Islet amyloid polypeptide and calcitonin gene-related peptide expression are upregulated in lumbar dorsal root ganglia after unilateral adjuvant-induced inflammation in the rat paw

Abstract

After unilateral adjuvant-induced inflammation, expression of neuropeptides believed to be involved in the inflammatory response, e.g. substance P and calcitonin gene-related peptide (CGRP), is upregulated in innervating sensory neurons. Islet amyloid polypeptide (IAPP) is structurally related to CGRP and constitutively expressed in sensory CGRP-containing neurons; the role of IAPP in sensory neurons is unknown. To examine whether IAPP could play a role in inflammation, IAPP expression in L 5 dorsal root ganglion (DRG) and its distribution in the dorsal horn were investigated after unilateral adjuvant-induced inflammation in the rat paw and compared with CGRP, using in situ hybridization and immunocytochemistry. At 12 h and day 3, but not day 21, the percentage of nerve cell profiles expressing IAPP and CGRP mRNA was greater in the ipsilateral L 5 DRG; these changes paralleled the occurrence of edema around the tarsotibial joint and a slight limp. IAPP expression in individual nerve cell profiles was higher in the ipsilateral L 5 DRG at 12 h, but not at days 3 and 21; the corresponding CGRP mRNA level was higher at days 3 and 21. At day 3, the higher expression of IAPP and CGRP on the ipsilateral side was accompanied by increased numbers of immunoreactive DRG neurons and fibers in the spinal cord dorsal horn. Largely, expression of IAPP and CGRP seems to be co-ordinately regulated by localized inflammation, although the rapid, but transient, upregulation in DRG neurons of IAPP mRNA expression and the slower, but sustained, upregulation of CGRP mRNA expression may indicate dissociated regulation of the peptides. Thus, IAPP could play a role in the initial phase of localized inflammation.