Neuroplastic changes within the spinal cord have been associated with the development of OIH and opioid tolerance, and many genes undergo changes in spinal cord gene expression after chronic morphine exposure [31]. Furthermore, DCC protein levels in the CNS were observed to be altered after repeated exposure to amphetamines [32]. Therefore, we hypothesized that morphine alters Dcc expression in mouse spinal cord tissue after repeated exposure. However, the levels of Dcc expression in the spinal cord of C57BL/6 J mice (a morphine adaptive strain) and in a very adaptation-resistant strain (129S1) were unchanged after morphine treatment measured at both the mRNA and protein levels (Figure 6). In addition, the DCC protein levels in spinal cord tissue in these two strains were indistinguishable under control conditions.
