Novel Endomorphin Analogs Are More Potent and Longer-Lasting Analgesics in Neuropathic, Inflammatory, Postoperative, and Visceral Pain Relative to Morphine

JOURNAL OF PAIN

卷:18

Article

Feehan, Amy K.¹  Morgenweck, Jenny²  Zhang, Xing³  Amgott-Kwan, Ariel T.¹  Zadina, James E.^1,3,4,5 

[1] Tulane Brain Inst, New Orleans, LA USA

[2] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

[3] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA

[4] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA

[5] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA USA

关键词: Pre-clinical pain models;    neuropathic pain;    inflammatory pain;    postoperative pain;    visceral pain;    morphine;    endomorphin analogs;   

DOI  :  10.1016/j.jpain.2017.08.007

来源: Elsevier

【 摘 要 】

Activation of the mu-opioid receptor provides the gold standard for pain relief, but most opioids used clinically have adverse effects that have contributed to an epidemic of overdose deaths. We recently characterized mu-opioid receptor selective endomorphin (EM) analogs that provide potent antinociception with reduction or absence of a number of side effects of traditionally prescribed opioids including abuse liability, respiratory depression, motor impairment, tolerance, and inflammation. The current study explores the effectiveness of these EM analogs relative to morphine in four major pain models by intrathecal as well as intravenous administration in male Sprague Dawley rats and subcutaneous administration in male CD-1 mice. In the spared nerve injury model of neuropathic pain, mechanical allodynia and mechanical hyperalgesia were assessed with von Frey and Randall-Selitto tests, respectively. In the paw incision model of postoperative pain, von Frey testing was used to assess mechanical allodynia and thermal hyperalgesia was evaluated with Hargreaves testing. In the Complete Freund's Adjuvant model of inflammatory pain, thermal hyperalgesia was assessed using Hargreaves testing. In CD-1 mice, visceral pain was assessed with the acetic acid writhing test. In all cases, EM analogs had equal or greater potency and longer duration of action relative to morphine. The data suggest that EM analogs, particularly analog 4 (ZH853), could provide effective therapy for a diverse spectrum of pain conditions with low risk of adverse side effects compared with currently used opioids such as morphine. Perspective: Novel EM analogs show equal or greater potency and effectiveness relative to morphine in multiple pain models. Together with substantially reduced side effects, including abuse liability, the compounds show promise for addressing the critical need for effective pain relief as well as reducing the opioid overdose epidemic. Published by Elsevier Inc. on behalf of the American Pain Society

【 授权许可】

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