Oxycodone-Induced Analgesic Effects in a Bone Cancer Pain Model in Mice

Abstract

The femur bone cancer pain model was developed by implanting mouse osteolytic tumor cells (NCTC 2472) into the intramedulla of the femur in C3H/HeN mice. In vivo imaging analysis revealed that the implanted tumor cells grew progressively over 14 days. Associated with the tumor growth, guarding behavior, which was an indication of ongoing pain, time-dependently increased. Limb use abnormality and allodynia, which were indications of ambulatory and neuropathic pain, respectively, also appeared. The analgesic effects of oxycodone and other opioids, such as morphine and fentanyl, were evaluated at 14 days when all pain-related behaviors clearly appeared. Oxycodone (2–20 mg/kg, s.c.), morphine (10–50 mg/kg, s.c.) and fentanyl (0.05–0.2 mg/kg, s.c.) significantly reduced guarding behavior. Oxycodone (5–20 mg/kg, s.c.) and fentanyl (0.1 and 0.2 mg/kg, s.c.) significantly reversed limb use abnormality, but morphine (5–50 mg/kg, s.c.) did not. Moreover, oxycodone (5–20 mg/kg, s.c.) dose-dependently reversed allodynia without affecting the sham-treated mice. Morphine (50 mg/kg, s.c.) and fentanyl (0.075–0.2 mg/kg, s.c.) also reversed allodynia, but morphine (50 mg/kg, s.c.) tended to affect and fentanyl (0.1 and 0.2 mg/kg, s.c.) affected the withdrawal threshold in sham-treated mice. These results suggested that oxycodone relieved not only ongoing pain, but also ambulatory and neuropathic pain, and that the analgesic profile of oxycodone could be different from that of either morphine or fentanyl.

Phosphoproteomic profiling of oxycodone‑treated spinal cord of rats with cancer‑induced bone pain

“…The preliminary experiments demonstrated that the onset time of oXY using the systemic administration route was 15 min, with peak efficacy after 30 min and efficacy lasting for 2-4 h (Fig. 2B), which was consistent with the results of previous studies (7,28,36,37). as shown in Fig.…”

“…The administration of saline (0.9%) and oXY hydrochloride injection (oxynorm; 10 mg/ml; napp Pharmaceuticals, ltd.) was randomized (n=21). oXY was diluted to 0.5 mg/ml with 0.9% saline and intraperitoneally injected at a dose of 2.5 mg/kg twice daily for 5 consecutive days from the 8th day after the injection of tumor cells to establish the ciBP model, as described previously (7,17,28,29). Saline was used in the control group.…”

Treatment Methods for Pain due to Bone Metastases

“…Opioidler, kemik metastazına bağlı ağrının medikal tedavisinde temel taşlardır. Preklinik araştırmalar farklı opioidler için etkinliğin değişken olabileceğini göstermekle birlikte (14), klinik kullanımda kemik metastazlarının ağrı tedavisinde daha üstün etkinlik gösteren bir opioid tanımlanamamıştır. Bazı opioidler hasta için diğer opioidlerden daha fazla analjezi sağlayabilir ve bunu belirlemenin tek yolu "deneme ve yanılma" dır.…”

Use of Animal Models in Understanding Cancer-induced Bone Pain

“… Selected pharmacological interventions with positive effects in animal models of CIBP: Trk inhibitor (ARRY-470); 79 BDNF siRNA; 82 P2X 3 antagonist (AF-353); 138 TRPV1 antagonist (JNJ-17203212); 125 IL-1 receptor antagonist (anakinra); 103 anti-MCP-1 antibody; 114 anti-CX3CR1 antibody; 110 , 111 anti-TNFα antibody (etanercept); 27 anti-NGF antibody; 75 , 77 sulfasalzine; 87 thalidomide; 105 gabapentin; 179 opioids (morphine, oxycodone); 180 , 181 alendronate; 177 cisplatin + 89 SR; 182 anti-RANKL antibody (denosumab); 183 Cox-2 inhibitor (MF tricyclic); 20 zoledronic acid; 176 p38 MAPK inhibitor (SB203580); 184 osteoprotegerin; 41 , 42 CB2 agonist (JWH015); 101 ibandronate; 44 , 45 risedronate; 44 , 46 anti-PTHrP antibody; 56 cathepsin K inhibitor; 178 TGFβ type I receptor kinase inhibitor (LY2109761); 57 and chemotherapeutics. Trk inhibitor, tropomyosin receptor kinase inhibitor; BDNF siRNA, brain-derived neurotrophic factor small interfering RNA; P2X 3 antagonist, P2X purinoceptor 3 antagonist; TRPV1 antagonist, transient receptor potential vanilloid type 1 antagonist; IL-1 receptor antagonist, interleukin-1 receptor antagonist; anti-MCP-1 antibody, anti-monocyte chemoattractant protein-1 antibody; anti-CX3CR1 antibody, anti-fractalkine receptor antibody; anti-TNFα antibody, antitumor necrosis factor-α antibody; anti-NGF antibody, anti-nerve growth factor antibody; anti-RANKL antibody, anti-receptor activator of nuclear factor κB ligand antibody; CB2 agonist, cannabinoid receptor 2 agonist; anti-PTHrP antibody, anti-parathyroid hormone related protein antibody.…”