Peripheral pain mechanisms.

Our understanding of the cellular and molecular bases of transduction of painful stimuli has burgeoned in the past year, mainly as a result of studies on isolated sensory neurones in culture. The ion channels underlying neuronal responses to noxious heat, to protons and to ATP have recently been characterized. The typical increase in nociceptor sensitivity produced by tissue damage has been found to be mediated by at least two distinct mechanisms. In the first, bradykinin augments the current activated by heat through a mechanism that involves activation of protein kinase C. In a second sensitization mechanism, prostaglandin E2 alters the voltage threshold of several ion channels, including a novel tetrodotoxin-insensitive Na+ channel, in such a way that initiation of action potentials is facilitated.