title: Excitation of mouse superficial dorsal horn neurons by histamine and/or PAR-2 agonist: potential role in itch.
abstract: Recent studies have suggested the existence of separate transduction mechanisms and sensory pathways for histamine and nonhistaminergic types of itch. We studied whether histamine and an agonist of the protease-activated receptor (PAR)-2, associated with nonhistaminergic itch, excite murine dorsal horn neurons. Single units were recorded in superficial lumbar dorsal horn of adult ICR mice anesthetized with pentobarbital. Unit activity was searched using a small intradermal hindpaw injection of histamine or the PAR-2 agonist SLIGRL-NH2. Isolated units were subsequently challenged with intradermal histamine followed by SLIGRL-NH2 (each 50 microg/1 microl) or reverse order, followed by mechanical, thermal, and algogenic stimuli. Forty-three units were classified as wide dynamic range (62%), nociceptive specific (22%), or mechano insensitive (16%). Twenty units gave prolonged (mean, 10 min) discharges to intradermal injection of histamine; 76% responded to subsequent SLIGRL-NH2, often more briefly. Units additionally responded to noxious heat (63%), cooling (43%), topical mustard oil (53%), and intradermal capsaicin (67%). Twenty-two other units gave prolonged (mean, 5 min) responses to initial intradermal injection of SLIGRL-NH2; 85% responded to subsequent intradermal histamine. They also responded to noxious heat (75%), mustard oil (93%), capsaicin (63%), and one to cooling. Most superficial dorsal horn neurons were excited by both histamine and the PAR-2 agonist, suggesting overlapping pathways for histamine- and non-histamine-mediated itch. Because the large majority of pruritogen-responsive neurons also responded to noxious stimuli, itch may be signaled at least partly by a population code.
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California 95616, USA.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000200:Action Potentials; D000818:Animals; D002211:Capsaicin; D003080:Cold Temperature; D006632:Histamine / Q000378:metabolism*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009149:Mustard Plant; D009474:Neurons / Q000502:physiology*; D009842:Oligopeptides / Q000378:metabolism*; D010812:Physical Stimulation; D010938:Plant Oils; D020671:Posterior Horn Cells / Q000503:physiopathology*; D011537:Pruritus / Q000139:chemically induced / Q000503:physiopathology*; D044464:Receptor, PAR-2 / Q000819:agonists*
chemical_list: D009842:Oligopeptides; D010938:Plant Oils; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D006632:Histamine; D002211:Capsaicin; C027793:mustard oil