Rapid upregulation of μ opioid receptor mrna in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction

Abstract

S.c. painful inflammation leads to an increase in axonal transport of opioid receptors from dorsal root ganglia (DRG) toward the periphery, thus causing a higher receptor density and enhanced opioid analgesia at the injured site. To examine whether this increase is related to transcription, the mRNA of Δ- (DOR) and μ-opioid receptor (MOR) in lumbar DRG was quantified by real time Light Cycler polymerase chain reaction (LC-PCR), and correlated to ligand binding in DRG and sciatic nerve. In normal DRG, DOR mRNA was seven times less abundantly expressed than MOR mRNA. After induction of unilateral paw inflammation, mRNA content for DOR remained unchanged, but a bi-phasic upregulation for MOR mRNA with an early peak at 1–2 h and a late increase at 96 h was found in ipsilateral DRG. As no changes were observed in DRG of the non-inflamed side, this effect was apparently not systemically mediated. A significant increase in binding of the MOR ligand DAMGO was detected after 24 h in DRG, and after early and late ligation in the sciatic nerve, indicating an enhanced axonal transport of MOR in response to inflammation. The early increase in MOR mRNA could be completely prevented by local anesthetic blockade of neuronal conduction in sciatic nerve. These data suggest that mRNA of the two opioid receptors DOR and MOR is differentially regulated in DRG during peripheral painful inflammation. The apparently increased axonal transport of MOR in response to this inflammation is preceded by upregulated mRNA-transcription, which is dependent on neuronal electrical activity.