title: Sickle cell disease in mice is associated with sensitization of sensory nerve fibers.
abstract: The pain phenotype in sickle cell disease (SCD) patients is highly variable. A small percentage of SCD patients experience many vaso-occlusive crises/year, 5% of patients account for over 30% of pain episodes, while 39% report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. Researchers have shown that one strain of humanized SCD mice, the BERK strain, has abnormal pain phenotype. However, the nociception phenotype of another humanized SCD mouse strain, the Townes strain, has not been described. In a large cross-sectional study of BERK and Townes SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5 Hz to stimulate preferentially Aβ, Aδ, and C sensory nerve fibers, respectively. We found that BERK and Townes mice, compared to respective controls, had decreases in 2000, 250, and 5 Hz current vocalization thresholds in patterns that suggest sensitization of a broad spectrum of sensory nerve fibers. In addition, the pattern of sensitization of sensory fibers varied according to strain, sex, age, and mouse genotype. In a similarly variable pattern, Townes and BERKs also had significantly altered sensitivity to noxious thermal stimuli in agreement with what has been shown by others. In summary, the analysis of somatosensory function using sine-wave electrical stimulation in humanized sickle cell mice suggests that in SCD, both myelinated and unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization is distinct from that observed in pain models of neuropathic and inflammatory pain. These findings raise the possibility that sensitization of a broad spectrum of sensory fibers might contribute to the altered and variable nociception phenotype in SCD.
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA.
authors: Nicholas
authors: N
authors: Kenyon
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA.
authors: Li
authors: L
authors: Wang
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA.
authors: Nicholas
authors: N
authors: Spornick
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA.
authors: Alfia
authors: A
authors: Khaibullina
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA.
authors: Luis Ef
authors: LE
authors: Almeida
authors: Division of Biostatistics and Study Methodology, Center for Translational Science, Children's National Medical Center, Washington, DC 20010, USA.
authors: Yao
authors: Y
authors: Cheng
authors: Division of Biostatistics and Study Methodology, Center for Translational Science, Children's National Medical Center, Washington, DC 20010, USA.
authors: Jichuan
authors: J
authors: Wang
authors: Department of Perioperative Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA.
authors: Virginia
authors: V
authors: Guptill
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA.
authors: Julia C
authors: JC
authors: Finkel
authors: Children's Research Institute, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Division of Pain Medicine, Children's National Medical Center, School of Medicine and Health Sciences, George Washington University, Washington, DC 20010, USA zquezado@childrensnational.org.
authors: Zenaide M N
authors: ZM
authors: Quezado
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D000818:Animals; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000502:physiology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D012678:Sensation Disorders / Q000209:etiology* / Q000503:physiopathology*
keywords: Sickle cell; fetal hemoglobin; nociception; pain; sine wave; somatosensory