In inflammation, non-neuronal cells produce a variety of chemical mediators that act on nociceptive neurones. Ultimately, the discharge of these neurones is controlled by the activity of membrane ion channels. Some chemical mediators (e.g. ATP, protons, 5-hydroxytryptamine) act on receptors that are linked directly to ion channels. Other mediators (e.g. bradykinin) act indirectly through receptors linked to second messenger systems and in this way modulate the activity of ion channels and either activate or sensitize the neurones. The eicosanoids, which are produced by a variety of cell types, have important intra- and inter-cellular roles in nociception. The interactions between neurones and non-neuronal cells are likely to be complex as some types of non-neuronal cells express receptors for sensory neuropeptides (substance P). Recent studies also suggest that cytokines and growth factors can have long term effects on nociceptive neurone function.