NMDA receptor and NOS in morphine tolerance in mice with bone cancer

Abstract

To set up a mouse model with bone cancer to simulate the morphine tolerance and explore its mechanism. Forty C57BL/6 male mice were divided into 4 groups: Group 1 and Group 2 were firstly set up as bone cancer pain models. Morphine (10 mg/kg) was sequentially administered subcutaneously twice daily in Group 1 and normal saline was administered in Group 2 as the control group. Similar to Group 1 and Group 2, morphine (10 mg/kg) was administered subcutaneously twice daily in Group 3 and normal saline was administered in Group 4 as the control group. To set up morphine tolerance model, we injected morphine continuously for 7 days. From Day 1 to Day 7 after the morphine injection, we measured the mice hind paw withdrawal threshold in the von Frey hair test every other day. NMDA receptor 1 (NMDA1) and nitric oxide synthase (NOS) were measured on Day 7 after the morphine injection. The mice hind paw withdrawal threshold in the von Frey hair test in Group 1 increased on Day 1,3, and 5 after the morphine injection compared with the paw withdrawal threshold in Group 2 and had the same threshold as Group 2 on Day 7. The mice hind paw withdrawal threshold in the von Frey hair test in Group 3 increased on Day 1,3, and 5 after the morphine injection compared with the paw withdrawal threshold in Group 4 and had the same threshold as Group 4 on Day 7. The grey scales and integral optical density (IOD) of NMDAR1 and the level of NOS in the spinal dorsal horn were higher in Group 1, Group 2, and Group 3 compared with those in Group 4 (P<0.05 or P<0.01), and the grey scales and IOD of NMDAR1 in Group 2 was higher than that in Group 1 (P<0.05). NMDA receptors and NOS may play important roles in morphine tolerance in mice with bone cancer pain.