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Objective:Opioid-induced hyperalgesia, a paradoxical increase in pain sensitivity associated with ongoing opioid use, may worsen the postoperative pain experience. This pilot study examined the effect of chronic opioid use on pain responses in patients undergoing a standardized dental surgery.Methods:Experimental and subjective pain responses were compared prior to and immediately following planned multiple tooth extractions between patients with chronic pain on opioid therapy (≥30 mg morphine equivalents/d) and opioid-naïve patients without chronic pain matched on sex, race, age, and degree of surgical trauma.Results:Preoperatively, chronic opioid users rated experimental pain as more severe and appreciated less central modulation of that pain than did opioid-naïve participants. Postoperatively, chronic opioid-using patients rated their pain as more severe during the first 48 hours and used almost twice as many postoperative analgesic doses during the first 72 hours as the opioid-naïve controls.Conclusion:These data suggest that patients with chronic pain taking opioids approach surgical interventions with heightened pain sensitivity and have a more severe postoperative pain experience, providing evidence that their complaints of postoperative pain should be taken seriously and managed appropriately.

The Switch/Sugar Non-Fermenting (SWI/SNF) nucleosome remodeling complexes play important roles in normal development and in the development of various cancers. Core subunits of the SWI/SNF complexes have been shown to have oncogenic roles in acute myeloid leukemia. However, the roles of the unique targeting subunits, including that of Arid2 and Arid1b, in AML leukemogenesis are not well understood. Here, we used conditional knockout mouse models to elucidate their role in MLL-AF9 leukemogenesis. We uncovered that Arid2 has dual roles; enhancing leukemogenesis when deleted during leukemia initiation and yet is required during leukemia maintenance. Whereas, deleting Arid1b in either phase promotes leukemogenesis. Our integrated analyses of transcriptomics and genomic binding data showed that, globally, Arid2 and Arid1b regulate largely distinct sets of genes at different disease stages, respectively, and in comparison, to each other. Amongst the most highly dysregulated transcription factors upon their loss, Arid2 and Arid1b converged on the regulation of Etv4/Etv5, albeit in an opposing manner while also regulating distinct TFs including Gata2,Tcf4, Six4, Irf4 and Hmgn3. Our data demonstrate the differential roles of SWI/SNF subunits in AML leukemogenesis and emphasize that cellular context and disease stage are key in determining their functions during this process.

Switch Sugar Non- Fermenting (SWI/SNF) nucleosome remodeling complexes are multi subunits complexes that utilize the energy from ATP to remodel chromatin, affecting cellular processes on chromatin including that of gene transcription. SWI/SNF complexes play important roles in normal development and differentiation as well as in oncogenesis. ARID1 proteins, ARID1A and ARID1B, are unique and mutually exclusive subunits of the canonical SWI/SNF complex BRG-1/BRM Associated Factor (BAF) complex. Arid1a is the most frequently mutated SWI/SNF subunit in cancers and plays a vital role in hematopoiesis. Arid1b is also frequently mutated in cancers, and its loss promotes Acute Myeloid Leukemia leukemogenesis. However, its role in normal hematopoiesis is not known.

The article presents letters to the editor referencing topics and responding to articles in previous issues, including "Hearing From Home," by Kirk Franklin, and features on Christian musicians Hawk Nelson and Neal Morse.