The underlying mechanisms of itch are poorly understood. We have investigated a model involving the chemoattractant leukotriene B₄ (LTB₄) that is up-regulated in common skin diseases. Intradermal injection of LTB4 (0.1 nmol/site) into female CD1 mice induced significant scratching movements (used as an itch index) compared with vehicle-injected (0.1% bovine serum albumin-saline) mice. Intraperitoneal transient receptor potential (TRP) channel antagonist treatment significantly inhibited itch as follows: TRP vanilloid 1 (TRPV1) antagonist SB366791 (0.5 mg/kg, by 97%) and the TRP ankyrin 1 (TRPA1) antagonists TCS 5861528 (10 mg/kg; 82%) and HC-030031 (100 mg/kg; 76%). Leukotriene B₄ receptor 2 antagonism by LY255283 (5 mg/kg i.p.; 62%) reduced itch. Neither TRPV1-knockout (TRPV1-KO) nor TRPA1-knockout (TRPA1-KO mice exhibited LTB₄-induced itch compared with their wild-type counterparts. The reactive oxygen species scavengers N-acetylcysteine (NAC; 204 mg/kg i.p.; 86%) or superoxide dismutase (SOD; 10 mg/kg i.p.; 83%) also inhibited itch. LTB4-induced superoxide release was attenuated by TCS 5861528 (56%) and HC-030031 (66%), NAC (58%), SOD (50%), and LY255283 (59%) but not by the leukotriene B4 receptor 1 antagonist U-75302 (9 nmol/site) or SB366791. Itch, superoxide, and myeloperoxidase generation were inhibited by the leukocyte migration inhibitor fucoidan (10 mg/kg i.v.) by 80, 61, and 34%, respectively. Myeloperoxidase activity was also reduced by SB366791 (35%) and SOD (28%). TRPV1-KO mice showed impaired myeloperoxidase release, whereas TRPA1-KO mice exhibited diminished production of superoxide. This result provides novel evidence that TRPA1 and TRPV1 contribute to itch via distinct mechanisms.

BackgroundTrauma team activation criteria have a variable performance in the paediatric population. We aimed to identify predictors for high-level resource utilisation during trauma resuscitation in the ED.MethodsA retrospective study was conducted in the ED of a tertiary paediatric hospital. Patient data were collected from trauma surveillance registry and analysis was performed to identify significant predictors. We then assessed the sensitivity and specificity of proposed models with respect to observed patient outcomes.ResultsAmong 11 282 cases, the mean age was 6.1±4.9 (SD) years old. Fall was the most common mechanism of injury in 7364 (65.3%) patients. Eighty-eight (0.8%) patients required at least one high-level resource. Significant predictors for high-resource utilisation were overall GCS of <14 (relative risk (RR) 38.841, 95% CI 21.328 to 70.739, p<0.001), high-risk mechanisms of fall from height and motor vehicle collision (RR 7.863, 95% CI 4.687 to 13.192, p<0.001), as well as age-specific tachycardia (RR 1.796, 95% CI 1.145 to 2.817, p=0.0108). A model consisting of GCS and high-risk mechanism would under-triage 21 (0.2%) patients and over-triage 681 (6.0%) patients. When age-specific tachycardia was added, 8 (0.1%) less patients would be under-triaged but an additional 3251 (28.9%) patients would be over-triaged.ConclusionAs utilisation of high-level resources in paediatric trauma was rare, it was difficult to find an appropriate balance between under-triage and over-triage. Between the two, minimising the proportion of under-triage is more important as patient safety is paramount in paediatric trauma care.