Local Translation in Primary Afferents and Its Contribution to Pain.

ABSTRACT:Chronic pain remains a significant problem due to its prevalence, impact, and limited therapeutic options. Progress in addressing chronic pain is dependent on a better understanding of underlying mechanisms. Although the available evidence suggests that changes within the central nervous system contribute to the initiation and maintenance of chronic pain, it also suggests that the primary afferent plays a critical role in all phases of the manifestation of chronic pain in most of those who suffer. Most notable among the changes in primary afferents is an increase in excitability or sensitization. A number of mechanisms have been identified that contribute to primary afferent sensitization with evidence for both increases in pronociceptive signaling molecules, such as voltage-gated sodium channels, and decreases in antinociceptive signaling molecules, such as voltage-dependent or calcium-dependent potassium channels. Furthermore, these changes in signaling molecules seem to reflect changes in gene expression as well as posttranslational processing. A mechanism of sensitization that has received far less attention, however, is the local or axonal translation of these signaling molecules. A growing body of evidence indicates that this process not only is dynamically regulated but also contributes to the initiation and maintenance of chronic pain. Here, we review the biology of local translation in primary afferents and its relevance to pain pathobiology.