Contribution of BDNF/TrkB pathway to development of neuropathic pain by activation of astrocytes in rats
Objective: To investigate the effects of exogenous brain-derived neurotrophic factor(BDNF) on mechanical pain threshold and astrocytes, and explore the potential mechanism of BDNF-induced pain. Methods: Thirty rats with successful intrathecal catheterization were randomly divided into blank control group, placebo group, BDNF group, BDNF+ astrocyte inhibitor group(BDNF+fluorocitrate group) and BDNF+tyrosine kinase receptor B(TrkB) inhibitor group(BDNF +K252a group), with 6 rats in each group. Intrathecal administration was performed once daily for 7 d. Fifty percent paw withdrawal threshold(50%PWT) was measured 1 h before each injection. Spinal enlargement parts were obtained 1 h after the last administration, and the expression of glial fibrillary acidic protein(GFAP) and phosphorylated TrkB protein was detected by Western blotting. Results: Compared with blank control group, 50%PWT of hind limbs in BDNF group was significantly lower(P < 0.05). Seven days after administration, the expression of GFAP and phosphorylated TrkB protein in spinal enlargement parts in BDNF group was significantly higher than that in blank control group(P < 0.01). The expression of GFAP protein and 50%PWT in BDNF+fluorocitrate group and BDNF+K252a group were not significantly different from those in blank control group(P > 0.05). There was no significant difference in the expression of phosphorylated TrkB protein between BDNF+K252a group and blank control group(P > 0.05). Conclusion: BDNF may activate astrocytes via phosphorylated TrkB receptor, which in turn produce neuropathic pain.