title: Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse.
abstract: Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml(-1)·min(-1)), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California;
authors: T
authors: T
authors: Akiyama
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California;
authors: M
authors: M
authors: Nagamine
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California;
authors: A
authors: A
authors: Davoodi
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California;
authors: M
authors: M
authors: Iodi Carstens
authors: Departments of Dermatology and Surgery, University of California, San Francisco, California; and.
authors: F
authors: F
authors: Cevikbas
authors: Department of Dermatology and Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland.
authors: M
authors: M
authors: Steinhoff
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; eecarstens@ucdavis.edu.
authors: E
authors: E
authors: Carstens
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001839:Bombesin / Q000633:toxicity*; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D019332:Endothelin-1 / Q000008:administration & dosage*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007271:Injections, Intradermal; D008159:Lumbar Vertebrae; D008297:Male; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D011537:Pruritus / Q000503:physiopathology; D014110:Touch / Q000187:drug effects / Q000502:physiology
chemical_list: D002491:Central Nervous System Agents; D019332:Endothelin-1; D006993:Hypnotics and Sedatives; D010424:Pentobarbital; D001839:Bombesin
keywords: bombesin; endothelin-1; itch; pain; superficial dorsal horn