Oxaliplatin induces acute neuropathy within a few hours post-treatment, with symptoms
persisting for several days. Delayed onset muscle soreness also causes the delayed
onset of mechanical pain sensation starting at about 6–8 h and lasting up to a week
after exercise. Both conditions come with impaired proprioception and could be chronic
if these bouts are repeated frequently. The involvement of PIEZO2 ion channels, as
the principal mechanosensory channels responsible for proprioception, is theorized
in both conditions as well. The current opinion manuscript is meant to explain how
the minor stretch-related microdamage of PIEZO2 on Type Ia proprioceptive terminals
could explain the aforementioned symptoms of impaired proprioception. This includes
a platinum-induced proton affinity ‘switch’ on these proprioceptive endings with PIEZO2
content, resulting in this being the likely initiating cause. Furthermore, it postulates
how the proton-based ultrafast long-range oscillatory synchronization to the hippocampus
could be impaired due to this microdamage on Type Ia proprioceptive terminals. Finally,
the manuscript provides insight into how the impairment of the PIEZO2-initiated ultrafast
muscle–brain axis may contribute to chemobrain and its associated cognitive and memory
deficits.
