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. 2016 Feb 3;7:10604. doi: 10.1038/ncomms10604

Figure 5. Membrane permeable mGluR5 antagonist reduces pain and Fos.

Figure 5

(a) LY393053 (1–1,000 nmol) weakly attenuates glutamate-induced pain behaviours in SNI rats (at the 10 nmol dose only, P=0.0362), but not sham rats (vehicle, veh). N=6 rats per group. (b) Fenobam (1–100 nmol) dose-dependently attenuates glutamate-induced pain behaviours in both sham and SNI rats (ANOVA *P<0.05, **P<0.01, ***P<0.001). N=6 rats per group. (c) Fenobam (100 nmol) or fenobam+CPCCOEt (100 nmol) reduce glutamate-induced pain behaviours significantly more than LY393053 (100 nmol) in SNI rats. (ANOVA ***P<0.001 with respect to LY393053). Conversely, drug effects are equivalent in sham rats. N=6 rats/group. Fenobam/LY393053 (100 nmol) data repeated from a and b. (d) Paw withdrawal thresholds (PWTs) of SNI rats are increased by fenobam, but not LY393053 (each 100 nmol), (ANOVA 30-min P<0.001; 60-min P=0.0156) ***P<0.001 versus vehicle, P<0.05, †††P<0.001 with respect to LY393053 (legend as in e) N=8 rats per group. (e) Neither fenobam nor LY393053 affect PWTs of sham rats. N=8 rats per group (f) SNI, but not naive, rats show conditioned place preference (CPP) to fenobam (200 nmol), (ANOVA CPP index=62.51%, P=0.0099; **P<0.01), but not LY393053 (1 μmol). Consequently, fenobam exhibits significantly greater CPP than LY393053 (††P<0.01 fenobam versus LY393053). N=8 rats/group. (g) Representative glutamate-induced Fos in ipsilateral SCDH (outlined with dashed lines) of sham and SNI animals after spinal pretreatment with fenobam or LY393053. Scale bar, 100 μm. (h) Glutamate-induced Fos in ipsilateral SCDH of SNI rats is reduced by fenobam (ANOVA P=0.0024 versus glutamate), but not LY593053 (**P<0.01 with respect to vehicle). Consequently, fenobam-treated rats exhibited significantly lower Fos than LY393053-treated rats (ANOVA P=0.0258 versus LY393053, P<0.05 with respect the LY393053). Fos expression was unaffected by either fenobam or LY393053 in sham rats. Six to 12 sections were averaged per animal, with N=6 animals/group. (i) Representative glutamate-induced Jun in ipsilateral-SCDH (outlined with dashed lines) of sham and SNI animals following pretreatment with fenobam or LY393053 (100 nmol each). Scale bar, 100 μm. (j) Jun is reduced by either fenobam or LY393053 in both sham and SNI rats (ANOVA sham P=0.0074; SNI P=0.0060) or LY393053 (sham P=0.0154; SNI P<0.0001). (*P<0.05; ***P<0.001). Six to 12 sections were averaged for each animal, with N=6 animals per group. All values in figure are expressed as mean±s.e.m.