medicines Review Clinical Trials, Potential Mechanisms, and Adverse Effects of Arnica as an Adjunct Medication for Pain Management Amanda G. Smith 1 , Victoria N. Miles 1 , Deltrice T. Holmes 2 , Xin Chen 3 and Wei Lei 1, *   Citation: Smith, A.G.; Miles, V.N.; Holmes, D.T.; Chen, X.; Lei, W. Clinical Trials, Potential Mechanisms, and Adverse Effects of Arnica as an Adjunct Medication for Pain Management. Medicines 2021, 8, 58. https://doi.org/10.3390/medicines 8100058 Academic Editor: William Cho Received: 23 August 2021 Accepted: 2 October 2021 Published: 9 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 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 (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC 29325, USA; agsmith@presby.edu (A.G.S.); vnmiles@presby.edu (V.N.M.) 2 Department of Biology, College of Art and Sciences, Presbyterian College, Clinton, SC 29325, USA; dtholmes@presby.edu 3 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA; xchen@campbell.edu * Correspondence: wlei@presby.edu; Tel.: +1-(864)-938-3836 Abstract: Arnica has traditionally been used in treating numerous medical conditions, including inflammation and pain. This review aims to summarize the results of studies testing Arnica products for pain management under different conditions, including post-operation, arthritis, low back pain, and other types of musculoskeletal pain. Based on data from clinical trials, Arnica extract or gel/cream containing Arnica extract shows promising effects for pain relief. These medical benefits of Arnica may be attributed to its chemical components, with demonstrated anti-inflammatory, antioxidant, anti-microbial, and other biological activities. In conclusion, Arnica could be an adjunct therapeutical approach for acute and chronic pain management. Keywords: Arnica; pain; herbal medication; alternative therapy; inflammation 1. Introduction Pain is a serious health concern and affects more than 100 million people in the United States [1]. Pain reduces the quality of life of patients, and treatment of pain is costly [2]. There are various underlying pathologies associated with pain, such as comorbid conditions, injury, medical treatment, inflammation, neuropathy, and idiopathic pain [2]. It is widely accepted that chronic pain results from a complex interaction of physiological, psychological, and social influences [3]. The multi-faceted nature of pain complicates strategies for management [3]. Further still, the most widely utilized treatment options, such as non-steroidal anti-inflammatory drugs and opioid analgesics, show clinical efficacy in relieving pain; however, the adverse effects associated with those medications limit their use for pain management [4]. Therefore, discovering alternative therapies for pain management is in high demanded. Arnica belongs to the Asteraceae family, a group of flowering plants containing several well-known members, such as marigold, daisy, and chamomile [5]. Arnica has been used in traditional and homeopathic medicine for centuries in Europe and North America [6]. Multiple species within this genus have been documented and studied for medical potential. A. montana and A. chamissons are native to Europe, while A. acaulis, A. cordifolia, A. fulgens, and A. sororia are native to North America [7]. Many species are used in homeopathic and traditional medicine practices, although A. montana is the most commonly used species in commercially produced products [8]. Arnica has been used in homeopathic medicine for centuries for dozens of pathological conditions, including joint and muscle pain, inflammation, and arthritis [8]. Arnica has various pharmacologic activities, including anti-inflammatory, analgesic, anti-microbial, antirheumatic, antiarthritic, and antineoplastic activities [9]. Although Arnica is still used for these alternate indications, ingestible formulations are not utilized in modern therapies Medicines 2021, 8, 58. https://doi.org/10.3390/medicines8100058 https://www.mdpi.com/journal/medicines