The activation of peripheral nociceptors is the subject of intense scr
utiny, because of its significance in pain regulation, Genetic approac
hes, including homology cloning, difference cloning and transgenic man
ipulation of mice are providing useful insights into nociceptor functi
on, Recent work suggests that transcriptional regulators (for example,
islet-I), which are expressed relatively selectively in sensory neuro
nes, play a crucial role in defining cellular phenotype. Difference cl
oning has identified genes which encode both ligand-gated and voltage-
gated ion channels expressed by small-diameter sensory neurones. The r
ole of inflammatory mediators such as NGF in regulating nociceptor fun
ction has been clarified in mis-expression and deletion studies,An und
erstanding of the mechanisms that regulate gene expression in nocicept
ors should provide new ways to manipulate nociceptor sensitivity, with
potential significance for pain therapy.