Oxycodone‐induced gene expression adaptations in the brain reward center in a murine model of neuropathic pain

Abstract

Chronic neuropathic pain is a complex condition with complications beyond physical symptoms that include depression, anxiety, and cognitive issues. One in five patients suffering from chronic pain is prescribed an opiate drug such as oxycodone for pain relief. Long‐term use of oxycodone and other opiates for the treatment of chronic pain can lead to physical dependence and addiction. Recent studies from our group revealed that chronic neuropathic pain promotes several adaptations in the brain reward regions responsible for both the sensory and affective components associated with chronic pain (Descalzi et al., 2017, Sci. Signaling). Here, we are using Next Generation RNA‐sequencing to gain insight on the gene expression adaptations triggered by persistent exposure to oxycodone and to determine the impact of neuropathic pain in maladaptive plasticity to oxycodone. We employed the spared nerve injury model (SNI) of neuropathic pain in adult C57Bl/6 mice and assessed peripheral neuropathy symptoms (thermal hyperalgesia, mechanical allodynia) for ~9 weeks. Mice were then treated daily with oxycodone, for two weeks and gene expression was monitored three weeks after oxycodone withdrawal. Oxycodone treatment induced thermal hyperalgesia regardless of pain states, while withdrawal produced significant mechanical allodynia. We next monitored changes in gene expression for three brain regions implicated in the symptoms of chronic neuropathic pain: medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and the ventral tegmental area (VTA). Although oxycodone treatment promotes mostly unique transcriptome profile across brain regions, we observed similar downstream effectors and transcription factors to be affected in pain states when compared with non‐pain states. We are currently validating these genes using transgenic mouse lines to investigate their roles in potentiating oxycodone induced analgesia as well as physical dependence and addiction‐like behaviors. Understanding the gene adaptions in the brain after oxycodone treatment provides novel insight into the cellular machinery involved in maladaptive responses to drugs of abuse in the presence and absence of pain.Support or Funding Information5T32DA007135‐34, NIDA, R01 NS086444‐01, NINDS, and P01 DA008227, NIDAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.