Effects of the neurotrophic factor artemin on sensory afferent development and sensitivity  

作　　者：Shuying WANG Christopher M. Elitt Sacha A. Malinx Sacha A. Malin Kathryn M. Albers 

机构地区：[1]Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA

出　　处：《生理学报》2008年第5期565-570,共6页Acta Physiologica Sinica

摘　　要：Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family.Its receptor GFRα3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia(DRG and TG).These neurons co-express the heat,capsaicin and proton-sensitive channel TRPV1 and the cold and chemical-sensitive channel TRPA1.To further investigate the effects of artemin on sensory neurons,we isolated transgenic mice(ARTN-OE mice) that overexpress artemin in keratinocytes of the skin and tongue.Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons and increases in the level of mRNA encoding TRPV1 and TRPA1.Calcium imaging showed that isolated sensory neurons from ARTN-OE mice were hypersensitive to the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil.Behavioral testing of ARTN-OE mice also showed an increased sensitivity to heat,cold,capsaicin and mustard oil stimuli applied either to the skin or in the drinking water.Sensory neurons from wildtype mice also exhibited potentiated capsaicin responses following artemin addition to the media.In addition,injection of artemin into hindpaw skin produced transient thermal hyperalgesia.These findings indicate that artemin can modulate sensory function and that this regulation may occur through changes in channel gene expression.Because artemin mRNA expression is up-regulated in inflamed tissue and following nerve injury,it may have a significant role in cellular changes that underlie pain associated with pathological conditions.Manipulation of artemin expression may therefore offer a new pain treatment strategy.Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptor GFRα3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia （DRG and TG）. These neurons co-express the heat, capsaicin and proton-sensitive channel TRPV1 and the cold and chemical-sensitive channel TRPA1. To further investigate the effects of artemin on sensory neurons, we isolated transgenic mice （ARTN-OE mice） that overexpress artemin in keratinocytes of the skin and tongue. Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons and increases in the level of mRNA encoding TRPV 1 and TRPA 1. Calcium imaging showed that isolated sensory neurons from ARTN-OE mice were hypersensitive to the TRPV 1 agonist capsaicin and the TRPA 1 agonist mustard oil. Behavioral testing of ARTN-OE mice also showed an increased sensitivity to heat, cold, capsaicin and mustard oil stimuli applied either to the skin or in the drinking water. Sensory neurons from wildtype mice also exhibited potentiated capsaicin responses following artemin addition to the media. In addition, injection of artemin into hindpaw skin produced transient thermal hyperalgesia. These findings indicate that artemin can modulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNA expression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underlie pain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.

关 键 词：神经系统 敏感性 细胞 感觉传入系统 舌 

分 类 号：Q42[生物学—神经生物学] Q26[生物学—生理学]