Inflammation-Mediated Hyperexcitability of Sensory Neurons

One of the most prominent signs of tissue injury and inflammation is pain and pain continues to be the primary reason people seek medical attention. Inflammatory pain reflects, at least in part, an increase in the excitability, or sensitization, of subpopulations of primary afferent neurons. While the sensitization of high threshold afferents was observed almost 40 years ago, the basis for this phenomenon continues to be an active and fertile area of research today. This review will summarize recent advances in our mechanistic understanding of sensitization, focusing on four general areas where re search has been most active or productive. These include: (1) the characterization of second messenger pathways underlying inflammation-induced changes in afferent excitability; (2) the impact of previous injury on the afferent response to subsequent inflammation; (3) the impact of target of innervation on the specific afferent response to inflammation, and (4) the impact of sex hormones on the sensitization of high threshold afferents. Work in these areas highlights how much has been learned about this process as well as how much there is yet to learn.