STREPTOZOTOCIN-INDUCED DIABETES IS ASSOCIATED WITH ALTERED EXPRESSIONOF PEPTIDE-ENCODING MESSENGER-RNAS IN RAT SENSORY NEURONS

Major complications arising from diabetes mellitus include neuropathic pain and altered peripheral inflammatory responses. Somatostatin (SOM ), calcitonin gene-related peptide (CGRP), and substance P (SP) are ne uropeptides that modulate pain responses transmitted by primary sensor y afferents, the cell bodies of which are located in the dorsal root g anglion (DRG). Thus, the goal of the present study was to determine wh ether the diabetic condition is associated with altered neuropeptide g ene expression in lumbar DRG of the rat. We employed an established an imal model in which streptozotocin (STZ, 55 mg/kg) is administered to 6-week-old rats. The hallmark symptoms of hyperglycemia (blood glucose > 400 mg/dl), polydipsia, polyuria, and severe weight loss were maxim al at 6 weeks postadministration, at which time animals were sacrifice d. For determination of peptide-encoding mRNAs distributed in DRG neur ons, in situ hybridization histochemistry utilizing S-35-end-labeled o ligonucleotides complimentary to sequences of preprosomatostatin (PPSO M), preprocalcitonin gene related peptide (PPCGRP), preprotachykinin ( PPT), or preproneuropeptide Y (PPNPY) mRNA was performed. Silver grain s were detected overlying DRG cells by autoradiography on sections of tissue counterstained with thionin. Semiquantitative analysis of diffe rences in silver grain signal were made using an image analysis system , which expressed signals as fCi/mu m(2). In diabetic rats there was a significant decrease in DRG PPSOM (54%, p < 0.01), and PPCGRP (33%, p < 0.05) mRNA hybridization from the normal values. PPT mRNA hybridiza tion signal and SP-like immunoreactivity were not significantly change d in diabetic rat DRGs compared to control. In contrast, there was an increase in the number of cells labeled with PPNPY hybridization in DR G from diabetic rats. These data suggest that CGRP and SOM synthesis i n primary sensory neurons is reduced in STZ-induced diabetic rats. The se changes could contribute to the painful neuropathies and altered in flammatory responses seen in diabetes mellitus.