PIEZO channels are mechanical force sensors involved in various biological processes,
including somatosensation. To date, only a few PIEZO-binding
partners have been identified,
including MyoD-family
inhibitor proteins (MDFI and MDFIC). Here, we show
that MDFIC2, a third member of the MDFI protein family with an as-yet-
unknown
function, is expressed in a subset of nociceptive sensory neurons. MDFIC2 modulates
both PIEZO1 and PIEZO2 gating properties by slowing their kinetics and shifting
mechanical sensitivity to higher forces. Interestingly, Mdfic2 is downregulated in
mouse neuropathic pain models in which mechanical allodynia is a hallmark symptom.
We found that intrathecal administration of adeno-associated
virus vector encoding
MDFIC2 cDNA reduces mechanical sensitivity and attenuates mechanical allodynia in
the spared nerve injury neuropathic pain model. These findings demonstrate a mechanism
for regulating mechanosensation and highlight a potential therapeutic route for
treating mechanical allodynia.