engleski

Depression of Ca2+/Calmodulin-Dependent Protein Kinase II in Dorsal Root Ganglion Neurons after Spinal Nerve Ligation

The enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) is associated with memory and its isoform is critical for development of activity-induced synaptic changes. Therefore, we hypothesized that CaMKII is involved in altered function of dorsal root ganglion (DRG) neurons after neuronal injury. To test this hypothesis, Sprague-Dawley rats were made hyperalgesic by L5 and L6 spinal nerve ligation (SNL), and changes in total phosphorylated and unphosphorylated CaMKII (tCaMKII) and phosphorylated form of its isoform (pCaMKII) were analyzed using immunochemistry in different subpopulations of DRG. SNL did not induce any changes in tCaMKII between experimental groups, while the overall percentage of pCaMKII-positive neurons in injured L5 DRG SNL (24.8%) decreased significantly when compared to control (41.7%). SNL did not change the percentage of pCaMKII/N52 colabeled neurons but decreased the percentage of N52-negative nonmyelinated neurons that expressed pCaMKII from 27% in control animals to 11% after axotomy. We also observed a significant decrease in the percentage of small nonpeptidergic neurons labeled with IB4 (37.6% in control vs. 4.0% in L5 SNL DRG), as well as a decrease in the percentage of pCaMKII/IB4 colabeled neurons in injured L5 DRGs (27% in control vs. 1% in L5 DRG of SNL group). Our results show that reduction in pCaMKII levels following peripheral injury is due to the loss of IB4-positive neurons. These results indicate that diminished afferent activity after axotomy may lead to decreased phosphorylation of CaMKII.

neuropathic pain; spinal nerve ligation; primary sensory neurons; calcium/calmodulin-dependent protein kinase II

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