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Effects of the neurotrophic factor artemin on sensory afferent developmentand sensitivity

Shuying WANG, Christopher M. Elitt, Sacha A. Malin, Kathryn M. Albers

Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA

摘要

Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptorGFRá3 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 arteminin keratinocytes of the skin and tongue. Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons andincreases in the level of mRNA encoding TRPV1 and TRPA1. Calcium imaging showed that isolated sensory neurons from ARTN-OEmice were hypersensitive to the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil. Behavioral testing of ARTN-OE micealso 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. Inaddition, injection of artemin into hindpaw skin produced transient thermal hyperalgesia. These findings indicate that artemin canmodulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNAexpression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underliepain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.

关键词： pain; nociceptor; GFRα3; skin; tongue; sensitization

Effects of the neurotrophic factor artemin on sensory afferent developmentand sensitivity

Shuying WANG, Christopher M. Elitt, Sacha A. Malin, Kathryn M. Albers

Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA

Abstract

Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptorGFRá3 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 arteminin keratinocytes of the skin and tongue. Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons andincreases in the level of mRNA encoding TRPV1 and TRPA1. Calcium imaging showed that isolated sensory neurons from ARTN-OEmice were hypersensitive to the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil. Behavioral testing of ARTN-OE micealso 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. Inaddition, injection of artemin into hindpaw skin produced transient thermal hyperalgesia. These findings indicate that artemin canmodulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNAexpression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underliepain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.

Key words: pain; nociceptor; GFRα3; skin; tongue; sensitization

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引用本文：

Shuying WANG, Christopher M. Elitt, Sacha A. Malin, Kathryn M. Albers. Effects of the neurotrophic factor artemin on sensory afferent developmentand sensitivity[J]. 生理学报 2008; 60 (5): 565-570.

Shuying WANG, Christopher M. Elitt, Sacha A. Malin, Kathryn M. Albers. Effects of the neurotrophic factor artemin on sensory afferent developmentand sensitivity. Acta Physiol Sin 2008; 60 (5): 565-570 (in Chinese with English abstract).