| First Author | Rossbach K | Year | 2011 |
| Journal | Neuroscience | Volume | 190 |
| Pages | 89-102 | PubMed ID | 21689731 |
| Mgi Jnum | J:175634 | Mgi Id | MGI:5286789 |
| Doi | 10.1016/j.neuroscience.2011.06.002 | Citation | Rossbach K, et al. (2011) Histamine H1, H3 and H4 receptors are involved in pruritus. Neuroscience 190:89-102 |
| abstractText | Histamine has long been recognised as a classical inducer of pruritus. However, the specific mechanism of histamine-induced itch has still not been fully understood. The H(1) and H(4) receptor appear to be key components in the induction of itch. The specific role of the H(3) receptor in histamine-induced itch remains unclear. The aim of our study was to investigate the role of the four known histamine receptors (H(1-4)R) in acute itch in mice. Intradermal injection of the selective H(3)R inverse agonist pitolisant induced strong itch in mice. Pitolisant (50 nmol/injection)-induced pruritus could be completely blocked by a combined treatment with the H(1)R antagonist cetirizine (15 mg/kg) and the H(4)R antagonist JNJ 7777120 (15 mg/kg), whereas the H(2)R antagonist ranitidine (15 mg/kg) failed to inhibit the scratch response. Next, expression and function of histamine receptors on sensory neurons isolated from dorsal root ganglia of mice were investigated. As the itch sensation results from the excitation of sensory nerves in the skin, we further focused on skin specific sensory neurons. Therefore, neurons were retrograde labelled from the skin by means of a fluorescent tracer. Expression of H(1)R, H(3)R and H(4)R on skin innervating sensory neurons was detected. By single-cell calcium imaging, it was demonstrated that histamine induces a calcium increase in a subset of (skin-specific) sensory neurons via activation of the H(1)R and H(4)R as well as inhibition of the H(3)R. It is assumed that the decreased threshold in response to H(3)R antagonism activates H(1)R and H(4)R on sensory neurons, which in turn results in the excitation of histamine-sensitive afferents and therefore elicits the sensation of itch. |
