Abstract
The role of opioid receptors located in the central nervous system (CNS) and peripheral nervous system in inflammatory pain is well established. In contrast, although it is has been shown that μ agonists can reduce other manifestations of inflammation, such as edema, the mechanism of action remains unclear. In this study, we have activated μ receptors located centrally, those located peripherally, and those located both centrally and peripherally and compared the effects on pain and edema using the rat carrageenan model of acute inflammation. Activation of μ receptors located only in the periphery, by administration of the peripheralized μ agonist [8-(3,3-diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic acid (DiPOA) or local administration of morphine, resulted in antihyperalgesia (30 mg/kg DiPOA, 83% inhibition; 100 μg/rat morphine, 75% inhibition) without affecting edema. In contrast, activation of both central and peripheral μ receptors using systemically administered morphine resulted in antihyperalgesia (1 mg/kg, 80% inhibition) and inhibition of edema (10 mg/kg, 54% inhibition). Finally, activation of only receptors located in the CNS, by central administration of DiPOA or systemic administration of morphine after block of only the peripheral μ receptors using q-naltrexone, resulted in a significant reduction in edema. Our findings confirm the role of peripheral μ receptors in the pathology of pain associated with acute inflammation and argue against the involvement of these receptors in edema formation. Furthermore, our data demonstrate that activation of μ receptors in the brain inhibits carrageenan-induced edema and suggest that the antiedematous effect of morphine is due to action at central receptors alone.
Footnotes
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.088351.
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ABBREVIATIONS: CNS, central nervous system; PNS, peripheral nervous system; DiPOA, [8-(3,3-diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic acid; FCA, Freund's complete adjuvant; i.pl., intraplantar; PWT, paw withdrawal threshold; PLSD, protected least significant difference.
- Received April 21, 2005.
- Accepted June 1, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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