Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mitrovic, M; Shahbazian, A; Bock, E; Pabst, MA; Holzer, P.
Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels.
BRIT J PHARMACOL. 2010; 160(6): 1430-1442.
Doi: 10.1111/j.1476-5381.2010.00794.x
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- Führende Autor*innen der Med Uni Graz
- Holzer Peter
- Mitrovic Martina
- Co-Autor*innen der Med Uni Graz
- Bock Elisabeth
- Pabst Maria-Anna
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- Abstract:
- Background and purpose: Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker. Experimental approach: One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c-Fos in laminae I-IIo of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week. Key results: Relative to vehicle, AITC (2%) increased expression of c-Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c-Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg center dot kg-1) or the TRPA1 channel blocker HC-030031 (300 mg center dot kg-1) inhibited the spinal c-Fos response to AITC, in control and DSS-pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC-030031. Conclusions and implications: Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetanilides - pharmacology
- Animals -
- Capsaicin - pharmacology
- Colitis - physiopathology
- Colon - metabolism
- Dextran Sulfate - toxicity
- Disease Models, Animal -
- Female -
- Gene Expression Regulation - drug effects
- Isothiocyanates - toxicity
- Mice -
- Morphine - pharmacology
- Neurons, Afferent - metabolism
- Proto-Oncogene Proteins c-fos - genetics
- Purines - pharmacology
- Signal Transduction -
- Transient Receptor Potential Channels - antagonists and inhibitors
- Find related publications in this database (Keywords)
- allyl isothiocyanate
- capsaicin
- TRPA1
- TRPV1
- c-Fos expression
- colitis
- chemonociception
- chemical hyperresponsiveness
- abdominal pain
- morphine
- HC-030031