein c fos, protein expression, protein localization, quantitative analysis, rat, spinal cord, spinal cord dorsal horn, spinal cord nerve cell, synaptic transmission, wild type
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Journal Molecular Pain
Hossaini, S.M, Jongen, J.L.M, Biesheuvel, K, Kuhl, D, & Holstege, J. (2010). Nociceptive stimulation induces expression of Arc/Arg3.1 in the spinal cord with a preference for neurons containing enkephalin. Molecular Pain, 6(23), 1–13. doi:10.1186/1744-8069-6-43