Calcitonin gene-related peptide gene expression in collagen-induced arthritis is differentially regulated in primary afferents and motoneurons: influence of glucocorticoids
| Autor: | G. Ekström, Horacio Romeo, C. Post, D. Nohr, Fred Nyberg, Eberhard Weihe, S. Persson, Martin K.-H. Schäfer |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Administration Topical Calcitonin Gene-Related Peptide Anti-Inflammatory Agents Neuropeptide Arthritis In situ hybridization Calcitonin gene-related peptide Internal medicine Gene expression medicine Image Processing Computer-Assisted Animals Neurons Afferent RNA Messenger Calcitonin receptor Budesonide Glucocorticoids In Situ Hybridization Motor Neurons Neurogenic inflammation Chemistry General Neuroscience medicine.disease Arthritis Experimental Immunohistochemistry Rats Endocrinology Gene Expression Regulation Spinal Cord Calcitonin Female Collagen |
| Zdroj: | Neuroscience. 93(2) |
| ISSN: | 0306-4522 |
| Popis: | Calcitonin gene-related peptide is involved in peripheral and spinal mechanisms of inflammatory pain. In this paper, we used collagen II-induced arthritis in the rat as a model to investigate the influence of chronic arthritic pain on calcitonin gene-related peptide gene expression in sensory and motor pathways. Additionally, we examined the effect of the glucocorticoid drug budesonide on arthritis-induced changes of calcitonin gene-related peptide expression and constitutive calcitonin gene-related peptide expression. Thirteen days after the immunization with native rat collagen type II rats developed a progressive and chronic polyarthritis which was scored with respect to the degree of swelling and/or redness of the paw and ankle joints. Budesonide significantly attenuated the extent of arthritis. Changes in calcitonin gene-related peptide expression were evaluated by semiquantitative in situ hybridization and immunocytochemistry on day 21 post-immunization. In sensory neurons of dorsal root ganglia of arthritic rats, a significant increase in calcitonin gene-related peptide messenger RNA and protein levels was seen. These increases were completely blocked by budesonide. Also in dorsal root ganglia of non-arthritic rats, budesonide had an effect, with reduced calcitonin gene-related peptide messenger RNA levels below constitutive concentrations. Image analysis of calcitonin gene-related peptide immunoreactivity revealed that changes in calcitonin gene-related peptide expression were due to alterations in calcitonin gene-related peptide expression levels rather than to de novo synthesis or changes in the numbers of calcitonin gene-related peptide expressing neurons. In spinal motoneurons of arthritic rats, marked decreases in calcitonin gene-related peptide messenger RNA and protein levels were measured. These reductions were attenuated by budesonide. The changes in calcitonin gene-related peptide expression in motoneurons correlated with the severity of arthritis in the ipsilateral hind paw. Budesonide had no effects on calcitonin gene-related peptide messenger RNA levels in motoneurons of non-arthritic rats. The opposite regulation of calcitonin gene-related peptide gene expression in primary sensory and spinal somatomotor pathways in collagen-induced arthritis suggests that calcitonin gene-related peptide plays a specific role in both chronic inflammatory pain and arthritis-induced motor dysfunction. The sensitivity of constitutive and inflammation-induced sensory calcitonin gene-related peptide expression to budesonide treatment may indicate that the beneficial effects of steroid treatment in inflammation is partly mediated by down-regulation of calcitonin gene-related peptide in sensory neurons involved in neurogenic inflammation. |
| Databáze: | OpenAIRE |
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