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Papers of the Week

Papers: 3 Jun 2023 - 9 Jun 2023

Basic Science

Animal Studies, Genetics, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development

Neuropathic Pain

2023 Jun 08

Nat Neurosci


Editor's Pick

Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.


Pryce KD, Serafini RA, Ramakrishnan A, Nicolais A, Giosan IM, Polizu C, Torres-Berrío A, Vuppala S, Kronman H, Ruiz A, Gaspari S, Peña CJ, Sakloth F, Mitsi V, van Duzer J, Mazitschek R, Jarpe M, Shen L, Nestler EJ, Zachariou V


The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. We developed a mouse model of oxycodone exposure and subsequent withdrawal in the presence or absence of chronic neuropathic pain. Oxycodone withdrawal alone triggered robust gene expression adaptations in the nucleus accumbens, medial prefrontal cortex and ventral tegmental area, with numerous genes and pathways selectively affected by oxycodone withdrawal in mice with peripheral nerve injury. Pathway analysis predicted that histone deacetylase (HDAC) 1 is a top upstream regulator in opioid withdrawal in nucleus accumbens and medial prefrontal cortex. The novel HDAC1/HDAC2 inhibitor, Regenacy Brain Class I HDAC Inhibitor (RBC1HI), attenuated behavioral manifestations of oxycodone withdrawal, especially in mice with neuropathic pain. These findings suggest that inhibition of HDAC1/HDAC2 may provide an avenue for patients with chronic pain who are dependent on opioids to transition to non-opioid analgesics.