UC San Diego

Opioids are among the most widely used medication classes globally and are frequently prescribed in the treatment of pain conditions. Paradoxically, some individuals taking opioids might develop a condition of increased pain sensitivity referred to as opioid-induced hyperalgesia (OIH). Understanding the underlying biological mechanisms of OIH will improve treatment outcomes. Current proposed mechanisms of OIH include neuroplastic changes to the descending pain modulatory pathway between the midbrain periaqueductal gray, brainstem rostral ventromedial medulla, and spinal cord Dorsal Horn. In order to extend current knowledge of activity-dependent changes in the descending pain modulatory pathway in OIH, we used immunohistology techniques to examine the activity of three well-studied activity markers– Fos, NPAS4, and pERK1/2– in the ventrolateral periaqueductal gray in a mouse model of OIH. Furthermore, we evaluated changes in these markers as a result of persistent Formalin-evoked pain during OIH. It was found that basal Fos expression was reduced in OIH mice compared to controls, but this difference was abolished when assessing formalin-evoked activity. Together, these data support a model of reduced descending antinociceptive control from the vlPAG to the RVM that may enhance concomitant RVM-mediated pain facilitation in OIH.