Brain-derived neurotrophic factor (BDNF) plays a critical role in pain sensitivity and may provide novel approaches to pain management. In collaboration with colleagues at the NIH, Joan Han, MD, and Jack Tsao, MD, PhD, examined the role of BDNF in pain sensitivity in individuals with Wilms tumor, aniridia, genitourinary anomaly, range of intellectual disabilities (WAGR) with or without heterozygous deletion of the Bdnf gene as well as heterozygous Bdnf knockout rats. Given BDNF’s known role in pain, the authors hypothesized that Bdnf haploinsufficiency would alter pain sensitivity in rats and human subjects with WAGR.
Among participants with WAGR, those with BDNF haploinsufficiency were more likely to exhibit pain insensitivity than those without haploinsufficiency, as indicated by parental reports and quantitative sensory testing. Among the subset of genes that differentiates subjects with WAGR with BDNF haploinsufficiency from those without, BDNF was more highly enriched in pain circuit regions than in other regions of the human body. Consistent with findings in human subjects, heterozygous Bdnf knockout rats exhibited reduced thermal nociception. Both WAGR subjects with BDNF haploinsufficiency and heterozygous Bdnf knockout rats responded to markedly strong stimulation, indicating a blunted response to aversive stimuli. Overall, these findings suggest that the complex trait of pain sensitivity is modulated by a large gene network that may encompass BDNF, which has broad implications for novel analgesic approaches.
M.R. Sapio, M.J. Iadarola, D.M. LaPaglia, T. Lehky, A.E. Thurm, K.M. Danley, S.R. Fuhr, M.D. Lee, A.E. Huey, S.J. Sharp, J.W. Tsao, J.A. Yanovski, A.J. Mannes, and J.C. Han. Haploinsufficiency of the brain-derived neurotrophic factor (BDNF) gene is associated with reduced pain sensitivity, Pain, Volume 160(5), May 2019, Pages 1070-1081, https://doi.org/10.1097/j.pain.0000000000001485
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