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.

1.
Monory K, Greiner E, Sartania N, Sallai L, Pouille Y, Schmidhammer H, Hanoune J, Borsodi A: Opioid binding profiles of new hydrazone, oxyme, carbazone and semicarbazone derivatives of 14-alkoxymorphinans. Life Sci 1999;64:2011–2020.
2.
Peckham EM, Traynor JR: Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats. J Pharmacol Exp Ther 2006;316:1195–1201.
3.
Narita M, Nakamura A, Ozaki M, Imai S, Miyoshi K, Suzuki M, Suzuki T: Comparative pharmacological profiles of morphine and oxycodone under a neuropathic pain-like state in mice: evidence for less sensitivity to morphine. Neuropsychopharmacology 2008;33:1097–1112.
4.
Lemberg KK, Kontinen VK, Siiskonen AO, Viljakka KM, Yli-Kauhaluoma JT, Korpi ER, Kalso EA: Antinociception by spinal and systemic oxycodone: why does the route make a difference? In vitro and in vivo studies in rats. Anesthesiology 2006;105:801–812.
5.
Lemberg K, Kontinen VK, Viljakka K, Kylänlahti I, Yli-Kauhaluoma J, Kalso E: Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat. Anesth Analg 2006;102:1768–1774.
6.
Nozaki C, Saitoh A, Kamei J: Characterization of the antinociceptive effects of oxycodone in diabetic mice. Eur J Pharmacol 2006;535:145–151.
7.
Mercadante S, Arcuri E: Breakthrough pain in cancer patients: pathophysiology and treatment. Cancer Treat Rev 1998;24:425–432.
8.
Portenoy RK, Payne D, Jacobsen P: Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81:129–134.
9.
Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, Clohisy DR, Mantyh PW: Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci 1999;19:10886–10897.
10.
Becker R, Jakob D, Uhle EI, Riegel T, Bertalanffy H: The significance of intrathecal opioid therapy for the treatment of neuropathic cancer pain conditions. Stereotact Funct Neurosurg 2000;75:16–26.
11.
Peters CM, Ghilardi JR, Keyser CP, Kubota K, Lindsay TH, Lugar NM, Mach DB, Schwei MJ, Sevcik MA, Mantyh PW: Tumor-induced injury of primary afferent sensory nerve fivers in bone cancer pain. Exp Neurol 2005;193:85–100.
12.
Bercovitch M, Adunsky A: High dose controlled-release oxycodone in hospice care. J Pain Palliat Care Pharmacother 2006;20:33–39.
13.
Honore P, Lugar NM, Sabino MAC, Schwei MJ, Rogers SD, Mach DB, O’keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW: Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 2000;6:521–528.
14.
Luger NM, Sabino MA, Schwei MJ, Mach DB, Pomonis JD, Keyser CP, Rathbun M, Clohisy DR, Honore P, Yaksh TL, Mantyh PW: Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs inflammatory pain. Pain 2002;99:397–406.
15.
Vermeirsch H, Nuydens RM, Salmon PL, Meert TF: Bone cancer pain model in mice: evaluation of pain behavior, bone destruction and morphine sensitivity. Pharmacol Biochem Behav 2004;79:243–251.
16.
Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG, Jonas BM, Kubota K, Kuskowski MA, Boustany L, Shelton DL, Mantyh PW: Anti-NGF therapy profoundly reduces bone caner pain and the accompanying increase in markers of peripheral and central sensitization. Pain 2005;115:128–141.
17.
Gilchrist LS, Cain DM, Harding-Rose C, Kov AN, Wendelschafer-Crabb G, Kennedy WR, Simone DA: Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain. Brain Res 2005;1044:197–205.
18.
Arnér S, Meyerson BA: Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1998;33:11–23.
19.
Stanfa L, Dickenson A: Spinal opioid systems in inflammation. Inflamm Res 1995;44:231–241.
20.
Bridges D, Thompson SWN, Rice ASC: Mechanisms of neuropathic pain. Br J Anaesth 2001;87:12–26.
21.
El Mouedden M, Meert TF: Evaluation of pain-related behavior, bone destruction and effectiveness of fentanyl, sufentanil, and morphine in a murine model of cancer pain. Pharmacol Biochem Behav 2005;82:109–119.
22.
El Mouedden M, Meert TF: The impact of the opioids fentanyl and morphine on nociception and bone destruction in a murine model of bone caner pain. Pharmacol Biochem Behav 2007;87:30–40.
23.
Pan YX, Xu J, Bolan E, Moskowitz HS, Xu M, Pasternak GW: Identification of four novel exon 5 splice variants of the mouse mu-opioid receptor gene: functional consequences of C-terminal splicing. Mol Pharmacol 2005;68:866–875.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.