Abstract
Peripheral analgesic effects of opioids are pronounced under inflammatory conditions, e.g., arthritis; however, little is known about adaptive changes of μ opioid receptor binding and G protein coupling in the peripheral versus central nervous system. The present study investigated the effects of inflammation on μ opioid receptor (MOP receptor) binding and G protein coupling of supraspinal, spinal, and peripheral MOP receptors. In addition, MOP receptors were identified in immunohistochemical experiments in dorsal root ganglia (DRG) of inflamed and noninflamed rats. The number of MOP receptor binding sites decreased from hypothalamus (HT) > spinal cord (SC) > DRG. Unilateral Freund's complete adjuvant inflammation of one hindpaw induced a significant up-regulation of MOP receptor sites only in DRG but not in HT or SC. This up-regulation was time-dependent, restricted to the inflamed side, and showed a peak at 24 h. The full-agonist [d-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAMGO) induced MOP receptor G protein coupling with decreasing efficacies (Emax) from HT > SC > DRG. Inflammation resulted in significant increases in MOP receptor G protein coupling only in membranes of DRG, but not in HT, SC, or DRG on the contralateral side of inflammation. This suggests that changes in MOP receptor levels are not related to systemically released mediators. These findings show that inflammation causes changes in MOP receptor binding and G protein coupling after DAMGO stimulation selectively in primary afferent neurons but did not cause any adaptive changes of MOP receptor in HT or SC.
Footnotes
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This work was supported by “Klinische Forschergruppe Grant from the Deutsche Forschungsgemeinschaft (DFG) KFO 100/1, International Anesthesia Research Society, and Graduiertenkolleg 276/2: Signalerkennung und-umsetzung”.
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DOI: 10.1124/jpet.103.057257.
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ABBREVIATIONS: CNS, central nervous system; MOP, μ opioid receptor; DRG, dorsal root ganglion; FCA, Freund's complete adjuvant; HT, hypothalamus; SC, spinal cord, spinal cord; GTPγS, guanosine-5′-O-(γ-thio)-triphosphate; DAMGO, [d-Ala2,N-MePhe4,Gly5-ol]enkephalin; ANOVA, analysis of variance.
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↵1 These authors contributed equally to this work.
- Received July 22, 2003.
- Accepted October 14, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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