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. While 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 the majority 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 pro-nociceptive signaling molecules such as voltage-gated sodium channels, as well as decreases in anti-nociceptive signaling molecules such as voltage- or calcium-dependent potassium channels. Furthermore, these changes in signaling molecules appear to reflect changes in gene expression as well as post-translational 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 is not only 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.