Furthermore, loss-of-function mutations in NaV1.7 do not consistently reduce nociceptor excitability (see Discussion) and the associated insensitivity to pain involves increased opioid signaling (MacDonald et al., 2021; Minett et al., 2015), consistent with naloxone’s ability to restore pain sensitivity in CIP patients (MacDonald et al., 2021; Dehen et al., 1978). Here, SCN9A is linked to hereditary sensory and autonomic neuropathy.