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Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 . Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.A llergic contact dermatitis (ACD) is a common allergic skin condition caused by environmental or occupational allergens (1). In the United States, the most common cause of ACD is contact with poison ivy, which affects >10 million Americans per year (2, 3). Poison ivy ACD is also a serious occupational hazard, particularly among firefighters, forestry workers, and farmers, accounting for 10% of total U.S. Forest Services losttime injuries, and it often torments outdoor enthusiasts as well (3, 4). The major allergen in poison ivy is urushiol, contained in the oleoresinous sap of the plant and of related plants (e.g., poison oak and poison sumac) (5). An estimated 50-75% of Americans are sensitized to urushiol (6). Elevated atmospheric carbon dioxide and warming temperatures have increased the biomass of poison ivy and related plants, widened their geographic distribution, and increased plant urushiol content (7). These factors will likely increase allergenicity and result in even larger case numbers of poison ivy ACD in the future (8).The clinical manifestations of poison ivy-induced ACD are intense and persistent itch (pruritus), burning sensation, skin rashes, and swelling, followed by the appearance of vesicles in severe cases (2, 3, 9). Skin inflammation and pruritus ...

Insulin-like growth factor (IGF-1) markedly increases myelination and glial numbers in white matter after ischemia in near-term fetal sheep; however, it is unclear whether this is due to reduced cell loss or increased secondary proliferation. Brain injury was induced in near-term fetal sheep by 30 minutes of bilateral carotid artery occlusion. Ninety minutes after the occlusion, fetuses were given, intracerebroventricularly, either a single dose of IGF-1 (either 3 or 30 micro g), or 3 micro g followed by 3 micro g over 24 hours (3 + 3 micro g). White matter was assessed 4 days after reperfusion. Three micrograms, but not 30 micro g of IGF-1 prevented loss of oligodendrocytes and myelin basic protein density (P < 0.001) compared to the vehicle-treated ischemia controls. No additional effect was observed in the 3 + 3 micro g group. IGF-1 treatment was associated with reduced caspase-3 activation and increased glial proliferation in a similar dose-dependent manner. Caspase-3 was only expressed in oligodendrocytes that showed apoptotic morphology. Proliferating cell nuclear antigen co-localized with both oligodendrocytes and astrocytes and microglia. Thus, increased oligodendrocyte numbers after IGF-1 treatment is partly due to suppression of apoptosis, and partly to increased proliferation. In contrast, the increase in reactive glia was related only to proliferation. Speculatively, reactive glia may partly mediate IGF-1 white matter protection.

Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca2+ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA’s effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain.

BackgroundA deviant motor behaviour at age 3 to 5 months is predictive of cerebral palsy (CP). Particular features of the early motor repertoire even proved predictive of the degree of functional limitations as classified on the Gross Motor Function Classification System (GMFCS) in children with CP, born preterm.AimsWe aimed to determine whether an association between the early motor repertoire and the GMFCS also holds true for children born at term.Study designLongitudinal study.Subjects79 infants (60 boys and 19 girls; 47 infants born at term; video recorded for the assessment of movements and posture at age 9 to 20 weeks postterm age) who developed CP.Outcome measuresThe GMFCS was applied at age 2 to 5 years.ResultsMotor optimality at age 3 to 5 months showed a significant correlation with functional mobility and activity limitation as classified on the GMFCS at age 2 to 5 years in both children born at term (Spearman rho = − 0.66, p < 0.001) and born preterm (rho = − 0.37, p < 0.05). Infants born preterm were more likely to show normal movement patterns than infants born at term. A normal posture and an abnormal, jerky (yet not monotonous) movement character resulted in better levels of function and mobility. With the exception of one, none of the infants showed fidgety movements. A cramped-synchronised movement character, repetitive opening and closing of the mouth, and abnormal finger postures characterised children who would show a poor self-mobility later.ConclusionsAssessing the quality of motor performance at 9 to 20 weeks postterm age (irrespective of the gestational age) improves our ability to predict later functional limitations in children with CP.