Who is Paulino Barragan-Iglesias?
Paulino Barragan-Iglesias is an assistant professor at the Department of Physiology and Pharmacology, Center for Basic Sciences, Autonomous University of Aguascalientes, Mexico. He received his PhD in Neuropharmacology and Experimental Therapeutics from CINVESTAV in 2014. Then, he moved to the US from 2015 to 2019, where he completed a postdoctoral training in the Pain Neurobiology Research Group at UT-Dallas. His research goal is to understand the mechanisms through which tissue and nerve injury produce nociceptive plasticity leading to persistent pain. His current research includes study of potential therapeutic pain targets using molecular, pharmacological and behavioral methods. Most of his work is concentrated on primary sensory and spinal cord neurons, with special attention in the study of neuroimmune interactions and differential contribution of genes that are expressed in neuronal and glial subpopulations in the dorsal root ganglion. Recently, he has been interested in the study of translation regulation and modulation of axonal transport in primary afferent fibers in response to diabetic-, chemotherapy-, and virus-induced peripheral neuropathies. His final goal is to alleviate the burden of chronic pain through basic research, therapeutic discovery and education.
What is the aim of the program?
The aim of this project is to study how viral infections produce nociceptor plasticity leading to painful states. They recently reported that type I interferons, produced in response to a viral infection, are capable of sensitizing peripheral nociceptors by a mechanism that engages translation regulation signaling. However, the precise mechanism by which viral components activate the nociceptive system remains unknown. In order to investigate the mechanisms underlying virus-evoked pain, we simulated a viral infection in mice by consecutively injecting the synthetic doubled-stranded RNA (dsRNA) Poly I:C (Figure 1A). Poly(I:C) is structurally similar to dsRNA, present in some viruses, and is therefore commonly used to model the cellular actions of dsRNA.
What were your findings?
In male mice, intraperitoneal Poly I:C (henceforth referred to as dsRNA) injection for 5 days produced an increase in core body temperature measured by FLIR imaging and a decrease in body weight that recovered partially 2 weeks later. Effects on body weight and body temperature were accompanied with changes in exploratory behaviors in the open field test. Particularly, we observed a decrease and increase in total distance traveled and immobility time, respectively, in mice injected with dsRNA but not vehicle (saline). In female mice, they only observed an increase in core body temperature in dsRNA-injected mice without any statistically significant changes in body weight or total distance traveled and immobility time in the open field test.
What conclusions can you draw from this?
Their results suggest that dsRNA strongly affects male mice. However, they sought to investigate the effects of dsRNA in pain-like behaviors using both male and female mice. In response to daily dsRNA administration, male and female mice showed a decrease in withdrawal threshold, peaking at day 5, in response to mechanical stimulation with von Frey filaments. They did not observe any differences in the development of mechanical hypersensitivity between male and female mice treated with dsRNA. Unlike mechanical hypersensitivity, thermal and grimace responses were not modify by dsRNA administration in either male or female mice compared to vehicle. As expected, when comparing male vs female mice injected with dsRNA, no statistical differences on thermal and grimace responses were observed. These results demonstrate that dsRNA sensitizes peripheral nociceptive neurons to mechanical stimulation in both male and female mice. These data suggest that PKReIF2a signaling axis play a key role in dsRNA sensing/signaling in nociceptors to promote mechanical pain.
Will a future investigation be needed as a result of the findings?
Based on the strong effects of dsRNA observed in male mice, they decided to further investigate the cellular and molecular mechanism underlying nociceptor sensitization only in males. However, the mechanisms underlying differential changes in body weight and exploratory behaviors in male vs female mice observed in this study are intriguing and; therefore, a future investigation by our lab is warranted.