Expression and functional characterization of transient receptor potential vanilloid 4 in the dorsal root ganglion and spinal cord of diabetic rats with mechanical allodynia

摘要

Diabetic mechanical allodynia (DMA) is a common manifestation in patients with diabetes mellitus, and currently, no effective treatment is available. Transient receptor potential vanilloid 4 (TRPV4) is involved in mechanical hypersensitivity resulting from varying aetiologies in animal, but its expression pattern during DMA and whether it contributes to this condition are still unclear. We investigated the spatial and temporal expression patterns of TRPV4 in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) by qRT-PCR, Western blotting and immunofluorescence assays. The pathophysiological role of TRPV4 in DMA was also investigated by intrathecal application of the TRPV4 selective antagonist HC-067047 or the agonist GSK1016790A. The results showed that both the mRNA and protein levels of TRPV4 were strikingly upregulated on day 14 in the rats with DMA. The increase in TRPV4 was mainly observed in the soma and central processes of calcitonin gene-related peptide (CGRP)- or neurofilament 200 kDa (NF200)-containing DRG neurons. Both single and repetitive intrathecal applications of HC-067047 (400 ng/kg) significantly alleviated mechanical allodynia in the rats with DMA, whereas a single application of GSK1016790A (200 ng/kg) aggravated mechanical allodynia. The present data suggest that TRPV4 undergoes expression changes that are associated with mechanical hypersensitivity in diabetic rats. TRPV4 may be a new molecular target for developing a clinical strategy to treat this intractable neuropathic pain.