title: Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse.
abstract: Itch is often triggered by warming the skin in patients with itchy dermatitis, but the underlying mechanism is largely unknown. We presently investigated if warming the skin enhances histamine- or serotonin (5-HT)-evoked itch behavior or responses of sensory dorsal root ganglion (DRG) cells, and if responses of superficial dorsal horn neurons to innocuous warming are enhanced by these pruritogens. In a temperature-controlled environmental chamber, mice exhibited greater scratching following intradermal injection of 5-HT, but not histamine, SLIGRL, or BAM8-22, when the skin surface temperature was above 36°C. Calcium imaging of DRG cells in a temperature-controlled bath revealed that responses to 5-HT, but not histamine, were significantly greater at a bath temperature of 35°C vs. lower temperatures. Single-unit recordings revealed a subpopulation of superficial dorsal horn neurons responsive to intradermal injection of 5-HT. Of these, 58% responded to innocuous skin warming (37°C) prior to intradermal injection of 5-HT, while 100% responded to warming following intradermal injection of 5-HT. Warming-evoked responses were superimposed on the 5-HT-evoked elevation in firing and were significantly larger compared with responses pre-5-HT, as long as 30 min after the intradermal injection of 5-HT. Five-HT-insensitive units, and units that either did or did not respond to intradermal histamine, did not exhibit any increase in the incidence of warmth sensitivity or in the mean response to warming following intradermal injection of the pruritogen. The results suggest that 5-HT-evoked responses of pruriceptors are enhanced during skin warming, leading to increased firing of 5-HT-sensitive dorsal horn neurons that signal nonhistaminergic itch.
  
  
  
  Skin warming often exacerbates itch in patients with itchy dermatitis. We demonstrate that warming the skin enhanced serotonin-evoked, but not histamine-evoked, itch behavior and responses of sensory dorsal root ganglion cells. Moreover, serotonin, but not histamine, enhanced responses of superficial dorsal horn neurons to innocuous warming. The results suggest that skin warming selectively enhances the responses of serotonin-sensitive pruriceptors, leading to increased firing of serotonin-sensitive dorsal horn neurons that signal nonhistaminergic itch.
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and tasuku.akiyama@temple.edu.|Departments of Dermatology, Anatomy, and Cell Biology, Temple Itch Center, Temple University, Philadelphia, Pennsylvania.
authors: T
authors: T
authors: Akiyama
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and.
authors: M
authors: M
authors: Nagamine
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and.
authors: A
authors: A
authors: Davoodi
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and.
authors: M
authors: M
authors: Ivanov
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and.
authors: M Iodi
authors: MI
authors: Carstens
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; and.
authors: E
authors: E
authors: Carstens
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D006632:Histamine / Q000494:pharmacology; D007271:Injections, Intradermal; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects*; D011537:Pruritus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D018689:Sensory System Agents / Q000494:pharmacology; D012701:Serotonin / Q000633:toxicity*; D012881:Skin Temperature / Q000187:drug effects*; D013696:Temperature; D013997:Time Factors
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D018689:Sensory System Agents; C571042:bovine adrenal medulla 8-22; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; D012701:Serotonin; D006632:Histamine
keywords: 5-HT; histamine; itch; mice; pain; pruritus; spinal neurons; warming