Calcitonin gene-related peptide gene expression in collagen-induced arthritis is differentially regulated in primary afferents and motoneurons: Influence of glucocorticoids

Calcitonin gene-related peptide is involved in peripheral and spinal mechan isms of inflammatory pain. In this paper, we used collagen II-induced arthr itis in the rat as a model to investigate the influence of chronic arthriti c pain on calcitonin gene-related peptide gene expression in sensory and mo tor pathways. Additionally, we examined the effect of the glucocorticoid dr ug budesonide on arthritis-induced changes of calcitonin gene-related pepti de 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 res pect to the degree of swelling and/or redness of the paw and ankle joints. Budesonide significantly attenuated the extent of arthritis. Changes in cal citonin 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 level s was seen. These increases were completely blocked by budesonide. Also in dorsal root ganglia of non-arthritic rats, budesonide had an effect, with r educed calcitonin gene-related peptide messenger RNA levels below constitut ive concentrations. Image analysis of calcitonin gene-related peptide immun oreactivity revealed that changes in calcitonin gene-related peptide expres sion were due to alterations in calcitonin gene-related peptide expression levels rather than to de novo synthesis or changes in the numbers of calcit onin gene-related peptide expressing neurons. In spinal motoneurons of arth ritic rats, marked decreases in calcitonin gene-related peptide messenger R NA and protein levels were measured. These reductions were attenuated by bu desonide. The changes in calcitonin gene-related peptide expression in moto neurons correlated with the severity of arthritis in the ipsilateral hind p aw. 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 arth ritis suggests that calcitonin gene-related peptide plays a specific role i n both chronic inflammatory pain and arthritis-induced motor dysfunction. T he sensitivity of constitutive and inflammation-induced sensory calcitonin gene-related peptide expression to budesonide treatment may indicate that t he beneficial effects of steroid treatment in inflammation is partly mediat ed by down-regulation of calcitonin gene-related peptide in sensory neurons involved in neurogenic inflammation. (C) 1999 IBRO. Published by Elsevier Science Ltd.