Journal
PLOS ONE
Volume 11, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0152405
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Funding
- Biotechnology and Biological Sciences Research Council [1099809] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [1099809] Funding Source: researchfish
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Human genetic studies show that the voltage gated sodium channel 1.7 (Na(v)1.7) is a key molecular determinant of pain sensation. However, defining the Na(v)1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Na(v)1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Na(v)1.7's role in nociceptor physiology. We report that Na(v)1.7 is the predominant functional TTX-sensitive Na-v in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Na(v)1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Na(v)1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission.
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