▁being ▁contrib ut ory ▁factors ) ". ▁A ▁gain - of - function ▁mut ation ▁in ▁the ▁fourth ▁transm emb rane ▁domain ▁causes ▁the ▁channel ▁to ▁be ▁over ly ▁sensitive ▁to ▁ph arm ac ological ▁activation . ▁ ▁Met abol ites ▁of ▁par ac et am ol ▁( ac et amin oph en ) ▁have ▁been ▁demonstrated ▁to ▁bind ▁to ▁the ▁TR PA 1 ▁re cept ors ▁( pro bably ▁ag on ism ▁which ▁then ▁can ▁lead ▁to ▁des ens it ization ▁of ▁TR PA 1 ▁re cept ors ▁in ▁the ▁way ▁that ▁cap sa ic in ▁does ▁it ▁in ▁the ▁sp inal ▁cord ▁of ▁m ice , ▁causing ▁an ▁ant in oc ice pt ive ▁effect . ▁This ▁is ▁suggested ▁as ▁the ▁ant in oc ice pt ive ▁mechanism ▁for ▁par ac et am ol . ▁ ▁Ox al ate , ▁a ▁met abol ite ▁of ▁an ▁anti ▁cancer ▁drug ▁ox ali pl atin , ▁has ▁been ▁demonstrated ▁to ▁in hib it ▁pro ly l ▁hydro x yl ase , ▁which ▁end ows ▁cold - ins ens itive ▁human ▁TR PA 1 ▁with ▁pseudo ▁cold ▁sens itivity ▁( via ▁re active ▁o xygen ▁generation ▁from ▁mit och ond ria ). ▁This ▁may ▁cause ▁a ▁characteristic ▁side - effect ▁of ▁ox ali pl atin ▁( c old - trigger ed ▁ac ute ▁peri pher al ▁ne urop ath y ). ▁ ▁Lig and ▁binding ▁TR PA 1 ▁can ▁be ▁considered ▁to ▁be ▁one ▁of ▁the ▁most ▁prom is cu ous ▁TR P ▁ion