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Differences in nociceptor physiology between humans and rodents is a major roadblock
in the successful translation of preclinical analgesic targets to clinical therapy.
Both acute and chronic inflammation by mediators like bradykinin (BK) has been implicated
in the pathogenesis of pain. However, to date, few studies have examined how BK modulates
the physiology of human sensory neurons. Furthermore, the expression pattern of BK
receptor subtypes in human dorsal root ganglion (hDRG) remains largely unknown. In
the present study, we perform patch clamp electrophysiology experiments to examine
the effects of acute and prolonged exposure to BK on the excitability of small-diameter
human sensory neurons, using primary hDRG tissue from organ donors as a translational
platform. Additionally, using in situ hybridization, we characterize the distribution
pattern of B1 and B2 bradykinin receptors among hDRG subpopulations based on size
and molecular markers. The results of the study may aid the evaluation of bradykinin
signaling as a target for clinical analgesic development. Grant support from American
Heart Association – 828671.
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© 2022 Published by Elsevier Inc.
