Interleukin-1 beta contributes to the upregulation of kappa opioid receptor mrna in dorsal root ganglia in response to peripheral inflammation

Abstract

During local painful inflammation, axonal transport of opioid receptors from dorsal root ganglia toward the periphery is increased, associated with a higher receptor density and enhanced efficacy of opioid analgesics at the injured site. To examine whether this increase is related to transcription, mRNA of the kappa opioid receptor in lumbar dorsal root ganglia was quantified by real time light cycler polymerase chain reaction. In dorsal root ganglia of naive rats, kappa opioid receptor mRNA expression was three-fold higher than previously shown for delta opioid receptor and two times lower than mu opioid receptor mRNA, respectively. After induction of unilateral paw inflammation by Freund’s complete adjuvant, kappa opioid receptor mRNA was significantly upregulated with a peak at 12 h in ipsilateral dorsal root ganglia. This effect could be mimicked by intraplantar injection of the proinflammatory cytokine interleukin-1 beta. Kappa opioid receptor mRNA upregulation lasted longer in interleukin-1 beta–treated rats compared with Freund’s complete adjuvant–treated rats. Furthermore, a significant increase in kappa opioid receptor positive neurons was detected by immunohistochemistry 24 h after local injection of Freund’s complete adjuvant or interleukin-1 beta. In Freund’s complete adjuvant–induced inflammation, kappa opioid receptor upregulation was blocked by treatment with interleukin-1 receptor antagonist without changing the leukocyte infiltration in the paw. In conclusion, kappa opioid receptor mRNA and protein in dorsal root ganglia are upregulated in response to peripheral inflammation. This effect can be mimicked by a single local injection of interleukin-1 beta, and Freund’s complete adjuvant–induced upregulation in kappa opioid receptor mRNA and protein can be prevented by treatment with interleukin-1 receptor antagonist. These data suggest that the peripheral production of the proinflammatory cytokine interleukin-1 beta is a specific inducer of kappa opioid receptor expression in the dorsal root ganglia.