Evidence for the induction of analgesic cross-tolerance between opioid and apelin/APJ systems in male rats
BACKGROUND: 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.
METHODS: 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 (3µg/rat) or morphine (15µg/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 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.
CONCLUSION: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of studies on alcohol and drugs - (2024) vom: 22. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abbasloo, Elham [VerfasserIn] |
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Date Revised 23.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.15288/jsad.23-00377 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370073215 |
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| 100 | 1 | |a Abbasloo, Elham |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evidence for the induction of analgesic cross-tolerance between opioid and apelin/APJ systems in male rats |
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| 500 | |a Date Revised 23.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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 (3µg/rat) or morphine (15µg/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 | ||
| 520 | |a RESULTS: The data indicated that chronic apelin or morphine 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 | ||
| 520 | |a CONCLUSION: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Analgesia | |
| 650 | 4 | |a Apelin | |
| 650 | 4 | |a Cross-Tolerance | |
| 650 | 4 | |a Morphine | |
| 650 | 4 | |a Rats | |
| 700 | 1 | |a Esmaeili-Mahani, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Kobeissy, Firas |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Theresa Currier |e verfasserin |4 aut | |
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