Loss-of-function mutations in the SCN9A gene encoding voltage-gated sodium channel Nav1.7 cause congenital insensitivity to pain in humans and mice. Surprisingly, many potent selective antagonists of Nav1.7 are weak analgesics.
Scientists investigated whether Nav1.7, as well as contributing to electrical signalling, may have additional functions. They report in the journal Nature Communications that Nav1.7 deletion has profound effects on gene expression, leading to an upregulation of enkephalin precursor Penk mRNA and met-enkephalin protein in sensory neurons.
In contrast, Nav1.8-null mutant sensory neurons show no upregulated Penk mRNA expression.
Application of the opioid antagonist naloxone potentiates noxious peripheral input into the spinal cord and dramatically reduces analgesia in both female and male Nav1.7-null mutant mice, as well as in a human Nav1.7-null mutant.
These data suggest that Nav1.7 channel blockers alone may not replicate the analgesic phenotype of null mutant humans and mice, but may be potentiated with exogenous opioids.
http://www.nature.com/ncomms/2015/151204/ncomms9967/full/ncomms9967.html
Edited
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