Opioid-induced hyperalgesia: is it a clinically relevant phenomenon? Critical appraisal of the literature.

Abstract

Opioid-induced hyperalgesia (OIH) is a paradoxical effect of opioids that is not consensually recognized in clinical settings. We conducted a revision of clinical studies that show direct and indirect evidence of OIH. We discuss patient and drug-centered factors of variability in OIH manifestations and how the strategies to counter OIH, which include opioid switching, reduction in opioid dose and addition of adjuvant medication, rely on mechanisms suggesting the µ-opioid receptor (MOR) signals through opposite co-active pathways. We further discuss how recent findings on the cellular mechanisms involved in OIH, in addition to the neurobiology of MOR, including the growing information on the functional role of alternative splicing and heteromerization, may justify observable degrees of opioidergic dysregulation leading to mild hyperalgesia to full-scale OIH "disease". These findings call for a new perspective and awareness of OIH from a clinical point of view.