 It appears that complete inactivation of Nav 1.7-mediated sodium efflux is necessary to upregulate enkephalin expression enough to achieve complete analgesia.Prior to the development of JNJ63955, the most potent [Nav 1.7] antagonists had failed in regards to achieving the same degree of analgesia as congenital Nav 1.7 inactivity.The proposed mechanism also suggests that the analgesic effects of Nav1.7 blockers may be greatly potentiated by the co-administration of exogenous opioids or enkephalinase inhibitors.