title: Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model.
abstract: Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.
authors: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, CA 95616, USA.
authors: Tasuku
authors: T
authors: Akiyama
authors: Mirela Iodi
authors: MI
authors: Carstens
authors: E
authors: E
authors: Carstens
mesh_terms: D000096:Acetone / Q000009:adverse effects; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000982:Antipruritics / Q000627:therapeutic use; D002211:Capsaicin / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D007839:Functional Laterality; D006632:Histamine / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology*; D010812:Physical Stimulation / Q000009:adverse effects; D020671:Posterior Horn Cells / Q000187:drug effects*; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D044462:Receptors, Proteinase-Activated / Q000819:agonists*; D012701:Serotonin / Q000494:pharmacology; D012997:Solvents / Q000009:adverse effects; D013116:Spinal Cord / Q000473:pathology; D014867:Water / Q000009:adverse effects
chemical_list: D000982:Antipruritics; D017879:Isothiocyanates; D009842:Oligopeptides; D044462:Receptors, Proteinase-Activated; D012997:Solvents; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D014867:Water; D000096:Acetone; D012701:Serotonin; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D006632:Histamine; D002211:Capsaicin