http://dx.doi.org/10.1186/1744-8069-6-43
scopus: cited 2 times
web of science: cited 2 times
Nociceptive stimulation induces expression of Arc/Arg3.1 in the spinal cord with a preference for neurons containing enkephalin
July 2010
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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.
- article
- male
- metabolism
- priority journal
- controlled study
- genetics
- animal experiment
- animal model
- animal tissue
- drug effect
- mouse
- nonhuman
- animal
- quantitative analysis
- gene expression
- rat
- physiology
- protein expression
- pathophysiology
- wild type
- messenger RNA
- protein localization
- immunohistochemistry
- pain
- chronic pain
- neuropathic pain
- Wistar rat
- activity regulated cytoskeletal-associated protein
- activity regulated cytoskeleton associated protein
- biosynthesis
- brain derived neurotrophic factor
- cellular distribution
- cytoskeleton protein
- electrostimulation
- enkephalin
- glutamate decarboxylase 67
- heat
- in situ hybridization
- mouse mutant
- nerve protein
- nociceptive receptor
- pain threshold
- nociceptive stimulation
- posterior horn cell
- protein c fos
- spinal cord dorsal horn
- spinal cord nerve cell
- synaptic transmission
- spinal cord
- neuron
- arc /arg mrna
- arc /arg
- dorsal horn
- expression
- dorsal
- protein
- number
- injection
- survival
- enkephalinergic neurons
- dorsal horn neurons
- stimulation
- receptor
- experiment
- hossaini
- section
- 3.1
- mustard
- ± sem