Phenotypic Inflammation Switch in Rats Shown by Calcitonin Gene-Related Peptide Immunoreactive Dorsal Root Ganglion Neurons Innervating the Lumbar Facet Joints


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Abstract

Study Design. The changes in dorsal root ganglion neurons innervating the L5–L6 facet joint were studied using the retrograde neurotransport method and the immunohistochemistry of calcitonin gene-related peptide in an inflammatory model of rats.Objectives.To determine by inflammatory stimulation the changes in calcitonin gene-related peptide–immunoreactive dorsal root ganglion neurons innervating the L5–L6 facet.Summary of Background Data. The rat L5–L6 facet joint is innervated from L1–L5 dorsal root ganglia. The presence of calcitonin gene-related peptide–immunoreactive dorsal root ganglion neurons innervating the L5–L6 facet joint has been confirmed, but the changes in the number and distribution of these neurons caused by inflammation have not been studied.Methods.Retrograde transport of fluorogold was used in 20 rats: 10 in the control group and 10 in the inflammatory group. Using the dorsal approach, fluorogold crystals were injected into the left L5–L6 facet joint. Then 5 days after application, complete Freund’s adjuvant (50 μg Mycobacterium butyricum in oil saline emulsion) was injected into the same L5–L6 facet joint (inflammatory group). Of the total fluorogold-labeled dorsal root ganglion neurons from T13–L6, the number and cross-sectional area of the cell profiles of fluorogold-labeled, calcitonin gene-related peptide–immunoreactive neurons in the bilateral dorsal root ganglia of both groups were evaluated.Results.Fluorogold-labeled neurons were distributed throughout the ipsilateral dorsal root ganglia from L1–L5 in both groups. Of the fluorogold-labeled neurons, the ratios of the calcitonin gene-related peptide–immunoreactive L1, L2, L3, L4, and L5 dorsal root ganglion neurons, respectively, were 17%, 24%, 44%, 56%, and 50% in the control group and 50%, 39%, 51%, 61%, and 56% in the inflammatory group. The ratios of the calcitonin gene-related peptide–immunoreactive L1 and L2 dorsal root ganglion neurons labeled by fluorogold were significantly higher in the inflammatory group than in the control group (P < 0.05). The mean cross-sectional area of fluorogold-labeled, calcitonin gene-related peptide–immunoreactive cells from L1–L5 dorsal root ganglia increased from 621 ± 64 μm2 to 893 ± 63 μm2 in the inflammatory group (P < 0.01).Conclusions.The ratio of fluorogold-labeled, calcitonin gene-related peptide–immunoreactive neurons was significantly higher in the L1 and L2 dorsal root ganglia of the inflammatory group than in those of the control group, and the average cross-sectional area of the cells from L1–L5 dorsal root ganglion increased. Associated with the inflammation in the facet joints, the change in calcitonin gene-related peptide–immunoreactive neuron distribution and the phenotypic switch to large neurons may complicate the mechanism of facet joint inflammatory pain.

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