The Centers for Disease Control and Prevention estimates that chronic pain impacts one out of every five Americans. While chronic pain remains a broad concept, it can be debilitating. Many causes of chronic pain exist; however, for many conditions, the mechanisms that underlie feelings of pain are still not well understood. As such, it is important to study the molecular underpinnings of what causes pain, specifically nociceptors.
Nociceptors, generated from cells in the dorsal root ganglion (DRG), are specialized sensory receptors that detect pain. The DRG is a grouping of neurons that transmits sensory information to the brain for processing and perception thus making nociceptors an appropriate target for the study of pain in order to better identity the mechanisms behind as well as treatments for chronic pain.
Nociceptors enter the skin to detect painful stimuli.
Image source: MedicalRF.com
Nociceptor neurons — like every other cell — are given instructions by DNA, which gets transcribed into RNA to instruct proteins that provide the tools for the cell to operate. How much RNA or protein gets expressed can drastically change how a cell functions. With this understanding, authors of a recent paper published in Science Translational Medicine have built an RNA map of human nociceptor cells. They identified 12 subtypes of nociceptors across the DRG along with the type of ion channels that the cells use. These different subtypes are responsible for detecting different types of pain, such as heat or mechanical-based pain. Subsequently, this enables researchers to better identify different drug targets for chronic pain treatment.
Additionally, the researchers identified sex-based differences in the RNA profiles from the DRG donors they used in the study. In female donor nociceptors, the authors found increased expression of CALCA, a gene that impacts multiple processes related to hormones and calcium. The effect of this is currently not well understood, as more research is required to understand how this impacts broader symptoms of pain. Overall, this work provides a more extensive understanding of how human nociceptors work, which can, in turn, be used to better understand how pain is presented in patients with chronic pain in an effort to treat chronic pain altogether.
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