Alexander A. Radzievsky

Suppression of pain sensation caused by millimeter waves: a double-blinded, cross-over, prospective human volunteer study.

UNLABELLED We conducted a double-blinded, randomized, cross-over, prospective trial to evaluate the pain relief effect of millimeter waves (MW) under experimental conditions. The cold pressor test was used as a model of tonic aching pain. Twelve healthy male volunteers were exposed to an active medical MW generator and to a disabled sham generator with at least 24 h between exposures. Characteristics of continuous-wave electromagnetic output from the active generator were: wavelength 7.1 mm, incident power density 25 +/- 5 mW/cm2, and duration of exposure 30 min. MW produced a significant (P < 0.05) suppression of pain sensation, with an average 37.7% gain in pain tolerance and a 49.3% increase in pain sensitivity range (the latter being the difference between pain tolerance and pain threshold values). Of the 12 volunteers, 7 (58.3%) reacted to the active MW generator with an increased pain tolerance, and the individual reactions varied from 120% to 315% comparison with their own preexposure levels. MW therapy can potentially be used as a supplementary or alternative treatment for pain relief. IMPLICATIONS Pain management is still a significant medical problem. In a double-blinded, experimental setting, we confirmed that low-intensity millimeter wave therapy can reduce pain sensitivity in healthy human volunteers and can potentially be used as a supplementary or alternative treatment for pain relief.

Hypoalgesic effect of millimeter waves in mice: Dependence on the site of exposure

Based on a hypothesis of neural system involvement in the initial absorption and further processing of the millimeter electromagnetic waves (MW) signal, we reproduced, quantitatively assessed and compared the analgesic effect of a single MW treatment, exposing areas of skin possessing different innervation densities. The cold water tail flick test (cTFT) was used to assess experimental pain in mice. Three areas of exposure were used: the nose, the glabrous skin of the right footpad, and the hairy skin of the mid back at the level of T5-T10. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15mW/cm2; and duration = 15 min. The maximum hypoalgesic effect was achieved by exposing to MW the more densely innervated skin areas--the nose and the footpad. The hypoalgesic effect in the cTFT after MW exposure to the murine back, which is less densely innervated, was not statistically significant. These results support the hypothesis of neural system involvement in the systemic response to MW.

Peripheral neural system involvement in hypoalgesic effect of electromagnetic millimeter waves.

In a series of blind experiments, using the cold water tail-flick test (cTFT) as a quantitative indicator of pain, the hypoalgesic effect of a single exposure of mice to low power electromagnetic millimeter waves (MW) was studied. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm2; and duration = 15 min. MW treatment was applied to the glabrous skin of the footpad. Exposure of an intact murine paw to the MW resulted in a statistically significant hypoalgesia as measured in the cTFT. These mice were able to resist cold noxious stimulation in the cTFF more than two times longer than animals from the sham-exposed group. A unilateral sciatic nerve transection was used to deafferent the area of exposure in animals from one of the experimental groups. This surgery, conducted six days before the MW treatment, completely abolished the hypoalgesic effect of the exposure to MW. The results obtained support the conclusion that the MW-skin nerve endings interaction is the essential step in the initiation of biological effects caused by MW. Based on our past and present results we recommend that in order to obtain a maximum therapeutic effect, densely innervated skin areas (head, hands) need to be used preferentially for exposure to MW in clinical practice.

Antipruritic effect of millimeter waves in mice: Evidence for opioid involvement

In our previous studies, exposure of mice to millimeter waves (MW) increased the duration of anesthesia caused by either ketamine or chloral hydrate, and this effect was blocked by naloxone. To further characterize the biological effects of MW, we have chosen a new animal model of experimental itch. Male Swiss albino mice were injected s.c. in the rostral part of the back with the pruritogenic agent, compound 48/80, with or without naloxone pretreatment. After a 15-min exposure of mice to MW (frequency, 61.22 GHz; incident power density, 15 mW/cm2), the number of scratches of the injected site was counted for 90 min post-injection. MW inhibited the scratching activity of mice by more than 2 times in comparison with the sham-exposed controls (p<0.005). Pretreatment of animals with (-)-naloxone (0.1-1.0 mg/kg, i.p.) suppressed the antipruritic effect of MW in a dose-dependent manner, while the inactive enantiomer (+)-naloxone at 1 mg/kg did not alter the effect. These results suggest that MW trigger the release of opioids in exposed subjects.

Millimeter wave effects on electrical responses of the sural nerve in vivo

Millimeter wave (MMW, 42.25 GHz)-induced changes in electrical activity of the murine sural nerve were studied in vivo using external electrode recordings. MMW were applied to the receptive field of the sural nerve in the hind paw. We found two types of responses of the sural nerve to MMW exposure. First, MMW exposure at the incident power density >/=45 mW/cm(2) inhibited the spontaneous electrical activity. Exposure with lower intensities (10-30 mW/cm(2)) produced no detectable changes in the firing rate. Second, the nerve responded to the cessation of MMW exposure with a transient increase in the firing rate. The effect lasted 20-40 s. The threshold intensity for this effect was 160 mW/cm(2). Radiant heat exposure reproduced only the inhibitory effect of MMW but not the transient excitatory response. Depletion of mast cells by compound 48/80 eliminated the transient response of the nerve. It was suggested that the cold sensitive fibers were responsible for the inhibitory effect of MMW and radiant heat exposures. However, the receptors and mechanisms involved in inducing the transient response to MMW exposure are not clear. The hypothesis of mast cell involvement was discussed.

Millimeter-wave-induced hypoalgesia in mice: dependence on type of experimental pain

Millimeter-wave therapy (MWT) is based on the systemic biological effects resulting from local exposure of skin to low-power electromagnetic waves of millimeter wavelength. The aims of the present study are to quantitatively evaluate hypoalgesic effects of MWT in murine experimental models of acute and chronic neuropathic pain, and to compare them with the previously determined MWT-induced hypoalgesia in an experimental model of chronic nonneuropathic pain, and also to assess the ability of local heating with a Holmium YAG laser to produce hypoalgesia in mice. The cold and hot water tail-flick tests and the unilateral chronic constriction injury (CCI) to the sciatic nerve were used as pain models. The MWT characteristics were: frequency =61.22 GHz; average power density =13.3 mW/cm/sup 2/; duration of exposure =15 min; and area of exposure-nose. This study demonstrated that a single MWT most effectively suppressed chronic nonneuropathic pain. Less effectively, a single MWT reduced pain sensitivity in the murine model of acute pain, and was ineffective in the model of chronic neuropathic pain. However, multiple MWT reduced the symptoms that developed following CCI. The local heating of the exposed area did not produce hypoalgesia. The findings support the use of MWT in chronic pain states.

Destruction of cutaneous melanoma with millimeter wave hyperthermia in mice

Millimeter wave irradiation has been found to generate a dose-dependent heating of skin, providing an opportunity for destruction of heat-sensitive cutaneous tumors including melanomas. In vitro irradiation of epidermal keratinocytes and melanoma cells revealed distinct susceptibility of melanoma cells to MMW hyperthermia with higher thermotolerance of keratinocytes. No significant species differences were found when human and murine keratinocytes and melanoma cells were compared. In vivo irradiation of cutaneous melanoma in mice with MMW at the incident power density of 1.25 W/cm/sup 2/ for 30 min resulted in a selective melanoma destruction. Histological analysis showed no tissue damage of normal skin cells (necrosis or apoptosis) within the exposed skin areas. We hypothesize that MMW irradiation would be a useful treatment modality for cutaneous melanoma in humans.

Single millimeter wave treatment does not impair gastrointestinal transit in mice

Millimeter wave treatment (MWT) is based on those biological effects that develop following skin exposure to low power electromagnetic waves. This method of treatment is in wide clinical use in several Eastern European countries for treatment of a variety of conditions, including pain syndromes. However, most treatment modes of MWT were developed empirically, and certain indications and contraindications for the use of MWT remain to be established. In our previous blind experiments we have shown that the hypoalgesic effect of MWT may be quantitatively evaluated, and most probably mediated by the neural system in general, and the system of endogenous opioids in particular. Taking in consideration a well-known ability of opioids to cause gastrointestinal disturbances, which could limit clinical application of MWT, the main aim of the present study was to investigate whether a single MWT, that can produce opioid-related hypoalgesia, may also retard gut transit and colorectal passage in mice. The charcoal meal test was used to quantitatively evaluate upper gastrointestinal transit, and the glass bead test was employed to examine colonic propulsion in mice. MWT was applied to the nose area of mice. The MWT characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm(2); and duration = 15 min. The results obtained have shown that MWT does not significantly change small intestinal or colonic transit in mice, and thus suppression of gastrointestinal motility should not be a setback in the clinical use of MWT.