title: Human sensory neurons: Membrane properties and sensitization by inflammatory mediators.
abstract: Biological differences in sensory processing between human and model organisms may present significant obstacles to translational approaches in treating chronic pain. To better understand the physiology of human sensory neurons, we performed whole-cell patch-clamp recordings from 141 human dorsal root ganglion (hDRG) neurons from 5 young adult donors without chronic pain. Nearly all small-diameter hDRG neurons (<50 μm) displayed an inflection on the descending slope of the action potential, a defining feature of rodent nociceptive neurons. A high proportion of hDRG neurons were responsive to the algogens allyl isothiocyanate (AITC) and ATP, as well as the pruritogens histamine and chloroquine. We show that a subset of hDRG neurons responded to the inflammatory compounds bradykinin and prostaglandin E2 with action potential discharge and show evidence of sensitization including lower rheobase. Compared to electrically evoked action potentials, chemically induced action potentials were triggered from less depolarized thresholds and showed distinct afterhyperpolarization kinetics. These data indicate that most small/medium hDRG neurons can be classified as nociceptors, that they respond directly to compounds that produce pain and itch, and that they can be activated and sensitized by inflammatory mediators. The use of hDRG neurons as preclinical vehicles for target validation is discussed.
authors: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA AnaBios Corporation, San Diego, CA 92109, USA.
authors: Steve
authors: S
authors: Davidson
authors: Bryan A
authors: BA
authors: Copits
authors: Jingming
authors: J
authors: Zhang
authors: Guy
authors: G
authors: Page
authors: Andrea
authors: A
authors: Ghetti
authors: Robert W
authors: RW
authors: Gereau
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000293:Adolescent; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002738:Chloroquine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D018408:Patch-Clamp Techniques; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D006632:Histamine; D002738:Chloroquine; D000255:Adenosine Triphosphate; D015232:Dinoprostone; D002211:Capsaicin; D001920:Bradykinin
keywords: Bradykinin; Dorsal root ganglia; Human; Itch; Nociception; Pain; Sensitization