Accelerating the resolution of inflammation in a natural way

Compared with other injuries to the locomotor system, muscle injuries are often neglected. However, retaliation can be quick: Without proper care the affected persons are partially incapacitated for weeks; they are also at increased risk of injuring themselves again. The resolution of inflammation is essential for regeneration. A natural remedy can aid this process. “The trivialization of muscle injuries is problematic,” says Prof. Dr. Anja Hirschmüller, senior physician at the ALTIUS Swiss Sportmed Center in Rheinfelden, Switzerland. She arrived at this insight in the course of her years of work with recreational and competitive athletes, during which she saw many musculoskeletal injuries. In professional soccer approximately 35% of all traumas are muscle injuries; in other disciplines the frequency lies between 10% and 55%, depending on the type of sport. What’s more, about one-third of athletes with muscle injuries are unable to participate in their sport for more than 4 weeks. Decisive for the prognosis are – among other things – the size and type of injury. For instance, direct muscle injuries such as contusions or lacerations, which occur mainly during contact sports such as handball or ice hockey, are basically easier to treat and heal relatively quickly. In contrast, indirect muscle injuries, which frequently occur during running sports such as track and field or soccer, are associated with more protracted regeneration and a higher risk of recurrence. “In addition, it is important when making a prognosis to take note of whether central tendons are also injured. On the one hand, tendons have a worse regeneration potential than muscles; on the other, the neuromuscular activation is more difficult to restore when tendons are involved,” explained Hirschmüller. Further risk factors for recurring injury are, among others, advanced age, beginning again too early, greater body weight, small size, and the localization and size of the injury. Also discussed are pelvic tilt, root irritations of the lumbar spine, or muscle imbalances, reported the sports physician. Imaging is essential Anamnesis is “a very important factor” for clinical diagnosis, stressed Hirschmüller. It is possible to infer the severity of the injury alone from the athlete’s description of the pain. Palpation of the muscles also delivers important clues. Nonetheless, diagnostic imaging is indispensable. This involves an exact classification of the muscle injury as a basis for further therapy and the prognosis. “With ultrasound, structural damage such as a hematoma or a seroma can be detected quickly,” said Hirschmüller. MRI is more sensitive for small injuries, but it is not always available because of the cost. According to Hirschmüller, muscle injuries proceed in stages that influence one another. At the beginning is the degeneration stage, marked by autophagy and apoptosis. This is followed by the stages of inflammation and regeneration. The individual processes do not take place consecutively but rather overlap in time. Thus processes of inflammation characterize both the acute stage and the recovery. Regeneration begins as early as the second day and takes approximately 3 weeks, or longer for large injuries, explained Hirschmüller. Act quickly Above all, the initial therapy is important for the healing process. “Every minute counts,” stressed Hirschmüller. By initially following the RICE rule (rest, ice, compression, elevation), with maximal compression and cooling for 20–30 minutes, a hematoma and dehiscence can be limited as far as possible. Immobilization and nonsteroidal anti-inflammatory drugs (NSAID) should be used for only a short time to relieve pain. Hematomas should be punctured early under the guidance of ultrasound, ideally within the first 36 hours, said Hirschmüller. Infiltrations can also be considered for muscle injuries, with, among others, a natural remedy that contains 14 herbal and mineral agents (Traumeel® S [Tr14]). The natural remedy causes a reduction of the inflammatory activity by stimulating growth factor TGF-𝛃 [1, 2]. Moreover, it was shown in an animal model that, together with a hemoderivative, Tr14 increases the markers for muscle cell regeneration and histologically accelerates muscle healing [3, 4]. Cortisone injections have meanwhile become obsolete, because they can cause muscle necrosis, explained Hirschmüller. Resolution of the inflammation At the center of basic research on inflammations and their inhibition or resolution with natural substances are lipid mediators, which are involved in all phases of inflammation, reported Prof. Dr. Oliver Werz from the Department of Pharmaceutical/Medicinal Chemistry of the University of Jena. “You can think of inflammation as a burst water pipe. With NSAID we turn off the faucet, so to speak. Nevertheless, the room is still under water. In order to restore the normal state, the room must then be drained and cleaned up,” explained Werz. According to the scientist, this applies similarly to the restoration of homeostasis via inflammation resolution. The resolution of inflammation is induced by means of a shift (lipid mediator class switching) from proinflammatory messenger substances to resolution-promoting messenger substances, explained Werz. This follows the acute phase of inflammation and ensures that inflammation-promoting signals are ended and cellular debris is removed. According to recent findings, Werz said, the resolution of inflammation is an actively controlled process with the participation of certain messenger substances that promote healing and restore the homeostasis [5]. These messenger substances are referred to as specialized pro-resolving mediators (SPMs). They include, among others, lipoxins, resolvins, maresins and protectins. Increased production of resolvins In two established and standardized inflammation models, researchers in Werz’s working group investigated whether Tr14 can induce the lipid mediator class switching necessary for the resolution of inflammation. In a mouse model, Tr14 or vehicle (0.9% NaCl) was administered daily for a period of 6 days, prophylactically before or therapeutically 4 and 8 hours after zymosan-induced peritonitis. The exudate was examined 4, 8 and 24 hours after the prophylactic administration and 8 and 24 hours as well as 8 and 15 days after the therapeutic administration. In a human macrophage model, Tr14 or vehicle (0.9% NaCl) was applied to naïve human macrophages differentiated from monocytes (MDM) for 15 minutes. Polarization of the cells to M1 or M2 macrophages was followed by incubation with S. aureus for 180 minutes, and then by an examination of the cell culture supernatant. The result was that, following therapeutic administration for zymosan-induced peritonitis, compared with the control group with vehicle, Tr14 significantly increased the production of resolvins, both in the early phase (after 24 h; p<0.05) and in the late phase of inflammation resolution (after 15 days; p<0.01) [6]. Tr14 shortened the resolution interval (Ri) of the inflammation by 5.9 hours compared with vehicle following prophylactic administration for zymosan-induced peritonitis (Fig. 1) [6]. Tr14 expedites the inflammation resolution by reducing the infiltration of neutrophils in vivo and by accelerating neutrophil apoptosis and enhancing efferocytosis (phagocytosis of apoptotic neutrophils). Moreover, an increase in anti-inflammatory cytokines and SPMs was shown (Fig. 2) [6]. Fig. 1. Tr14 shortens the resolution interval of inflammation (mouse model; modified from [6]) Springer Medizin Verlag GmbH × Fig. 2. Tr14 increased the SPM production as compared with COX-induced pro-inflammatory mediators (mouse model; modified from [6]) Springer Medizin Verlag GmbH × The resolution of inflammation is triggered by a transition from pro-inflammatory to dissolving mediators, summarized Werz. Thus SPMs suppress pro-inflammatory cytokines, inhibit an excessive neutrophil influx, improve phagocytosis, stimulate efferocytosis, promote wound healing and tissue regeneration, and lead to pain relief, explained Werz. This is not possible with NSAID because, according to Werz: “Inflammation blockers inhibit the formation of these mediators, which are also responsible for cleaning up.” In brief Inflammatory processes accompany the entire healing process in muscle injuries. Modern inflammation research no longer deals with the inhibition of inflammation but rather with the question of how the resolution can be promoted. Important processes of inflammation resolution are the reduction of neutrophil influx, the phagocytosis of apoptotic neutrophils by macrophages (efferocytosis), the conversion from M1 to M2 macrophages, and the lipid mediator class switching (from COX products to SPMs). Tr14 strengthens efferocytosis, stimulates the production of SPMs and anti-inflammatory cytokines, and shortens the resolution interval of the inflammation. Tr14 is included in the list of permitted medications issued by the German National Anti-Doping Agency (NADA) [7]. References Heine et al., Biomed Ther 1998, 16:224–226 Porozov S et al., Clin Dev Immunol 2004, 11:143–149 Langendorf EK et al., Int J Sports Med 2019, 40:803–809 Belikan P et al., Int J Mol Sci 2020, 21:2112 Gasteiger G et al., J Innate Immun 2017, 9:111–125 Jordan PM et al., Pharmaceuticals 2021, 14:1123 https://www.nada.de/fileadmin/nada/SERVICE/Downloads/Listen/NADA_Beispielliste_zulaessiger_Medikamente_2022.pdf (letzter Zugriff :18.11.2022) Impressum Lunch Symposium „Musculoskeletal Injuries in Recreational and Competitive Sports – What is the role of inflammation?” on the occasion of the German Congress of Orthopedics and Trauma Surgery (DKOU) Berlin, October 28, 2022 Report: Jürgen Stoschek, Geroldsgrün Medizin Report aktuell No. 516671 printed in: Orthopädie und Unfallchirurgie: Mitteilungen und Nachrichten 1/2023 With the friendly support of Heel GmbH, Baden-Baden Corporate Publishing (responsible in the sense of § 55 Abs. 2 RStV): Ulrike Hafner, Tiergartenstraße 17, 69121 Heidelberg Editor: Andrea Krahnert Springer Medizin Verlag GmbH Heidelberger Platz 3 14197 Berlin Tel: 0800 7780 777 (free of charge within Germany) | +49 (0) 30 827 875 566 Fax: +49 (0) 30 827 875 570 E-Mail: kundenservice@springermedizin.de Springer Medizin Verlag GmbH is part of the publishing group Springer Nature Executive Board: Fabian Kaufmann, Dr. Cécile Mack, Dr. Hendrik Pugge Commercial Register of the Local Court of Berlin-Charlottenburg HRB 167094 B VAT number: DE 230026696 © Springer Medizin Verlag GmbH Die Wiedergabe von Gebrauchsnamen, Handelsnamen, Warenbezeichnungen usw. berechtigt auch ohne besondere Kennzeichnung nicht zu der Annahme, dass solche Namen im Sinne der Warenzeichen- und Markenschutz-Gesetzgebung als frei zu betrachten wären und daher von jedermann benutzt werden dürfen. 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