Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity

  • Matthew R. Sapio
    Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States
  • Michael J. Iadarola
    Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States
  • Danielle M. LaPaglia
    Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States
  • Tanya Lehky
    Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States
  • Audrey E. Thurm
    Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health (NIH), Bethesda, MD, United States
  • Kristen M. Danley
    Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States
  • Shannon R. Fuhr
    Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States
  • Mark D. Lee
    Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States
  • Amanda E. Huey
    Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States
  • Stephen J. Sharp
    Departent of Neurology, Uniformed Services University, Bethesda, MD, United States
  • Jack W. Tsao
    Departent of Neurology, Uniformed Services University, Bethesda, MD, United States
  • Jack A. Yanovski
    Section on Growth and Obesity, NICHD, NIH, Bethesda, MD, United States
  • Andrew J. Mannes
    Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States
  • Joan C. Han
    Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health (NIH), Bethesda, MD, United States

抄録

<jats:title>Abstract</jats:title> <jats:p>Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (<jats:italic toggle="yes">BDNF</jats:italic>) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the <jats:italic toggle="yes">BDNF</jats:italic> gene. Corresponding behavioral assessments were made in heterozygous <jats:italic toggle="yes">Bdnf</jats:italic> knockout rats to examine the specific role of <jats:italic toggle="yes">Bdnf</jats:italic>. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the <jats:italic toggle="yes">BDNF</jats:italic> gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.</jats:p>

収録刊行物

  • Pain

    Pain 160 (5), 1070-1081, 2019-02-27

    Ovid Technologies (Wolters Kluwer Health)

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