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

Autor: Sapio MR; Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States., Iadarola MJ; Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States., LaPaglia DM; Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States., Lehky T; Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States., Thurm AE; Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health (NIH), Bethesda, MD, United States., Danley KM; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States., Fuhr SR; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States., Lee MD; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States., Huey AE; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States., Sharp SJ; Departent of Neurology, Uniformed Services University, Bethesda, MD, United States., Tsao JW; Departent of Neurology, Uniformed Services University, Bethesda, MD, United States.; Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, United States.; Department of Neurology, Memphis Veterans Affairs Medical Center, Memphis, TN, United States.; Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN, United States., Yanovski JA; Section on Growth and Obesity, NICHD, NIH, Bethesda, MD, United States., Mannes AJ; Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States., Han JC; Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health (NIH), Bethesda, MD, United States.; Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States.; Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN, United States.; Section on Growth and Obesity, NICHD, NIH, Bethesda, MD, United States.; Departments of Pediatrics and.; Physiology, University of Tennessee Health Science Center, Memphis, TN, United States.
Jazyk: angličtina
Zdroj: Pain [Pain] 2019 May; Vol. 160 (5), pp. 1070-1081.
DOI: 10.1097/j.pain.0000000000001485
Abstrakt: 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 (BDNF) 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 BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. 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 BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.
Databáze: MEDLINE