Translating nociceptor sensitivity: the role of axonal protein synthesis in nociceptor physiology.
The increased sensitivity of peripheral pain-sensing neurons, or nociceptors, is a major cause of the sensation of pain that follows injury. This plasticity is thought to contribute to the maintenance of chronic pain states. Although we have a broad knowledge of the factors that stimulate changes in nociceptor sensitivity, the cellular mechanisms that underlie this plasticity are still poorly understood; however, they are likely to involve changes in gene expression required for the phenotypic and functional changes seen in nociceptive neurons after injury. While the regulation of gene expression at the transcriptional level has been studied extensively, the regulation of protein synthesis, which is also a tightly controlled process, has only recently received more attention. Despite the established role of protein synthesis in the plasticity of neuronal cell bodies and dendrites, little attention has been paid to the role of translation control in mature undamaged axons. In this regard, several recent studies have demonstrated that the control of protein synthesis within the axonal compartment is crucial for the normal function and regulation of sensitivity of nociceptors. Pathways and proteins regulating this process, such as the mammalian target of rapamycin signaling cascade and the fragile X mental retardation protein, have recently been identified. We review here recent evidence for the regulation of protein synthesis within a nociceptor's axonal compartment and its contribution to this neuron's plasticity. We believe that an increased understanding of this process will lead to the identification of novel targets for the treatment of chronic pain.
Price
Theodore J
TJ
The University of Arizona, School of Medicine, Department of Pharmacology, 1501 N Campbell Ave, Tucson, AZ 85724, USA. tjprice@email.arizona.edu
Géranton
Sandrine M
SM
D001369:Axons / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology
D009419:Nerve Tissue Proteins