Molecular and immunohistochemical studies in expression of voltage-dependent Ca2+ channels in dorsal root ganglia from streptozotocin-induced diabetic mice

摘要

We have recently demonstrated that intrathecal injection of a selective P/Q-type blocker of the voltage-dependent Ca2+ channels (VDCCs) significantly inhibited the mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic mice, its antinociceptive effect being greater than in controls. In this study, to further clarify the underlying mechanism of the STZ-induced byperalgesia, we investigated the expression level of the VDCC alpha 1A and alpha 1B subunits in the dorsal root ganglia (DRGs) and the dorsal spinal cord under this hyperalgesia, Real-time PCR analysis showed mRNA expression of alpha 1A (P/Q-type), but not alpha 1B (N-type), was significantly increased in the DRGs from the STZ-induced diabetic mice. On the other hand, gene expression of both alpha 1 subunits was not changed in the dorsal part of the spinal cord. In diabetic DRG neurons, the number of large nerve cells was significantly reduced, whereas small neurons were significantly increased. Immunohistochemical study demonstrated the alpha 1A-positive neurons, but not alpha 1B-positive neurons, increased significantly greater in diabetic DRGs than in control in all cell size. These results indicate that an alteration in expression of P/Q-type VDCCs, especially in the small and medium-diameter primary afferent fibers, in pain pathways ascending input to the spinal cord may be involved in hypersensitivity in STZ-induced diabetes. (c) 2006 Elsevier Inc. All rights reserved.