Nociceptive neurons generate trains of action potentials in response to painful stimuli, and the frequency of firing signals the intensity of the pain. Pro-inflammatory mediators such as prostaglandin E ₂ (PGE₂) enhance the sensation of pain by increasing the frequency of action potential firing in response to a given level of painful stimulus. The mechanism by which the firing frequency is enhanced is discussed in the present review. One hypothesis proposes that the threshold for action potential initiation is lowered because the activation curve of a nociceptor-specific voltage-activated Na current, Na_V1.8, is shifted to more negative values by PGE₂. Recent measurements in our lab show, however, that the action potential threshold in fact changes little when AP firing is accelerated by PGE₂. The enhanced firing is, however, abolished by a blocker of an inward current activated by hyperpolarisation, called I _h. The voltage sensitivity of I _h shifts in the positive direction in small nociceptive neurons when they are exposed to pro-inflammatory mediators, such as PGE₂, which activate adenylate cyclase and therefore increase levels of cAMP. By this mechanism the inward current between the resting membrane potential and the threshold for firing of action potentials is enhanced, and the rate of depolarisation in the interval between action potentials is therefore increased. We conclude that the major mechanism responsible for increasing action potential firing following tissue damage or metabolic stress is the hyperpolarisation-activated inward current, I _h, and that other mechanisms play at most a minor role.