Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb;155(2):377-387.
doi: 10.1016/j.pain.2013.10.026. Epub 2013 Nov 8.

Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain

Kun-Long Hung  1 , Su-Jane Wang, Ying-Chou Wang, Tsuey-Ru Chiang, Chia-Chuan Wang
Affiliations

Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain

Kun-Long Hung et al. Pain. 2014 Feb.

Abstract

Although nerve injury-induced long-term postsynaptic changes have been investigated, less is known regarding the molecular mechanisms within presynaptic axonal terminals. We investigated the molecular changes in presynaptic nerve terminals underlying chronic pain-induced plastic changes in the medial prefrontal cortex (mPFC). After neuropathic pain was induced by spared nerve injury (SNI) in rats, we assessed the release of the excitatory neurotransmitter glutamate by using in vitro synaptosomal preparations from the mPFC. We also measured the levels of synaptic proteins and protein kinases in synaptosomes using Western blotting. The results showed that unilateral long-term SNI augmented depolarization-evoked glutamate release from synaptosomes of the bilateral mPFC. This result was confirmed by a rapid destaining rate of FM1-43 dye in SNI-operated rats. Unilateral long-term nerve injury also significantly increased synaptic proteins (including synaptophysin, synaptotagmin, synaptobrevin, syntaxin, and 25-kDa synaptosome-associated protein) in synaptosomal fractions from the bilateral mPFC, and ultrastructure images demonstrated increased synaptic vesicular profiles in synaptosomes from SNI animals. Chronic pain upregulated the phosphorylation of endogenous protein kinases, including extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Ca(2+)/calmodulin-dependent kinase II (CaMKII), and synapsin I, the primary presynaptic target of ERK1/2 and CaMKII. Both presynaptic proteins and protein kinases were upregulated after SNI in a time-dependent manner. These results indicate that the long-term neuropathic pain-induced enhancement of glutamate release in the mPFC is linked to increased synaptic vesicle proteins and the activation of the ERK1/2- and CaMKII-synapsin signaling cascade in presynaptic axonal terminals.

Keywords: Glutamate; Medial prefrontal cortex; Neuropathic pain; Protein kinase; Synaptic proteins; Synaptosome.

PubMed Disclaimer

References

    1. Antonova I, Arancio O, Trillat AC, Wang HG, Zablow L, Udo H, Kandel ER, Hawkins RD. Rapid increase in clusters of presynaptic proteins at onset of long-lasting potentiation. Science 2001;294:1547-1550.
    1. Apkarian AV, Sosa Y, Krauss BR, Thomas PS, Fredrickson BE, Levy RE, Harden RN, Chialvo DR. Chronic pain patients are impaired on an emotional decision-making task. PAIN® 2004;108:129-136.
    1. Betz WJ, Mao F, Bewick GS. Activity-dependent fluorescent staining and destaining of living vertebrate motor nerve terminals. J Neurosci 1992;12:363-375.
    1. Boyken J, Gronborg M, Riedel D, Urlaub H, Jahn R, Chua JJ. Molecular profiling of synaptic vesicle docking sites reveals novel proteins but few differences between glutamatergic and GABAergic synapses. Neuron 2013;78:285-297.
    1. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-254.

Publication types

LinkOut - more resources