Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking induced by chronic inflammatory pain
Autor: | Alain Beaudet, Catherine M. Cahill, Brian Collier, Brigitte L. Kieffer, Anne Morinville |
---|---|
Rok vydání: | 2004 |
Předmět: |
Male
medicine.medical_specialty Freund's Adjuvant Central nervous system Receptors Opioid mu Pain Stimulation Inflammation Functional Laterality δ-opioid receptor Mice Receptors Opioid delta Internal medicine Animals Medicine Receptor Endogenous opioid Mice Knockout business.industry Cell Membrane Dendrites Spinal cord Immunohistochemistry Up-Regulation Mice Inbred C57BL Posterior Horn Cells Disease Models Animal Microscopy Electron Protein Transport Anesthesiology and Pain Medicine medicine.anatomical_structure Endocrinology Neurology Chronic Disease Immunology Female Neurology (clinical) medicine.symptom μ-opioid receptor business |
Zdroj: | Morinville, A; Cahill, CM; Kieffer, B; Collier, B; & Beaudet, A. (2004). Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking induced by chronic inflammatory pain. Pain, 109(3), 266-273. doi: 10.1016/j.pain.2004.01.011. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/47p2m3mm |
ISSN: | 0304-3959 |
Popis: | Previous studies from our laboratory have demonstrated that both chronic inflammatory pain, induced by intraplantar injection of complete Freund's adjuvant (CFA), and prolonged (48 h) stimulation of mu-opioid receptors (muOR) by systemic administration of a variety of selective agonists, resulted in enhanced plasma membrane targeting of delta-opioid receptors (deltaOR) in neurons of the dorsal spinal cord. To determine whether deltaOR trafficking induced by chronic inflammation was dependent on the activation of muOR, we investigated by immunogold cytochemistry the effects of intraplantar CFA injection on the plasma membrane density of deltaOR in muOR knockout (KO) mice. In untreated wild-type (WT) mice, only a small proportion of deltaOR was associated with neuronal plasma membranes in the dorsal horn of the spinal cord. The CFA-induced inflammation produced a significantly higher ratio of plasma membrane to intracellular receptors, as well as a 75% increase in the membrane density of immunoreactive deltaOR, in dendrites of the ipsilateral dorsal horn as compared to untreated mice. This increase in the membrane density of deltaOR was likely due to a recruitment of receptors from intracellular stores since no difference in the overall deltaOR immunolabeling density was evident between CFA-treated and untreated mice. Most importantly, the CFA-induced changes in deltaOR plasma membrane insertion seen in WT animals were not present in the spinal cord of muOR KO mice. These results demonstrate that the integrity of muOR is necessary for CFA-induced changes in deltaOR trafficking to occur and suggest that these changes could be elicited by stimulation of muOR by endogenous opioids released in response to chronic inflammatory pain. |
Databáze: | OpenAIRE |
Externí odkaz: |