Despite the difference in DCC protein expression in the spinal cord, Dcc heterozygous and wild type mice did not differ in their basal (prior to morphine treatment) nociceptive responses to thermal and mechanical stimuli, nor in the extent of opioid analgesia observed after acute administration of morphine to drug naïve mice (Figure 4). In contrast, wild-type mice displayed markedly reduced threshold levels of mechanical hypersensitivity after chronic opioid treatment (i.e. OIH), while Dcc heterozygous mice did not develop OIH. In addition, Dcc heterozygous mice had substantially reduced tolerance to morphine after several days of treatment and developed moderately less physical dependence on morphine than their wild-type littermates (Figure 4).
