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      Spinal Reactive Oxygen Species and Oxidative Damage Mediate Chronic Pain in Lame Dairy Cows

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          Abstract

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          Chronic inflammatory diseases could impact central nervous system homeostasis, being oxidative damage of the dorsal horn, a relevant mechanism mediating central sensitization. Chronic inflammatory lameness in dairy cows is a painful condition that affects animal welfare, affecting dairy production worldwide. This study reveals increased levels of reactive oxygen species, malondialdehyde, and carbonyl groups, indicating lipid and protein damage in the spinal cord of cows with chronic lameness. Moreover, antioxidant system activity was similar between lame and non-lame cows which suggests that antioxidant dysregulation was not the cause of oxidative damage, as has been proposed previously. Based on the fact that nociceptive pathways are strongly conserved between species, there is no reason to neglect that chronic pain in cows promotes Central Nervous System (CNS) alterations, such as oxidative damage. Moreover, lame cows develop central sensitization, as allodynia and hyperalgesia are centrally and not peripherally mediated. Our results support the current assumption that chronic pain is a central nervous system disease and lameness in dairy cows is far beyond an inflammation of the hoof.

          Abstract

          Lameness in dairy cows is a worldwide prevalent disease with a negative impact on animal welfare and herd economy. Oxidative damage and antioxidant system dysfunction are common features of many CNS diseases, including chronic pain. The aim of this study was to evaluate the levels of reactive oxygen species (ROS) and oxidative damage markers in the spinal cord of dairy cows with chronic inflammatory lameness. Locomotion score was performed in order to select cows with chronic lameness. Dorsal horn spinal cord samples were obtained post mortem from lumbar segments (L2–L5), and ROS, malondialdehyde (MDA), and carbonyl groups were measured along with the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant response (TAR). Lame cows had increased levels of ROS, MDA, and carbonyl groups, while no differences were observed between lame and non-lame cows in SOD, GPx, CAT, and TAR activity. We conclude that painful chronic inflammatory lameness in dairy cows is associated with an increase in ROS, MDA, and carbonyl groups. Nonetheless, an association between ROS generation and dysfunction of the antioxidant system, as previously proposed, could not be established.

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          Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease.

          The endoplasmic reticulum (ER) is a specialized organelle for the folding and trafficking of proteins, which is highly sensitive to changes in intracellular homeostasis and extracellular stimuli. Alterations in the protein-folding environment cause accumulation of misfolded proteins in the ER that profoundly affect a variety of cellular signaling processes, including reduction-oxidation (redox) homeostasis, energy production, inflammation, differentiation, and apoptosis. The unfolded protein response (UPR) is a collection of adaptive signaling pathways that evolved to resolve protein misfolding and restore an efficient protein-folding environment. Production of reactive oxygen species (ROS) has been linked to ER stress and the UPR. ROS play a critical role in many cellular processes and can be produced in the cytosol and several organelles, including the ER and mitochondria. Studies suggest that altered redox homeostasis in the ER is sufficient to cause ER stress, which could, in turn, induce the production of ROS in the ER and mitochondria. Although ER stress and oxidative stress coexist in many pathologic states, whether and how these stresses interact is unknown. It is also unclear how changes in the protein-folding environment in the ER cause oxidative stress. In addition, how ROS production and protein misfolding commit the cell to an apoptotic death and contribute to various degenerative diseases is unknown. A greater fundamental understanding of the mechanisms that preserve protein folding homeostasis and redox status will provide new information toward the development of novel therapeutics for many human diseases.
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            A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly

            NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly.
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              Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects.

              Chemical probes for free radicals in biology are important tools; fluorescence and chemiluminescence offer high detection sensitivity. This article reviews progress in the development of probes for "reactive oxygen and nitrogen" species, emphasizing the caution needed in their use. Reactive species include hydrogen peroxide; hydroxyl, superoxide, and thiyl radicals; carbonate radical-anion; and nitric oxide, nitrogen dioxide, and peroxynitrite. Probes based on reduced dyes lack selectivity and may require a catalyst for reaction: despite these drawbacks, dichlorodihydrofluorescein and dihydrorhodamine have been used in well over 2,000 studies. Use in cellular systems requires loading into cells, and minimizing leakage. Reactive species can compete with intracellular antioxidants, changes in fluorescence or luminescence possibly reflecting changes in competing antioxidants rather than free radical generation rate. Products being measured can react further with radicals, and intermediate probe radicals are often reactive toward antioxidants and especially oxygen, to generate superoxide. Common probes for superoxide and nitric oxide require activation to a reactive intermediate; activation is not achieved by the radical of interest and the response is thus additionally sensitive to this first step. Rational use of probes requires understanding and quantitation of the mechanistic pathways involved, and of environmental factors such as oxygen and pH. We can build on this framework of knowledge in evaluating new probes.
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                Author and article information

                Journal
                Animals (Basel)
                Animals (Basel)
                animals
                Animals : an Open Access Journal from MDPI
                MDPI
                2076-2615
                17 September 2019
                September 2019
                : 9
                : 9
                : 693
                Affiliations
                [1 ]Graduate School, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5110566, Chile; danielherzberg@ 123456gmail.com (D.H.); heine.jakob@ 123456gmail.com (H.M.)
                [2 ]Animal Science Institute, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5110566, Chile; pablostrobel@ 123456uach.cl (P.S.); alfredoramirez@ 123456uach.cl (A.R.-R.); marianne.werner@ 123456uach.cl (M.W.)
                [3 ]Department of Veterinary Sciences, Universidad Católica de Temuco, Temuco 4780000, Chile; rchihuailaf@ 123456uct.cl
                [4 ]Veterinary Clinical Sciences Institute, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5110566, Chile
                Author notes
                [* ]Correspondence: hbustamante@ 123456uach.cl ; Tel.: +56-632221077
                Article
                animals-09-00693
                10.3390/ani9090693
                6770087
                31533257
                2648ac9f-a746-458c-a705-78f71b23d2b5
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 August 2019
                : 14 September 2019
                Categories
                Article

                bovine,lameness,chronic pain,oxidative stress
                bovine, lameness, chronic pain, oxidative stress

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