Fig. 5. Schematic view of the proposed opposing effects of opiates on nociception. Inflammatory processes induce pain sensitization (hyperalgesia) by activation of an NMDA-dependent sensitization loop. 1,2Opiates would activate not only pain inhibitory systems (eliciting analgesia) but also pain facilitatory systems (eliciting hyperalgesia). 18–21,24The latter would also act through the glutamatergic NMDA receptors. 1,18–20It was suggested that the interaction between μ-opioid and NMDA receptors results from increased protein kinase C γ activity. 50,51This hypothetical diagram would explain fentanyl enhancement of pain sensitization induced by carrageenan. NMDA-R =N -methyl-d-aspartate receptor; μ opiate-R =μ opiate receptor; PKCγ= protein kinase C γ.