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. 2014 Oct 29;34(44):14739–14751. doi: 10.1523/JNEUROSCI.0860-14.2014

Figure 6.

Figure 6.

Blockade of BDNF/TrkB signaling by intra-ACC injection of TrkB antagonist prevented the cold hypersensitivity and cortical hyperexcitability induced by peripheral inflammation. A–D, Blockade of the BDNF/TrkB signaling pathway by the antagonist CTX-B prevented the occurrence of cold allodynia in CFA-injected rats (A). It also temporarily prevented the development of cold hyperalgesia for 2 d (B), but had no effect on the mechanical allodynia observed in the hindpaw ipsilateral to CFA injection (C). Neither intraplantar injection of CFA into the right paw nor intra-ACC injection of CTX-B modified the withdrawal threshold for the contralateral hindpaw (D, left). E–F, Representative examples of pERK staining in the cingulate cortex in a control (E) and a CFA-treated (F) rat. Arrows indicate pERK positive neurons. Scale bar, 90 μm. G, Quantification of pERK-positive neurons, showing that the antagonistic effect of CTX-B on BDNF-TrkB signaling prevented a peripheral inflammation-evoked increase in the number of pERK neurons in the ACC. H, Representative photomicrographs of pERK and BDNF immunostainings and colocalisation (arrows) in neurons of the cingulate cortex. Scale bar, 40 μm. All data are expressed as mean ± SEM; N = 6 animals per group, three-way ANOVA, followed by a Student-Newman–Keuls post hoc test. A, Inflammation treatment parameter: F(1,116) = 9.334, p = 0.003; CTX-B treatment parameter: F(1,116) = 4.213, p = 0.043; B, Inflammation treatment parameter: F(1,116) = 106.608, p < 0.001; CTX-B treatment parameter: F(1,116) = 7.245, p = 0.008; C, Inflammation treatment parameter: F(1,116) = 236.029, p < 0.001; CTX-B treatment parameter: F(1,116) = 1.104, p = 0.296; **p < 0.01 CFA-saline versus saline-saline rats; §p < 0.05 CFA-saline versus CFA-CTX-B rats. D, *p < 0.05, **p < 0.01, ***p < 0.001 CFA-saline versus saline-saline rats; ††p < 0.01, †††p < 0.001 CFA-CTX-B versus saline-CTX-B rats; §p < 0.05, §§§p < 0.001 CFA-saline versus CFA-CTX-B rats. G, F(3,20) = 5.875, p = 0.006.