A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis

Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In some HS patients, mutations in the ankyrin promoter have been hypothesized to lead to decreased ankyrin mRNA synthesis. The ankyrin erythroid promoter is a member of the most common class of mammalian promoters which lack conserved TATA, initiator or other promoter cis elements and have high G+C content, functional Sp1 binding sites and multiple transcription initiation sites. We identified a novel ankyrin gene promoter mutation, a TG deletion adjacent to a transcription initiation site, in a patient with ankyrin-linked HS and analyzed its effects on ankyrin expression. In vitro, the mutant promoter directed decreased levels of gene expression, altered transcription initiation site utilization and exhibited defective binding of TATA-binding protein (TBP) and TFIID complex formation. In a transgenic mouse model, the mutant ankyrin promoter led to abnormalities in gene expression, including decreased expression of a reporter gene and altered transcription initiation site utilization. These data indicate that the mutation alters ankyrin gene transcription and contributes to the HS phenotype by decreasing ankyrin gene synthesis via disruption of TFIID complex interactions with the ankyrin core promoter. These studies support the model that in promoters that lack conserved cis elements, the TFIID complex directs preinitiation complex formation at specific sites in core promoter DNA and provide the first evidence that disruption of TBP binding and TFIID complex formation in this type of promoter leads to alterations in start site utilization, decreased gene expression and a disease phenotype in viv

American Society of Pain and Neuroscience Best Practice (ASPN) Guideline for the Treatment of Sacroiliac Disorders

Dawood Sayed,1 Timothy R Deer,2,3 Vinicius Tieppo Francio,1 Christopher M Lam,1 Kamil Sochacki,4 Nasir Hussain,5 Tristan E Weaver,5 Jay Karri,6,7 Vwaire Orhurhu,8,9 Natalie Holmes Strand,10 Jacqueline Soicher Weisbein,11 Jonathan M Hagedorn,12 Ryan S D’Souza,12 Ryan R Budwany,2 Ahish Chitneni,13 Kasra Amirdelfan,14 Michael J Dorsi,15 Dan TD Nguyen,16 Christopher Bovinet,17 Alaa Abd-Elsayed18 1Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 2Pain Services, Spine and Nerve Center of the Virginias, Charleston, WV, USA; 3Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USA; 4Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson, New Brunswick, NJ, USA; 5Anesthesiology, the Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Orthopedic Surgery, University of Maryland School of Medicine, Baltimore, MD, USA; 7Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 8Department of Anesthesiology, University of Pittsburgh Medical Center, Williamsport, PA, USA; 9Pain Medicine, MVM Health, East Stroudsburg, PA, USA; 10Anesthesiology and Pain Medicine, Mayo Clinic, Phoenix, AZ, USA; 11Interventional Pain Management, Napa Valley Orthopaedic Medical Group, Napa, CA, USA; 12Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 13Department of Rehabilitation & Regenerative Medicine, New York Presbyterian – Columbia & Cornell, New York, NY, USA; 14Director of Clinical Research, Boomerang Healthcare, Walnut Creek, CA, USA; 15Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA; 16Neuroradiology & Pain Solutions of Oklahoma, Edmond, OK, USA; 17The Spine Center of SE Georgia, Brunswick, GA, USA; 18Anesthesiology, University of Wisconsin, Madison, WI, USACorrespondence: Dawood Sayed, Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA, Tel +1 785-550-5800, Email [email protected]: Clinical management of sacroiliac disease has proven challenging from both diagnostic and therapeutic perspectives. Although it is widely regarded as a common source of low back pain, little consensus exists on the appropriate clinical management of sacroiliac joint pain and dysfunction. Understanding the biomechanics, innervation, and function of this complex load bearing joint is critical to formulating appropriate treatment algorithms for SI joint disorders. ASPN has developed this comprehensive practice guideline to serve as a foundational reference on the appropriate management of SI joint disorders utilizing the best available evidence and serve as a foundational guide for the treatment of adult patients in the United States and globally.Keywords: sacroiliac joint, sacroiliitis, chronic pain, best practices, radiofrequency ablation, sacroiliac joint fusio

American Society of Pain and Neuroscience Best Practice (ASPN) Guideline for the Treatment of Sacroiliac Disorders [Response to Letter]

Dawood Sayed,1 Timothy R Deer,2,3 Vinicius Tieppo Francio,1 Christopher M Lam,1 Kamil Sochacki,4 Nasir Hussain,5 Tristan E Weaver,5 Jay Karri,6,7 Vwaire Orhurhu,8,9 Natalie Holmes Strand,10 Jacqueline Soicher Weisbein,11 Jonathan M Hagedorn,12 Ryan S D’Souza,12 Ryan R Budwany,2 Ahish Chitneni,13 Kasra Amirdelfan,14 Michael J Dorsi,15 Dan TD Nguyen,16 Christopher Bovinet,17 Alaa Abd-Elsayed18 1Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 2Pain Services, Spine and Nerve Center of the Virginias, Charleston, WV, USA; 3Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USA; 4Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson, New Brunswick, NJ, USA; 5Anesthesiology, the Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Orthopedic Surgery, University of Maryland School of Medicine, Baltimore, MD, USA; 7Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 8Department of Anesthesiology, University of Pittsburgh Medical Center, Williamsport, PA, USA; 9Pain Medicine, MVM Health, East Stroudsburg, PA, USA; 10Anesthesiology and Pain Medicine, Mayo Clinic, Phoenix, AZ, USA; 11Interventional Pain Management, Napa Valley Orthopaedic Medical Group, Napa, CA, USA; 12Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 13Department of Rehabilitation & Regenerative Medicine, New York Presbyterian – Columbia & Cornell, New York, NY, USA; 14Director of Clinical Research, Boomerang Healthcare, Walnut Creek, CA, USA; 15Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA; 16Neuroradiology & Pain Solutions of Oklahoma, Edmond, OK, USA; 17The Spine Center of SE Georgia, Brunswick, GA, USA; 18Anesthesiology, University of Wisconsin, Madison, WI, USACorrespondence: Dawood Sayed, Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA, Tel +1 785-550-5800, Email [email protected]

A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis

Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In some HS patients, mutations in the ankyrin promoter have been hypothesized to lead to decreased ankyrin mRNA synthesis. The ankyrin erythroid promoter is a member of the most common class of mammalian promoters which lack conserved TATA, initiator or other promoter cis elements and have high G+C content, functional Sp1 binding sites and multiple transcription initiation sites. We identified a novel ankyrin gene promoter mutation, a TG deletion adjacent to a transcription initiation site, in a patient with ankyrin-linked HS and analyzed its effects on ankyrin expression. In vitro, the mutant promoter directed decreased levels of gene expression, altered transcription initiation site utilization and exhibited defective binding of TATA-binding protein (TBP) and TFIID complex formation. In a transgenic mouse model, the mutant ankyrin promoter led to abnormalities in gene expression, including decreased expression of a reporter gene and altered transcription initiation site utilization. These data indicate that the mutation alters ankyrin gene transcription and contributes to the HS phenotype by decreasing ankyrin gene synthesis via disruption of TFIID complex interactions with the ankyrin core promoter. These studies support the model that in promoters that lack conserved cis elements, the TFIID complex directs preinitiation complex formation at specific sites in core promoter DNA and provide the first evidence that disruption of TBP binding and TFIID complex formation in this type of promoter leads to alterations in start site utilization, decreased gene expression and a disease phenotype in viv

Intrathecal Drug Delivery Systems Survey: Trends in Utilization in Pain Practice [Corrigendum]

Abd-Sayed A, Fiala K, Weisbein J, et al. J Pain Res. 2022;15:1305–1314. The authors have advised there is an error in the author list on page 1305. The author name “Alaa Abd-Sayed” should read “Alaa Abd-Elsayed”. The authors apologize for this error

Medical Cannabis: A Review from the American Society of Pain and Neuroscience

Natalie Strand,1 Ryan S D’Souza,2 Jay Karri,3 Hemant Kalia,4 Jackie Weisbein,5 Brian J Kassa,6 Nasir Hussain,7 Ahish Chitneni,8 Ryan R Budwany,9 Jonathan Hagedorn,2 Jason E Pope,10 Timothy R Deer,11 Dawood Sayed,12 Alaa Abd-Elsayed13 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA; 2Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 3Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA; 4Department of Physical Medicine and Rehabilitation, Rochester Regional Health, Rochester, NY, USA; 5Napa Valley Orthopaedic, Napa, CA, USA; 6Resident in the Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine at the Rehabilitation Institute of Michigan, Detroit, MI, USA; 7Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 8Department of Physical Medicine & Rehabilitation, New York-Presbyterian, New York, NY, USA; 9Resident in the Department of Anesthesiology, West Virginia University, Charleston, WV, USA; 10Interventional Pain Management, Evolve Restorative Center, Santa Rosa, CA, USA; 11Department of Anesthesiology, West Virginia University School of Medicine, Morgantown, WV, USA; 12Department of Anesthesiology, The University of Kansas Medical Center, Kansas City, KS, USA; 13Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USACorrespondence: Natalie Strand, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA, Email [email protected]: Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions. Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported. However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.Keywords: analgesia, chronic pain, marijuana treatment, neuralgia, postoperative pai

Best Practices for Dorsal Root Ganglion Stimulation for Chronic Pain: Guidelines from the American Society of Pain and Neuroscience

Kenneth B Chapman,1– 3 Dawood Sayed,4 Tim Lamer,5 Corey Hunter,6 Jacqueline Weisbein,7 Kiran V Patel,1– 3 David Dickerson,8,9 Jonathan M Hagedorn,10 David W Lee,11 Kasra Amirdelfan,12 Timothy Deer,13 Krishnan Chakravarthy14,15 1The Spine & Pain Institute of New York, New York, NY, USA; 2Department of Anesthesiology, Zucker School of Medicine at Hofstra Northwell, Manhasset, NY, USA; 3Department of Anesthesiology, NYU Langone Medical Center, New York, NY, USA; 4Department of Anesthesiology, The University of Kansas Medical Center (KUMC), Kansas City, KS, USA; 5Department of Anesthesiology and Perioperative Medicine, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 6Ainsworth Institute of Pain Management, New York, NY, USA; 7Napa Valley Orthopedic Medical Group, Napa, CA, USA; 8Department of Anesthesiology, Critical Care and Pain Medicine, NorthShore University Health System, Evanston, IL, USA; 9Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, USA; 10iSpine Pain Physicians, Maple Grove, MN, USA; 11Fullerton Orthopedic Surgery Medical Group, Fullerton, CA, USA; 12IPM Medical Group, Inc., Walnut Creek, CA, USA; 13The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 14Department of Anesthesiology and Pain Medicine, University of California San Diego Health Sciences, San Diego, CA, USA; 15VA San Diego Healthcare System, San Diego, CA, USACorrespondence: Kenneth B Chapman, NYU Langone Medical Center, Zucker School of Medicine at Hofstra/Northwell, Pain Medicine at Staten Island University Hospital, 1360 Hylan Boulevard, Staten Island, NY, 10305, USA, Email [email protected]: With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion stimulation (DRG-S) has significantly improved the treatment of complex regional pain syndrome (CRPS), and it has broad applicability across a wide range of other conditions. Through funding and organizational leadership by the American Society for Pain and Neuroscience (ASPN), this best practices consensus document has been developed for the selection, implantation, and use of DRG stimulation for the treatment of chronic pain syndromes. This document is composed of a comprehensive narrative literature review that has been performed regarding the role of the DRG in chronic pain and the clinical evidence for DRG-S as a treatment for multiple pain etiologies. Best practice recommendations encompass safety management, implantation techniques, and mitigation of the potential complications reported in the literature. Looking to the future of neuromodulation, DRG-S holds promise as a robust intervention for otherwise intractable pain.Keywords: dorsal root ganglion, neurostimulation, chronic pain, best practice, guideline

Variegated Expression from the Murine Band 3 (AE1) Promoter in Transgenic Mice Is Associated with mRNA Transcript Initiation at Upstream Start Sites and Can Be Suppressed by the Addition of the Chicken β-Globin 5′ HS4 Insulator Element

The anion exchanger protein 1 (AE1; band 3) is an abundant erythrocyte transmembrane protein that regulates chloride-bicarbonate exchange and provides an attachment site for the erythrocyte membrane skeleton on the cytoplasmic domain. We analyzed the function of the erythroid AE1 gene promoter by using run-on transcription, RNase protection, transient transfection, and transgenic mouse assays. AE1 mRNA was transcribed at a higher level and maintained at a higher steady-state level than either ankyrin or β-spectrin in mouse fetal liver cells. When linked to a human γ-globin gene, two different AE1 promoters directed erythroid-specific expression of γ-globin mRNA in 18 of 18 lines of transgenic mice. However, variegated expression of γ-globin was observed in 14 of 18 lines. While there was a significant correlation between transgene copy number and the amount of γ-globin mRNA in all 18 lines, the transgene mRNAs initiated upstream of the start site of the endogenous AE1 mRNA. Addition of the insulator element from 5′HS4 of the chicken β-globin cluster to the AE1/γ-globin transgene allowed position-independent, copy-number-dependent expression at levels similar to the AE1 transcription rate in six of six lines of transgenic mice. The mRNA from the insulated AE1/γ-globin transgene mapped to the start site of the endogenous AE1 mRNA, and γ-globin protein was expressed in 100% of erythrocytes in all lines. We conclude that the chicken β-globin 5′HS4 element is necessary for full function of the AE1 promoter and that position effect variegation is associated with RNA transcription from the upstream start sites