Sodium channels Na_v1.7, Na_v1.8 and pain; two distinct mechanisms for Na_v1.7 null analgesia.

ABSTRACT: Genetic deletion and pharmacological inhibition are distinct approaches to unravelling pain mechanisms, identifying targets and developing new analgesics. Both approaches have been applied to the voltage-gated sodium channels Na_v1.7 and Na_v1.8. Genetic deletion of Na_v1.8 in mice leads to a loss of pain and antagonists are effective analgesics. The situation with Nav1.7 is more complex. Complete embryonic loss of Na_v1.7 in humans or in mouse sensory neurons leads to anosmia as well as profound analgesia as a result of diminished neurotransmitter release. This is mediated by enhanced endogenous opioid signaling in humans and mice. In contrast, anosmia is opioid-independent. Sensory neuron excitability and autonomic function appear to be normal. Adu

SUBMITTER: Iseppon F 

PROVIDER: S-EPMC11570969 | biostudies-literature | 2024 Jul-Dec

REPOSITORIES: biostudies-literature