This article is part of the supplement: 17th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access Meeting abstract

Efficacy of systemic HS-198, an analogue of oxymorphone, on cancer pain-related behaviour in mice

Muhammad F Asim1, Catalina R Bohotin1, Cristina E Constantin2, Helmut Schmidhammer1, Michaela Kress2 and Mariana Spetea1*

Author Affiliations

1 Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria

2 Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, 6020 Innsbruck, Austria

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BMC Pharmacology 2011, 11(Suppl 2):A4 doi:10.1186/1471-2210-11-S2-A4


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2210/11/S2/A4


Published:5 September 2011

© 2011 Asim et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Cancer pain is a significant clinical problem being one of the first symptoms of disease with 75–90% of the patients experiencing chronic pain syndromes in advanced stages [1]. The management of cancer pain is mainly based on the use of opioid drugs; however their clinical use is limited by high incidence of adverse effects. There is a continued search for highly efficacious opioid analgesics with reduced complications and improved patient compliance. An analogue of the clinically used oxymorphone, 5-methyl-substituted 14-O-methyloxymorphone (HS-198), is a selective μ opioid agonist and a potent antinociceptive agent in animal models of nociceptive and inflammatory pain, while exhibiting a favourable dissociation between analgesia and the occurrence of side effects [2]. We report data on efficacy of this opioid agonist after subcutaneous administration (s.c.) in a murine model of cancer pain. The opioid receptor-mechanistic basis of the antinociceptive action was also investigated.

Methods

Cancer pain was induced in C57BL/6J mice by s.c. implantation of lung carcinoma cells, in the plantar and dorsal side of the right hindpaw [3]. Mechanical sensitivity was determined using von Frey monofilaments. Heat sensitivity was assessed using the Hargreaves test. In vitro biological activities were evaluated using binding and functional assays.

Results

On day 9 post-inoculation, s.c. HS-198 produced a dose-dependent inhibition with significant effects in attenuating cancer pain-related behaviour (thermal and mechanical hypersensitivity) on the tumour side. Pre-treatment with the opioid receptor antagonist naloxone reversed the antinociceptive effects induced by HS-198 in mice with cancer-induced pain. In vitro, HS-198 showed high affinity and selectivity for both mouse and rat μ opioid receptors, and it displayed potent μ-agonism through inhibition of G proteins.

Conclusions

Systemic s.c. administration of the μ opioid receptor agonist HS-198 induces potent antinociceptive effects in mice with cancer pain via opioid receptor-specific mechanisms.

Acknowledgements

Supported by the Austrian Science Fund (FWF: TRP 19-B18).

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