| Postherpetic neuralgia (PHN) is sequela of acute herpes zoster. The skin damage has recovered, but violent pain remains as an altauna to aged patients, who are subject to pain for long-term, with depression and tendency of committing suicide. At present there are some comprehensive treatment modalities such as medication, microwave, laser, ultraviolet and psychotherapy, etc, which are used to relieve symptoms by the analgesic effects, however, the curative effects are not satisfactory. A focused ultrasound beam can be introduced accurately into the target in depth to cause localized temperature rise, which has characteristics including improving the micro circulation and etc. Focused ultrasound treatment may be a promising modality for curing PHN in future; hence we have carried out a preliminary study on clinical application of focused ultrasound treatment of PHN. Part 1 Observation on the biological effects caused by focused ultrasound in bovine liver samples in vitroObjective: The purpose of this study was to observe the length, width, shape and distance to the surface of the focal region during focused ultrasound fixed-point exposure and to summary the regular pattern, then to screen the safety dose for using in animal experiment during focused ultrasound linear scanning .Methods:(1) A prototype device provided by Chongqing Haifu Technology Co, Ltd. was used to fixed-point irradiate the in vitro bovine liver samples with various time duration 1s, 2s, and 3s, and different sound powers 4.5W and 5W under the same frequency of 10.06MHz, by the mode of continuous single exposure. After irradiation, the length, width, distance to the surface and the morphological changes of the focal region were observed. (2) Under different sound powers of 3W, 3.5W, 4W, 4.5W and 5W, a linear scanning was used to irradiate the bovine liver samples at a velocity 2~4mm/s. The distance to surface and morphological changes of the focal regions were observed. Appropriate parameters were screened for animal experiments. Results: Under the same conditions the distance to the skin, length ,width and the changes of morphology of biological focal region were the same. The distance to skin was 5mm. Higher power was used, severer damage and larger dimension of the BFR were led to. Under the same power and frequency, longer exposure duration were used, severer damage and larger dimension of the BFR were caused by focused ultrasound fixed-point exposure. Under the sound power of 3W, at the linear scanning velocity of 2~4mm/s, no coagulative necrosis was noticed by gross observation. Conclusion: The prototype device is of good controllability with stable function. With the velocity of 2~4mm/s under less than 3W, the ultrasound exposure could be a safe dose for skin treatment.Part 2 The biological effects study of focused ultrasound exposure on the skin of Miniswine1. A dose study on the skin of Miniswine after focused ultrasound exposureObjective: The aim of this study was to observe the biological effects and screen safety dose after focused ultrasound exposure on the skin of Miniswine with various parameters. Methods: Under different sound powers of 3W, 2.5W, 2W, 1.5W, 1W, and 0.5W, back skin of five Miniswine were irradiated at a velocity of 2~4mm/s. The morphological changes and recovery time after exposure were observed. Samples of the exposed skin were obtained for microscopic examination. Results: With irradiation sound powers of 3W, 2.5W, 2W, 1.5W, 1W, and 0.5W at the velocity of 2~4 mm/s, congestion of the exposed skin was found. No evident coagulative necrosis was noticed under the microscopic examination. Conclusion: It could be a safe dose for clinical application.2. A study on pathologic changes of the skin of Miniswine after focused ultrasound exposureObjective:The aim of this study was to explore the pathologic changes of the skin of Miniswine after focused ultrasound irradiation, and to initially explore the possibility of treating postherpetic neuralgia by using focused ultrasound. Methods: Under the sound power of 2W and frequency of 10.06MHz, at the velocity of 2~4mm/s the prototype device was used to irradiate the back skin of eight Miniswine by the mode of continuous linear scanning. Samples of the irradiated skin immediately, the third day, seventh day and fourteenth day after exposure were taken for light and electroscopic examination, and the results were self controlled. Results: There were congestion and edema found at irradiated area instantly after focused ultrasound exposure, the skin was slightly rigid but intact with some temperature rise. At the third after exposure, the congestion and edema was alleviated, while the treated area remained rigid ,the temperature turns normal. At the seventh day after irradiation, the treated skin showed slight edema, while at the fourteenth day, the skin recovered normal. Microscopic changes: Evident congestion and edema were found in dermal layer instantly after irradiation. Angiotelectasis and chronic inflammatory cell infiltration were found at the third day. There were vascular proliferation and inflammatory cell infiltration at the seventh day. The skin recovered completely at the fourteenth day. Electron microscopic changes: Instantly, the third day and the seventh day after ultrasound irradiation, mitochondria swelling and micropinocytotic vesicle increase, mitochondria of mechanocyte swelling and rough endoplasmic reticulum dilatation in fibroblast and nerve fibers swelling were found. At the fourteenth day, all recovered normal. Conclusion: The results indicated that focused ultrasound is able to produce reversible damage to the dermis of the skin, to improve minicirculation, and to promote hyperplasia and repair of fibroblast and nerve endings at the velocity of 2~4mm/s under the sound power of 2W .3. Histopathological changes of the Miniswines'skin exposed repeatedly to focused ultrasoundObjective: The aim of this study was to explore the histopathological changes of the Miniswines'skin exposed repeatedly to focused ultrasound, and to provide experimental basis for the safety and effectiveness of clinical treatment of postherpetic neuralgia (PHN) by repeated focused ultrasound exposure. Methods: The six animals'skin were irradiated by a linear scanning mode at the velocity of 2~4mm/s under the sound power of 2W and frequency of 10.06MHz once every day for three days . The skin changes were observed and evaluated under light and electron microscopes. Results: Evident congestion and edema were found at the irradiated area by gross observation instantly after focused ultrasound exposure. Under light microscope there were congestion and edema, angiotelectasis and inflammatory cell infiltration in epidermis. No coagulative necrosis was noted. Under electron microscope, instantly after ultrasound irradiation, mitochondria swelling of endothelial cell of blood vessel, micropinocytotic vesicles increase, mitochondria swelling of fibroblasts, rough endoplasmic reticulum dilatation and mitochondfia swelling of nerve fibers were noted. Conclusion: (1)Reversible damage at epidermis could be induced by the research dose of focused ultrasound at the velocity of 2~4mm/s under the sound power of 2W. (2)The animals'skin were not damaged by repeatable ultrasound irradiation of specific dose and time . It is effective and safe to treat postherpetic neuralgia by repeatable ultrasound irradiation.Part 3 A clinical preliminary study of focused ultrasound treatment of postherpetic neuralgiaObjective: The purpose of this study was to explore the feasibility and effective of using focused ultrasound to treat postherpetic neuralgia. Methods: A total of forty patients with PHN were treated by focused ultrasound and microwave, respectively. Twenty in ultrasound group were treated through contacting treatment by successive linear scanning, at the velocity of 6~8mm/s , under the sound power of 2W, once a day for three days. And then the effects were assessed and compared with that of the microwave group. Results: The short-term effect of the ultrasound group was better than that of microwave group, throughχ2 test, we found there was significant difference between the two groups (p<0.05). The difference between the long-term results of two groups were not significant (P>0.05). Two to three days after treatment by both modalities, part of the patients found pain but which was evidently alleviated comparing to before treatment. Conclusion: Focused ultrasound was effective and feasible to treat PHN. However, the long-term effectiveness was not evidently better than other modalities. Further study about biological effects and treatment plan is necessary in the purpose of enhancing the long-term effectiveness of focused ultrasound.
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