Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice

Abstract

Background: (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. It has been reported that may be a natural agent for reducing thermal and mechanical pain after nervous system injuries. However, the molecular pathways implicated in these beneficial effects have not been completely elucidated. This study aimed to assess the EGCG treatment effects on thermal hyperalgesia, spinal cord gliosis and modulation of Ras homologue gene family member A (RhoA), fatty acid synthase (FASN) and tumour necrosis factor alpha (TNF-α) expression after spinal cord contusion in mice.

Methods: Animals were subjected to a spinal cord contusion. Thirty minutes after contusion and daily during the first week post-surgery, animals were treated with EGCG or dimethyl sulfoxide-saline (DMSO-saline). At 7 and 14 days post-operation, motor recovery was evaluated using the Basso Mouse Scale, and nociceptive response was evaluated using the Hargreaves test. Furthermore, at 14 days, the expression of RhoA, FASN and TNF-α proteins was quantified in the lesion site of spinal cord by Western blot technique. Finally, spinal cord samples were processed by immunohistochemical techniques for observing astrocytes, microglia and afferent nerve fibres.

Results: At short time, EGCG treatment reduced significantly thermal hyperalgesia but had no effect on locomotor recovery in spinal cord injured mice. Furthermore, EGCG treatment down-regulated the RhoA, FASN and TNF-α proteins expression, and decreased astro- and microglia reactivity in spinal cord.

Conclusion: These findings suggest that at short time EGCG treatment reduces thermal hyperalgesia and gliosis via FASN and RhoA pathway, causing a decrease in cytokines in spinal cord.