Peripheral antinociceptive effects of a bifunctional μ and δ opioid receptor ligand in rat model of inflammatory bladder pain
Copyright © 2021 Elsevier Ltd. All rights reserved..
There is a need to develop a novel analgesic for pain associated with interstitial cystitis/painful bladder syndrome (IC/PBS). The use of the conventional μ-opioid receptor agonists to manage IC/PBS pain is controversial due to adverse CNS effects. These effects are attenuated in benzylideneoxymorphone (BOM), a low-efficacy μ-opioid receptor agonist/δ-opioid receptor antagonist that attenuates thermal pain and is devoid of reinforcing effects. We hypothesize that BOM will inhibit bladder pain by attenuating responses of urinary bladder distension (UBD)-sensitive afferent fibers. Therefore, the effect of BOM was tested on responses of UBD-sensitive afferent fibers in L6 dorsal root from inflamed and non-inflamed bladder of rats. Immunohistochemical (IHC) examination reveals that following the induction of inflammation there were significant high expressions of μ, δ, and μ-δ heteromer receptors in DRG. BOM dose-dependently (1-10 mg/kg, i.v) attenuated mechanotransduction properties of these afferent fibers from inflamed but not from non-inflamed rats. In behavioral model of bladder pain, BOM significantly attenuated visceromotor responses (VMRs) to UBD only in inflamed group of rats when injected either systemically (10 mg/kg, i.v.) or locally into the bladder (0.1 ml of 10 mg/ml). Furthermore, oxymorphone (OXM), a high-efficacy μ-opioid receptor agonist, attenuated responses of mechanosensitive bladder afferent fibers and VMRs to UBD. Naloxone (10 mg/kg, i.v.) significantly reversed the inhibitory effects of BOM and OXM on responses of bladder afferent fibers and VMRs suggesting μ-opioid receptor-related analgesic effects of these compounds. The results reveal that a low-efficacy, bifunctional opioid-based compound can produce analgesia by attenuating mechanotransduction functions of afferent fibers innervating the urinary bladder.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:196 |
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| Enthalten in: |
Neuropharmacology - 196(2021) vom: 15. Sept., Seite 108701 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Terashvili, Maia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.02.2022 Date Revised 16.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neuropharm.2021.108701 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM328017329 |
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| 245 | 1 | 0 | |a Peripheral antinociceptive effects of a bifunctional μ and δ opioid receptor ligand in rat model of inflammatory bladder pain |
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| 500 | |a Date Revised 16.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a There is a need to develop a novel analgesic for pain associated with interstitial cystitis/painful bladder syndrome (IC/PBS). The use of the conventional μ-opioid receptor agonists to manage IC/PBS pain is controversial due to adverse CNS effects. These effects are attenuated in benzylideneoxymorphone (BOM), a low-efficacy μ-opioid receptor agonist/δ-opioid receptor antagonist that attenuates thermal pain and is devoid of reinforcing effects. We hypothesize that BOM will inhibit bladder pain by attenuating responses of urinary bladder distension (UBD)-sensitive afferent fibers. Therefore, the effect of BOM was tested on responses of UBD-sensitive afferent fibers in L6 dorsal root from inflamed and non-inflamed bladder of rats. Immunohistochemical (IHC) examination reveals that following the induction of inflammation there were significant high expressions of μ, δ, and μ-δ heteromer receptors in DRG. BOM dose-dependently (1-10 mg/kg, i.v) attenuated mechanotransduction properties of these afferent fibers from inflamed but not from non-inflamed rats. In behavioral model of bladder pain, BOM significantly attenuated visceromotor responses (VMRs) to UBD only in inflamed group of rats when injected either systemically (10 mg/kg, i.v.) or locally into the bladder (0.1 ml of 10 mg/ml). Furthermore, oxymorphone (OXM), a high-efficacy μ-opioid receptor agonist, attenuated responses of mechanosensitive bladder afferent fibers and VMRs to UBD. Naloxone (10 mg/kg, i.v.) significantly reversed the inhibitory effects of BOM and OXM on responses of bladder afferent fibers and VMRs suggesting μ-opioid receptor-related analgesic effects of these compounds. The results reveal that a low-efficacy, bifunctional opioid-based compound can produce analgesia by attenuating mechanotransduction functions of afferent fibers innervating the urinary bladder | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Analgesic | |
| 650 | 4 | |a Bladder afferents | |
| 650 | 4 | |a Bladder pain | |
| 650 | 4 | |a Cystitis | |
| 650 | 4 | |a Opioids | |
| 650 | 7 | |a Analgesics |2 NLM | |
| 650 | 7 | |a Benzylidene Compounds |2 NLM | |
| 650 | 7 | |a Narcotic Antagonists |2 NLM | |
| 650 | 7 | |a Receptors, Opioid, delta |2 NLM | |
| 650 | 7 | |a Receptors, Opioid, mu |2 NLM | |
| 650 | 7 | |a Naloxone |2 NLM | |
| 650 | 7 | |a 36B82AMQ7N |2 NLM | |
| 650 | 7 | |a Oxymorphone |2 NLM | |
| 650 | 7 | |a 9VXA968E0C |2 NLM | |
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| 700 | 1 | |a Palangmonthip, Watchareepohn |e verfasserin |4 aut | |
| 700 | 1 | |a Iczkowski, Kenneth A |e verfasserin |4 aut | |
| 700 | 1 | |a Sanvanson, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Medda, Bidyut K |e verfasserin |4 aut | |
| 700 | 1 | |a Banerjee, Banani |e verfasserin |4 aut | |
| 700 | 1 | |a Cunningham, Christopher W |e verfasserin |4 aut | |
| 700 | 1 | |a Sengupta, Jyoti N |e verfasserin |4 aut | |
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