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Enhanced delta-opioid receptor-mediated antinociception in mu-opioid receptor-deficient mice
1Department of Oral and Craniofacial Biological Sciences, University of Maryland Dental School, Room 5E-08, 666 West Baltimore Street, Baltimore, MD 21201, USA.
Abstract:
Inflammatory hyperalgesia was induced in wild-type, heterozygous and mu-opioid receptor knockout mice after an intraplantar injection of complete Freund's adjuvant. micro-Opioid receptor knockout mice exhibited faster recovery from hyperalgesia as compared to heterozygous (P<0.05) and wild-type (P<0.01) mice. Naloxone restored hyperalgesia in all genotypes. Naltrindole (delta-opioid receptor-selective antagonist) partially restored the hyperalgesia only in mu-opioid receptor knockout mice (P<0.001). Nor-binaltorphimine (kappa-opioid receptor-selective antagonist) had no effect. The mu-opioid receptor-selective agonist, [D-Ala(2), MePhe(4),Gly-ol(5)]enkephalin (DAMGO), reduced the hyperalgesia in heterozygous and wild-type but not in mu-opioid receptor knockout mice while U69,593 ¿(+)-(5alpha,7alpha, 8beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4. 5]dec-8-yl]-benzeneacetamide, kappa-opioid receptor-selective¿ produced similar effects in all mice. The delta-opioid receptor-selective agonists, [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and deltorphin ([D-Ala(2)]deltrophin-II), produced significantly greater antihyperalgesia in knockout mice (P<0.05). The findings suggest that mu-opioid receptors may be involved in the persistence of inflammatory hyperalgesia and that a delta-opioid receptor-mediated compensatory mechanism in the absence of the mu-opioid receptor is activated by persistent hyperalgesia.
Insights
Mice lacking mu-opioid receptors recovered faster from inflammatory hyperalgesia. This suggests mu-opioid receptors contribute to persistent pain, while delta-opioid receptors may compensate for their absence.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Inflammatory hyperalgesia is a common pain condition.
- Opioid receptors, particularly mu-opioid receptors, are known targets for pain relief.
- The specific roles of different opioid receptor subtypes in persistent inflammatory pain are not fully understood.
Purpose of the Study:
- To investigate the role of mu-opioid receptors in the development and resolution of inflammatory hyperalgesia.
- To explore potential compensatory mechanisms involving other opioid receptor subtypes.
Main Methods:
- Induction of inflammatory hyperalgesia in wild-type, heterozygous, and mu-opioid receptor knockout mice using complete Freund's adjuvant.
- Administration of opioid receptor antagonists (naloxone, naltrindole, nor-binaltorphimine) and agonists (DAMGO, U69,593, DPDPE, deltorphin).
- Assessment of recovery from hyperalgesia across different genotypes and treatments.
Main Results:
- Mu-opioid receptor knockout mice showed significantly faster recovery from hyperalgesia compared to wild-type and heterozygous mice.
- Naloxone (non-selective opioid antagonist) reversed hyperalgesia in all groups.
- Naltrindole (delta-opioid antagonist) partially reversed hyperalgesia specifically in knockout mice.
- Selective mu-opioid agonists reduced hyperalgesia in wild-type but not knockout mice.
- Selective delta-opioid agonists produced greater antihyperalgesic effects in knockout mice.
Conclusions:
- Mu-opioid receptors appear to play a role in the persistence of inflammatory hyperalgesia.
- A compensatory mechanism involving delta-opioid receptors is activated in the absence of mu-opioid receptors during persistent hyperalgesia.