int. j. radiat. biol 2000, vol. 76, no. 4, 575 ± 579 Pain relief caused by millimeter waves in mice: results of cold water tail ick tests M. A. ROJAVIN, A. A. RADZIEVSKY*, A. COWAN† and M. C. ZISKIN (Received 7 April 1999; accepted 4 June 1999) Abstract. study, naloxone exhibited its inhibitory activity in Purpose : To nd out if millimeter waves can decrease experimental a dose-dependent manner and stereoselectively pain response in mice using cold water tail ick test. ( Õ )-naloxone exerted the eÚect, while the biologic- Materials and methods : Male Swiss albino mice (15 mice per group) ally inactive enantiomer ( +)-naloxone did not. were exposed to continuous millimeter waves at a frequency of Any new method of pain relief is clinically import- 61.22 GHz with incident power densities (IPD) ranging from 0.15 to 5.0 mW/cm 2 for 15min or sham exposed. Latency of ant, especially a non-pharmacological non-invasive tail withdrawal in a cold water (1 Ô 0.5ßC) tail ick test was procedure such as mm waves. To verify some of the measured before the exposure (baseline) and then four times clinical reports, published mostly in the Russian after the exposure with 15min breaks. language (Lyan and Votoropin 1996, Shliapak et al. Results : The mean latency of the tail ick response in mice 1996, Vinogradov et al. 1993), Lyan and Votoropin exposed to millimeter waves was more than twice that of sham- exposed controls ( p < 0.05). This eÚect was proportional to the 1996, Shliapak et al. 1996, Bakalyuk 1997), a double- power of millimeter waves and completely disappeared at an blind phase I pilot clinical trial was conducted with IPD level of < 0.5 mW/cm 2 . Pretreatment of mice with the healthy human volunteers, and it was found that mm opioid antagonist naloxone (1mg/kg i.p.) blocked the eÚect of waves suppressed experimental pain (cold pressor millimeter waves. test) in human subjects (Radzievsky et al. 1999). Conclusions : Results suggest that the antinociceptive eÚect of millimeter waves is mediated through endogenous opioids. Based on the above ndings, the present authors have formulated the hypothesis that mm waves trig- ger the release of endogenous opioids, and this results 1. Introduction in decreased pain sensitivity in humans and animals. In the present work, the mouse cold water tail ick Electromagnetic millimeter waves (mm waves) with low ( < 20mW) output power have been used for assay was chosen to test this hypothesis. medical purposes for the last 15 years, with sedation and pain relief being the most frequent therapeutic 2. Materials and methods eÚects registered in the majority of patients 2.1. Animals (Pakhomov et al. 1998, Rojavin and Ziskin 1998). Pain relief is usually reported by patients with various Male Swiss albino mice (22–25 g; Ace diseases after the rst two to three sessions of mm Laboratories, Doylestown, PA) were used. The wave exposure, which suggests that a certain non- animals were acclimated for 3–4 days to a 12/12h specic mechanism of pain relief is triggered by this light/dark cycle at an ambient temperature of method of treatment. 21 Ô 1ß C with an appropriate diet and drinking water No laboratory experiments aimed at studying the ad libitum. The Institutional Animal Care and Use above eÚects are known of, but several related obser- Committee approved the protocol of this experiment. vations have been made in animals: mm waves increase the duration of ketamine or chloral hydrate 2.2. Reagents anaesthesia (Rojavin and Ziskin 1997) and decrease experimental itch (Rojavin et al. 1998). In both cases, Naloxone hydrochloride was obtained from Astra the eÚects of mm waves were blocked by the opioid Pharmaceutical (Westborough, MA, USA). antagonist naloxone indicating that endogenous opioids were probably involved. In the latter 2.3. Experimental set-up *Author for correspondence. The characteristics of the exposure chamber and e-mail: aradziev@unix.temple.edu experimental set-up have been previously described Richard J. Fox Center for Biomedical Physics and (Rojavin and Ziskin 1997). Briey, the exposure, †Department of Pharmacology, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA. sham exposure and testing of mice were conducted International Journal of Radiation Biology ISSN 0955-3002 print/ISSN 1362-3095 online © 2000 Taylor & Francis Ltd http://www.tandf.co.uk/journals/tf/09553002.html