Quantitative Mass Spectrometry Analysis Reveals that Deletion of the TRPV1 Receptor in Mice Alters Substance P and Neurokinin A Expression in the Central Nervous System
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Vanilloid receptors have a central role in the processing of nociceptive stimuli. TRPV1 null mice showed significant decrease in response to heat noxious stimuli. However, thermal sensitivity is still present suggesting that the TRPV1 is not an exclusive transducer of thermal stimuli. Additionally, tachykinin peptides play a central role in pain processing and expression levels may also contribute in modifying the pain threshold. The LC–MS/MS analysis revealed that SP and NKA were significantly down-regulated in TRPV1−/− in spinal cord and brain tissues. In spinal cord, SP concentrations were 23.4 % lower (p < 0.0049) and NKA concentrations were 22.0 % lower (p < 0.0022) in TRPV1 null mice. Additionally, brain SP concentrations were 26.9 % lower (p < 0.0260) and brain NKA concentrations were 31.9 % lower (p < 0.0063) in TRPV1 null mice. These results clearly demonstrate that TPRV1 null mice exhibit lower SP and NKA concentrations in the central nervous system. The deficit of thermal responses may also be related to the down-regulations of SP and NKA.
KeywordsTRPV1 Nociceptors Tachykinins Pain Mass spectrometry
Central nervous system
High-performance liquid chromatography
Mass to charge ratio
Multiple reaction monitoring
Neurokinin 1 receptor
Neurokinin 2 receptor
Transient receptor potential vanilloid 1
This work was funded by the National Sciences and Engineering Research Council of Canada (F. Beaudry NSERC Discovery grant No. 386637-2010). F. Pailleux received a scholarship from the Coopération et mobilité Internationales Rhône-Alpes (CMIRA).
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