Review Nitric oxide: Is it the cause of muscle soreness? Zsolt Radak a,b,⇑ , Hisashi Naito b , Albert W. Taylor a,c , Sataro Goto b a Semmelweis University, Research Institute of Sport Science, Budapest, Hungary b Department of Exercise Physiology, School of Health and Sport Science, Juntendo University, Chiba, Japan c Faculty of Health Sciences, The University of Western Ontario, London, Canada article info Article history: Received 17 November 2011 Revised 14 December 2011 Available online 28 December 2011 Keywords: Exercise Skeletal muscle Muscle damage Pain Hormesis abstract Skeletal muscle hosts all of the isoforms of nitric oxide synthase (NOS). It is well documented that nitric oxide (NO) regulates force generation and satellite cell activation, and therefore, damage repair of skeletal muscle. NO can also activate nociceptors of C-fibers, thereby causing the sensation of pain. Although delayed-onset of muscle soreness (DOMS) is associated with decreased maximal force generation, pain sensation and sarcomere damage, there is a paucity of research linking NO and DOMS. The present mini-review attempts to elucidate the possible relationship between NO and DOMS, based upon current literature. Ó 2011 Published by Elsevier Inc. Contents Introduction............................................................................................................ 89 Muscle soreness-induced suppression of maximal force generation and the potential role of nitric oxide ................................ 90 Is nitric oxide involved in muscle soreness? .................................................................................. 90 Muscle damage and repair ................................................................................................ 91 Conclusion ............................................................................................................. 92 Perspectives ............................................................................................................ 92 Acknowledgment ...................................................................................................... 92 References ........................................................................................................... 92 Introduction Although, delayed-onset of muscle soreness (DOMS) has been extensively studied, the phenomenon is still not completely under- stood. DOMS peaks about 1–3 days after unaccustomed exercise bouts, the result of lengthening contractions [1,2]. The etiology of DOMS is still vague [3], even after a number of different hypothe- ses have described the most important symptoms, which are, pain, decreased maximal force generation, and altered permeability of sarcolemma. It was suggested long ago, that DOMS is associated with mechanical damage. In 1977 Abraham [4] measured the ratio of hydroxyproline/creatinine in the urine samples of subjects with and without muscle soreness, and the increased ratio indicated sig- nificant damage to connective tissue. From biopsy samples, Friden and co-workers [5,6] reported that DOMS-associated muscle dam- age included intermyofibrillar sarcoma disturbances, and Z-band streaming, especially in Type 2 fibers [7–10]. This observation was confirmed later using magnetic resonance techniques [10,11]. Edema formation has also been observed in subjects suf- fering from DOMS [12]. A large increase in creatine kinase (CK) and myoglobin concentrations in the circulation are two of the most often used associated markers of DOMS and indicate increased permeability of the sarcolemma [13–18]. However, it has been reported that the magnitude of DOMS is not always asso- ciated with the magnitude of other markers of muscle damage [19]. In normal conditions, tissue damage is associated with inflam- mation, which, besides the well known beneficial effects, could also result in some of the discomforts of DOMS [20]. Based upon 1089-8603/$ - see front matter Ó 2011 Published by Elsevier Inc. doi:10.1016/j.niox.2011.12.005 ⇑ Corresponding author at: Institute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Alkotas u. 44, TF, Budapest, Hungary. Fax: +36 1 356 6337. E-mail addresses: radak@mail.hupe.hu, radak@tf.hu (Z. Radak). Nitric Oxide 26 (2012) 89–94 Contents lists available at SciVerse ScienceDirect Nitric Oxide journal homepage: www.elsevier.com/locate/yniox