In the absence of HINT1 proteins, CCI promotes the destruction of α2δ1-2 proteins when associated to NMDARs. (A) 129 WT sham-operated (n = 7), 129 WT CCI (n = 7), 129 HINT1−/− sham (n = 7), and 129 HINT1−/− CCI mice (n = 7) were sacrificed 7 days after surgery to obtain PAG synaptosomal fractions. NR1 subunits were immunoprecipitated (IP) from the solubilized membrane preparations and the presence of co-precipitated (A) NR1 subunits carrying cytosolic C1 segment, (B) NR2B subunits, (C) α2(δ1) proteins of 150 kDa, (D) (α2)δ1 peptides, (E) α2(δ1) proteins of 75 kDa, and (F) σ1Rs were assessed in Western blot (WB). The bars represent the mean ± SD of three measurements and the data are shown relative to the 129 WT sham mice (assigned the arbitrary value of 1). Determination of σ1R: due to the weak signal observed in 129 WT sham mice, the data were assessed relative to the 129 HINT1−/− sham mice (arbitrary value of 1). The arrows refer to the comparison and * indicates significant difference of the CCI group relative to the 129 WT or 129 HINT1−/− control group: p < 0.05.