Synergistic regulation of serotonin and opioid signaling contributes to pain insensitivity in Nav1.7 knockout mice.

ABSTRACT: Genetic loss of the voltage-gated sodium channel Na_v1.7 (Na_v1.7^-/-) results in lifelong insensitivity to pain in mice and humans. One underlying cause is an increase in the production of endogenous opioids in sensory neurons. We analyzed whether Na_v1.7 deficiency altered nociceptive heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) signaling, such as initiated by GPCRs that respond to serotonin (pronociceptive) or opioids (antinociceptive), in sensory neurons. We found that the nociceptive neurons of Na_v1.7 knockout (Na_v1.7^-/-) mice, but not those of Na_v1.8 knockout (Na_v1.8^-/-) mice, exhibited decreased pronociceptive serotonergic signaling through the 5-HT<

SUBMITTER: Isensee J 

PROVIDER: S-EPMC6711404 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature