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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-5-26
pubmed:abstractText
TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17 degrees C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised with a subset of hDRG neurons positive for TRPV1, the heat and capsaicin receptor. The number of small/medium TRPA1 positive neurons (< or =50 microm) was increased after hDRG avulsion injury [percentage of cells, median (range): controls 16.5 (7-23); injured 46 (34-55); P<0.005], but the number of large TRPA1 neurons was unchanged [control 19.5 (13-31); injured 21 (11-35)]. Similar TRPA1 changes were observed in cultured hDRG neurons, after exposure to a combination of key neurotrophic factors NGF, GDNF and NT-3 (NTFs) in vitro. We used calcium imaging to examine responses of HEK cells transfected with hTRPA1 cDNA, and of human and rat DRG neurons cultured with or without added NTFs, to cinnamaldehyde (CA) and isoeugenol (IE). Exposure to NTFs in vitro sensitized cultured human sensory neuronal responses to CA; repeated CA exposure produced desensitisation. In rDRG neurons, low (225 microM) CA preincubation enhanced capsaicin responses, while high (450 microM and 2mM) CA caused inhibition which was partially reversed in the presence of 8 bromo cAMP, indicating receptor dephosphorylation. While TRPA1 localisation is more widespread than TRPV1, it represents a promising novel drug target for the treatment of chronic pain and hypersensitivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
438
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-7
pubmed:meshHeading
pubmed-meshheading:18456404-Adolescent, pubmed-meshheading:18456404-Adult, pubmed-meshheading:18456404-Aged, pubmed-meshheading:18456404-Aged, 80 and over, pubmed-meshheading:18456404-Animals, pubmed-meshheading:18456404-Calcium Channels, pubmed-meshheading:18456404-Calcium Signaling, pubmed-meshheading:18456404-Cells, Cultured, pubmed-meshheading:18456404-Child, Preschool, pubmed-meshheading:18456404-Female, pubmed-meshheading:18456404-Ganglia, Spinal, pubmed-meshheading:18456404-Humans, pubmed-meshheading:18456404-Immunohistochemistry, pubmed-meshheading:18456404-Irritants, pubmed-meshheading:18456404-Male, pubmed-meshheading:18456404-Middle Aged, pubmed-meshheading:18456404-Nerve Growth Factors, pubmed-meshheading:18456404-Nerve Tissue Proteins, pubmed-meshheading:18456404-Neurons, Afferent, pubmed-meshheading:18456404-Nociceptors, pubmed-meshheading:18456404-Pain, pubmed-meshheading:18456404-Peripheral Nervous System, pubmed-meshheading:18456404-Rats, pubmed-meshheading:18456404-Rats, Wistar, pubmed-meshheading:18456404-Rhizotomy, pubmed-meshheading:18456404-TRPV Cation Channels, pubmed-meshheading:18456404-Transient Receptor Potential Channels
pubmed:year
2008
pubmed:articleTitle
TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons.
pubmed:affiliation
Peripheral Neuropathy Unit, Imperial College London, Area A, Ground Floor, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. uma.anand@cancer.org.uk
pubmed:publicationType
Journal Article