The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways

Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-ga ted sodium channels. Here we examined the role of the sensory-neuron-specif ic (SNS) TTX-resistant sodium channel a subunit in nociception and pain by constructing sns-null mutant mice. These mice expressed only TTX-sensitive sodium currents on step depolarizations from normal resting potentials, sho wing that all slow TTX-resistant currents are encoded by the sns gene. Null mutants were viable, fertile and apparently normal, although lowered thres holds of electrical activation of C-fibers and increased current densities of TTX-sensitive channels demonstrated compensatory upregulation of TTX-sen sitive currents in sensory neurons. Behavioral studies demonstrated a prono unced analgesia to noxious mechanical stimuli, small deficits in noxious th ermoreception and delayed development of inflammatory hyperalgesia. These d ata show that SNS is involved in pain pathways and suggest that blockade of SNS expression or function may produce analgesia without side effects.