Egr3, in the Prefrontal Cortex, Mediates Oxycodone-Induced Pain Relief
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Chronic pain is a debilitating and distressing condition with implications extending beyond the physical state of pain like anxiety, depression and cognitive appraisal. Chronic pain can cause neurobiological adaptations in different brain regions involved with sensory and affective pain processing. Pain assessment by patients suffering from chronic pain plays a role in the response to aversive pain and can reinforce behaviors that result in pain relief. Opioids, while effective for treatment of chronic pain, may lead to long-lasting neuroadaptations in the mesolimbic dopamine system or the “reward” circuitry. Long term use or misuse of opioids can lead to negative side effects such as dependence and addiction. Studies looking into the neurobiology of pain and addiction are of paramount importance as the intersection at which opioids can relieve pain and implications with substance abuse is poorly understood.Here we investigate the prefrontal cortex (PFC), an overlapping region for pain and reward mechanisms. Using an animal model of chronic inflammatory pain and whole-cell transcriptional profiling we hypothesized that pain in combination with oxycodone treatment will result in unique transcriptional signatures in the PFC when compared to pain or oxycodone alone. This transcriptional landscape will provide greater resolution on how pain and prescription opioids alter the PFC and potential cellular intermediates for effective pain management. We identified the transcription factor Egr3 as a possible target of pain processing based on RNA sequencing hits altered during oxycodone treatment in absence of pain. We hypothesized that Egr3, altered under the influence of oxycodone will modulate the degree of pain processing by opioids. We observed that Egr3 over-expression potentiated mechanical pain relief with oxycodone and Egr3 inhibition attenuated mechanical pain relief with oxycodone. Taken together, this demonstrates the importance of Egr3 in mediating sensory pain processing.