The effect of streptozotocin-induced diabetes mellitus on substance P and calcitonin gene-related peptide expression in the rat trigeminal ganglion

Substance P (SP) and calcitonin gene-related peptide (CGRP) constitute the main sensory peptides in the trigeminal ganglion (TG). The objective of thi s study was to characterize peptidergic changes in the streptozotocin-induc ed diabetes mellitus rat model both quantitatively and qualitatively. Diabe tes mellitus was induced by a single intraperitoneal injection of streptozo tocin (65 mg/kg) and the levels of SP and CGRP were measured by means of ra dioimmunoassay (RIA) in a time-dependent manner. Peptide immunoreactivities were characterized by high pressure liquid chromatography (HPLC). The expr ession of both neuropeptides was examined 5 weeks after streptozotocin inje ction using in situ hybridization with S-35-labelled oligonucleotides. Sali ne-injected rats served as controls. SP was significantly decreased in the diabetic rat TG, i.e., a 44.6% (+/- 10.9) decrease after 1 week, 40.2% (+/- 11.8) after 3 weeks and 72.3% (+/- 14.6) after 5 weeks. CGRP was decreased only after 5 weeks (19.6% decrease +/- 3.9), whereas at later stages, both peptide levels returned to normal values. HPLC revealed one major peak coe luting with the synthetic peptides. By using in situ hybridization, a signi ficantly increased signal of both peptide-encoding mRNAs was found (43.8%), which seems to act to restore a diabetes-associated depletion of neuropept ides in the diabetic rat TG. The decreased SP- and CGRP levels in the diabe tic rat TG reflect a diabetes-associated deficit which may be clinically re levant. Diabetes mellitus is associated with a variety of ocular complicati ons, even corneal complications, including decreased corneal sensitivity, w hich in many ways resemble those after interruption of the normal trophic i nnervation of the eve. Our results point to reduced availability of neurope ptides for corneal innervation and may thus support the idea of a partial l oss of trophic influences from the bigeminal nerve in diabetics. (C) 1999 E lsevier Science B.V. All rights reserved.