ORIGINAL ARTICLE Preventive and curative effects of radon inhalation on chronic constriction injury-induced neuropathic pain in mice K. Yamato, T. Kataoka, Y. Nishiyama, T. Taguchi, K. Yamaoka Graduate School of Health Sciences, Okayama University, Japan Correspondence Kiyonori Yamaoka E-mail: yamaoka@md.okayama-u.ac.jp Funding sources None. Conflicts of interest None declared. Accepted for publication 17 July 2012 doi:10.1002/j.1532-2149.2012.00210.x Abstract Background: Radon therapy is clinically useful for the treatment of pain-related diseases. However, there have been no studies regarding the effects of radon inhalation on neuropathic pain. In this study, we aimed to determine whether radon inhalation actually induced a remission of neuropathic pain and improved the quality of life. Methods: First, we investigated the antinociceptive effects of radon inhalation in the chronic constriction injury (CCI) model of neuropathic pain. We evaluated pain behaviour in mice before and after CCI surgery, using von Frey test. Pretreated mice received CCI surgery immediately after 24-h inhalation of radon at background (BG) concentration (c. 19 Bq/m 3 ), or at a concentration of 1000 or 2000 Bq/m 3 , and post-treated mice inhaled similar levels of radon 2 days after CCI surgery. Results: CCI surgery induced mechanical allodynia and hyperalgesia on a plantar surface of mice, as assessed using von Frey test, and 2000 Bq/m 3 radon inhalation alleviated hyperalgesic conditions 22–37% compared to BG level concentration. Concurrently, CCI surgery increased norepineph- rine (NE), tumour necrosis factor-alpha (TNF-a) and nitric oxide (NO) concentrations in plasma, and leukocyte migration in paws. Furthermore, CCI-induced neuropathy reduced superoxide dismutase (SOD) activity. Treatment with radon inhalation, specifically at a concentration of 2000 Bq/m 3 , produced antinociceptive effects, i.e., lowered plasma TNF-a, NE and NO levels and restored SOD activity, as well as pain-related behaviour. Conclusions: This study showed that inhalation of 2000 Bq/m 3 radon prevented and alleviated CCI-induced neuropathic pain in mice. 1. Introduction Neuropathic pain is a major pain-related disease and a chronic condition induced by many factors such as central/peripheral nerve injury or metabolic distur- bances (diabetes) (Dworkin et al., 2003; Berrocoso et al., 2011). The prevalence of chronic pain is 10–40% of the general population (Neville et al., 2008; Sun et al., 2012). Neuropathic pain is characterized by hyperalgesia (an increased response to noxious stimuli) and allodynia (a pain response to normally innocuous stimuli; Bridges et al., 2001; Iwata et al., 2011). Many factors and mechanisms are involved in hyperalgesia and allodynia following nerve injury (Devor et al., 1994) such as novel ectopic sensitivity along injured nerves, changes in sensitization to and expression of norepinephrine (NE; Sato and Perl, 1991) and epineph- rine (Khasar et al., 1999; Chen and Levine, 2005). Numerous studies suggested that nerve injury-induced inflammatory responses play an important role in neu- ropathic pain (Kiguchi et al., 2010; Sun et al., 2012). Tumour necrosis factor-alpha (TNF-a), for example, is a major proinflammatory cytokine whose levels are increased under pathological conditions (Marchand et al., 2005; Zhang et al., 2011) such as in neuropathic pain (Schäfers et al., 2003; Xu et al., 2006). The pro- 480 Eur J Pain 17 (2013) 480–492 © 2012 European Federation of International Association for the Study of Pain Chapters