Evidence for the Induction of Analgesic Cross-Tolerance Between Opioid and Apelin/APJ Systems in Male Rats

被引:0
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作者
Abbasloo, Elham [1 ]
Esmaeili-mahani, Saeed [2 ]
Kobeissy, Firas [3 ,4 ]
Thomas, Theresa currier [5 ,6 ]
机构
[1] Kerman Univ Med Sci, Inst Basic & Clin Physiol Sci, Endocrinol & Metab Res Ctr, Kerman, Iran
[2] Shahid Bahonar Univ Kerman, Fac Sci, Dept Biol, Kerman, Iran
[3] Amer Univ Beirut, Fac Med, Dept Biochem & Mol Genet, Beirut, Lebanon
[4] Morehouse Sch Med, Neurosci Inst, Ctr Neurotrauma Multiom & Biomarkers CNMB, Dept Neurobiol, Atlanta, GA USA
[5] Univ Arizona, Coll Med Phoenix, Dept Child Hlth, Phoenix, AZ USA
[6] Phoenix Childrens Hosp, Barrow Neurol Inst, Phoenix, AZ USA
基金
美国国家卫生研究院;
关键词
RECEPTOR DOWN-REGULATION; ANTINOCICEPTIVE TOLERANCE; PERIAQUEDUCTAL GRAY; MORPHINE-TOLERANCE; MESSENGER-RNA; PROTEIN; APELIN-13; PAIN; DESENSITIZATION; EXPRESSION;
D O I
10.15288/jsad.23-00377
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
Objective: Opioids are potent pain relievers for managing severe pain. However, their effectiveness is hindered by tolerance, which causes the need for higher doses and leads to adverse effects. In a previous study, we found that prolonged use of apelin, similar to opioids, results in a tolerance to its analgesic effects. It remains unclear whether there is a cross-tolerance between morphine and apelin, meaning if the analgesic effects of one can reduce the effectiveness of the other. Method: The tail-flick test was used to assess the nociceptive threshold. All experiments were carried out on 63 male Wistar rats, which received intrathecal apelin (3 mu g/rat) or morphine (15 mu g/rat) for 7 days. To determine cross-tolerance between the analgesic effect of morphine and apelin, the analgesic property of apelin or morphine was assessed in chronic morphine- or apelin-treated groups, respectively. To determine the role of apelin and opioid receptors signaling on the development of analgesic cross-tolerance, F13-A and naloxone, as apelin and opioid receptor antagonists, were injected simultaneously with morphine or apelin. At the end of the tests, the expression levels of apelin and mu- opioid receptors were evaluated by western blotting. Results: The data indicated that chronic apelin or morphine use produced tolerance to the antinociceptive effects of each other. F13-A and naloxone could inhibit the induction of such cross-tolerance. The molecular data showed that there was a significant downregulation of apelin receptors in chronic morphine-treated rats and vice versa. Conclusions: Chronic administration of apelin or morphine induces analgesic cross-tolerance that may, in part, be mediated through receptor interactions and downregulation. The demonstrated efficacy of F13-A in these experiments highlights its potential as a novel target for improving pain management through the inhibition of the apelin/APJ signaling pathway, meriting further investigation. ( J. Stud. Alcohol Drugs, 85, 704-712, 2024)
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页码:704 / 712
页数:9
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