@article{meneses_gidcumb_marcus_gonzalez_lai_mishra_lascelles_nolan_2023, title={Acute radiotherapy-associated oral pain may promote tumor growth at distant sites}, volume={13}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2023.1029108}, abstractNote={IntroductionPatients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site.}, journal={FRONTIERS IN ONCOLOGY}, author={Meneses, Constanza S. and Gidcumb, Emily M. and Marcus, Karen L. and Gonzalez, Yarines and Lai, Yen Hao and Mishra, Santosh K. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2023}, month={May} } @article{lai_baumer_meneses_roback_robertson_mishra_lascelles_nolan_2021, title={Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of Transient Receptor Potential (TRP) Ion Channels}, volume={196}, ISSN={["1938-5404"]}, DOI={10.1667/RADE-21-000103.1}, abstractNote={Signal transduction at sensory neurons occurs via transmembrane flux of cations, which is largely governed by the transient receptor potential (TRP) family of ion channels. It is unknown whether TRP channel activation contributes to the pain that accompanies radiation-induced oral mucositis. This study sought to characterize changes in TRP channel expression and function that occur in the locally irradiated tissues and afferent neurons of mice. Female CD-1 mice received single high-dose (27 Gy) tongue irradiation, or sham irradiation. Animals were euthanized either before overt glossitis developed (days 1 and 5 postirradiation), when glossitis was severe (day 11), or after mice had recovered (days 21 and 45). Tongue irradiation caused upregulation of the Trpv1 gene in trigeminal ganglia (TG) neurons. Other TRP genes (Trpv2, Trpv4, Trpa1, Trpm8) and Gfrα3 (which acts upstream of several TRP channels) were also upregulated in TGs and/or tongue tissue, in response to radiation. Ex vivo calcium imaging experiments demonstrated that the proportions of TG neurons responding to histamine (an activator of TRPV1, TRPV4 and TRPA1), TNF-α (an activator of TRPV1, TRPV2 and TRPV4), and capsaicin (a TRPV1 agonist), were increased as early as one day after tongue irradiation; these changes persisted for at least 21 days. In a subsequent experiment, we found that genetic deletion of TRPV1 mitigated weight loss (a surrogate marker of pain severity) in mice with severe glossitis. The results intimate that various TRP channels, and TRPV1 in particular, should be explored as analgesic targets for patients experiencing pain after oral irradiation.}, number={4}, journal={RADIATION RESEARCH}, author={Lai, Yen and Baumer, Wolfgang and Meneses, Constanza and Roback, Donald M. and Robertson, James B. and Mishra, Santosh K. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2021}, month={Oct}, pages={331–344} } @article{herzberg_strobel_muller_meneses_werner_bustamante_2020, title={Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness}, volume={15}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0228134}, abstractNote={Chronic lameness affects bovine welfare and has a negative economic impact in dairy industry. Moreover, due to the translational gap between traditional pain models and new drugs development for treating chronic pain states, naturally occurring painful diseases could be a potential translational tool for chronic pain research. We therefore employed liquid chromatography tandem mass spectrometry (LC-MS/MS) to stablish the proteomic profile of the spinal cord samples from lumbar segments (L2-L4) of chronic lame dairy cows. Data were validated and quantified through software tool (Scaffold® v 4.0) using output data from two search engines (SEQUEST® and X-Tandem®). Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis was performed to detect proteins interactions. LC-MS/MS identified a total amount of 177 proteins; of which 129 proteins were able to be quantified. Lame cows showed a strong upregulation of interacting proteins with chaperone and stress functions such as Hsp70 (p < 0.006), Hsc70 (p < 0.0079), Hsp90 (p < 0.015), STIP (p > 0.0018) and Grp78 (p <0.0068), and interacting proteins associated to glycolytic pathway such as; γ-enolase (p < 0.0095), α-enolase (p < 0.013) and hexokinase-1 (p < 0.028). It was not possible to establish a clear network of interaction in several upregulated proteins in lame cows. Non-interacting proteins were mainly associated to redox process and cytoskeletal organization. The most relevant down regulated protein in lame cows was myelin basic protein (MBP) (p < 0.02). Chronic inflammatory lameness in cows is associated to increased expression of stress proteins with chaperone, metabolism, redox and structural functions. A state of endoplasmic reticulum stress and unfolded protein response (UPR) might explain the changes in protein expression in lame cows; however, further studies need to be performed in order to confirm these findings.}, number={1}, journal={PLOS ONE}, author={Herzberg, Daniel and Strobel, Pablo and Muller, Heine and Meneses, Constanza and Werner, Marianne and Bustamante, Hedie}, year={2020}, month={Jan} }