biostudies-literatureIseppon FCancer Research UKVersus ArthritisNIHR Cambridge Biomedical Research CentreMedical Research CouncilUK Research and Innovation Medical Research CouncilWellcome Trust100168https://www.ebi.ac.uk/biostudies/studies/S-EPMC11570969biostudies-literatureUnknown16Genetic 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. AduNeurobiology of pain (Cambridge, Mass.)Sodium channels Na<sub>v</sub>1.7, Na<sub>v</sub>1.8 and pain; two distinct mechanisms for Na<sub>v</sub>1.7 null analgesia.PMC1157096921950221521/Z/20/Z185341571476MR/V012509/1Kanellopoulos AHWood JNWoods CGCaan GThalassinos KCubuk CLewis MJCox JJChiozzi RTian NIseppon FZhao JZhou JfalseSodium channels Na<sub>v</sub>1.7, Na<sub>v</sub>1.8 and pain; two distinct mechanisms for Na<sub>v</sub>1.7 null analgesia.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. Adu2024-01-01T00:00:00Z2024 Jul-Dec2026-05-26T20:11:34.978Z2025-04-21T21:43:10.034ZS-EPMC115709693955975210.1016/j.ynpai.2024.100168