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Biphalin preferentially recruits peripheral opioid receptors to facilitate analgesia in a mouse model of cancer pain - A comparison with morphine

Lesniak, Anna and Bochynska-Czyz, Marta and Sacharczuk, Mariusz and Benyhe, Sándor and Misicka, Aleksandra (2016) Biphalin preferentially recruits peripheral opioid receptors to facilitate analgesia in a mouse model of cancer pain - A comparison with morphine. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 89. pp. 39-49. ISSN 0928-0987

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Abstract

The search for new drugs for cancer pain management has been a long-standing goal in basic and clinical research. Classical opioid drugs exert their primary antinociceptive effect upon activating opioid receptors located in the central nervous system. A substantial body of evidence points to the relevance of peripheral opioid receptors as potential targets for cancer pain treatment. Peptides showing limited blood-brain-barrier permeability promote peripheral analgesia in many pain models. In the present study we examined the peripheral and central analgesic effect of intravenously administered biphalin - a dimeric opioid peptide in a mouse skin cancer pain model, developed by an intraplantar inoculation of B16F0 melanoma cells. The effect of biphalin was compared with morphine - a golden standard in cancer pain management. Biphalin produced profound, dose-dependent and naloxone sensitive spinal analgesia. Additionally, the effect in the tumor-bearing paw was largely mediated by peripheral opioid receptors, as it was readily attenuated by the blood-brain-barrier-restricted opioid receptor antagonist - naloxone methiodide. On the contrary, morphine facilitated its analgesic effect primarily by activating spinal opioid receptors. Both drugs induced tolerance in B16F0 - implanted paws after chronic treatment, however biphalin as opposed to morphine, showed little decrease in its activity at the spinal level. Our results indicate that biphalin may be considered a future alternative drug in cancer pain treatment due to an enhanced local analgesic activity as well as lower tolerance liability compared with morphine. (C) 2016 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: RAT; ANTINOCICEPTION; knee arthroscopy; INFLAMMATORY PAIN; INDUCED HYPERALGESIA; TUMOR-GROWTH; INTRAARTICULAR MORPHINE; STRESS-INDUCED ANALGESIA; DIMERIC ENKEPHALIN ANALOG; CENTRAL-NERVOUS-SYSTEM; TOLERANCE; MOUSE MODEL; Peripheral analgesia; cancer pain; biphalin
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia
R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 01 Mar 2017 09:37
Last Modified: 01 Mar 2017 09:37
URI: http://real.mtak.hu/id/eprint/49743

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