Mikhail A. Rojavin

Morphine treatment in vitro or in vivo decreases phagocytic functions of murine macrophages

Studies were performed to compare in vitro and in vivo effects of morphine on the phagocytic function of murine peritoneal macrophages. Macrophage monolayers were incubated with Candida albicans for 30 min in the absence of autologous serum. Morphine added in vitro was found to decrease both the phagocytic activity (percent of phagocytic cells) and the phagocytic index (average number of ingested yeasts per cell) in a concentration-dependent manner, with maximal effects of 26% and 41%, respectively, at 10(-6) M. When morphine was administered in vivo via an implanted 75-mg pellet, there was a 22% decrease in phagocytic activity and a 40% decrease in the phagocytic index. Naltrexone completely blocked the effects of morphine both in vitro and in vivo. The results suggest that morphine is capable of interacting directly with opioid receptors on macrophages, resulting in a decrease in phagocytic function.

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.

In Vivo Effects of Millimeter Waves on Cellular Immunity of Cyclophosphamide-Treated Mice

Reactions of peritoneal macrophages (PM) and T lymphocytes of BALB/c mice to in vivo exposure to millimeter (MM) waves were studied. The mice were additionally treated with the antineoplastic drug cyclophosphamide (CPA) 100 mg/kg. Phagocytosis of Candida albicans cells by PM obtained from mice treated with CPA and MM waves, alone and in combination, was studied in vitro using a monolayer technique. Proliferation of murine T cells (splenocytes) was studied by 3H-thymidine incorporation into DNA of T lymphocytes without stimulation and after stimulation with anti-CD3 antibody 2C11. The results of this study show that 61.22 GHz MM waves with an incident power density of 15 mW/cm2 and a peak SAR of 420 W/kg significantly reduce the toxic effects of CPA on cellular immunity of mice in vivo as observed by the increased PM phagocytic activity and enhancement of T-cell proliferation.

Interaction of Cyclophosphamide and Ketamine in vivo

Cyclophosphamide 100 mg/kg i.p. increased the duration of ketamine-induced anesthesia in BALB/c mice by 39%. However, combined action of these two substances did not change the number of splenocytes, proliferation of T cells, or phagocytic activity of murine peritoneal macrophages against Candida albicans.