NGF up-regulates TRPA1: implications for orofacial pain.
The transient receptor potential ankyrin repeat 1 (TRPA1) channel is believed to be involved in many forms of acute and chronic hyperalgesia. Nerve Growth Factor (NGF) regulates chronic inflammatory hyperalgesia by controlling gene expression in sensory neurons, including genes involved in inflammatory hyperalgesia in the dental pulp. We hypothesized that NGF increases functional activities of the TRPA1 channel in trigeminal ganglion neurons. Here, we show that NGF induced a concentration- and time-dependent up-regulation of TRPA1 mRNA in trigeminal ganglia neurons, as detected by real-time RT-PCR and in situ hybridization. In addition, NGF evoked a time-dependent increase of mustard oil (MO)-evoked TRPA1 activation in trigeminal ganglia neurons. Collectively, these findings demonstrate that NGF participates in the functional up-regulation of TRPA1 in trigeminal ganglia neurons. These enhanced activities of TRPA1 could play an important role in the development of hyperalgesia following nerve injury and inflammation in the orofacial region.
Diogenes
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Departments of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Akopian
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Hargreaves
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KM
D000818:Animals; D017089:Ankyrin Repeat / Q000187:drug effects*; D017487:Ankyrins; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005157:Facial Pain / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D013997:Time Factors; D050051:Transient Receptor Potential Channels / Q000187:drug effects*; D012668:Trigeminal Ganglion / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
D017487:Ankyrins; D015220:Calcium Channels; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C480976:Trpa1 protein, rat; D020932:Nerve Growth Factor