Razi Journal of Medical Sciences

fa اثر ضددردی سیمواستاتین پس از بستن عصب سیاتیک Analgesic Effect of Simvastatin after Sciatic Nerve Ligation دامپزشکی veterinarian پژوهشي Research <div style="text-align: justify;">زمینه و هدف: هدف اصلی این پژوهش، مطالعهی اثر سیمواستاتین روی تحمل درد و ارزیابی آنتاگونیست ها به دنبال آسیب عصب سیاتیک در موش صحرایی بود. روش کار: این تحقیق طی 2 مرحله آزمایشی بر روی 85 موش صحرایی نر بالغ و محدودهی وزنی 180-200 گرم، استفاده شد. تمامی حیوانات قبل از جراحی از نظر سلامت حرکتی ارزیابی شده و سپس تمامی موشها با تزریق داخل صفاقی داروهای کتامین هیدروکلراید (mg/kg60) و زایلازین (mg/kg10) بیهوش شدند و پس از اسکراب و آماده سازی اولیه پای راست حیوانات، آنها را به پهلوی چپ حالت گماری کرده و برشی در پوست خلفی-خارجی ناحیه رانی پای چپ داده شد. عضلات و فاسیا را به آرامی کنار زده و پس از در معرض دید قرار گرفتن عصب سیاتیک، با استفاده از هموستات ریز عصب سیاتیک تحت فشار به مدت 60 ثانیه قرار گرفت. به منظور ردیابی، محل آسیب را با بخیه زدن نزدیکترین عضله به محل لهشدگی با استفاده از نخ بخیه (0-5) سیلک غیرقابلجذب نشانهگذاری کرده و سپس عضلات را کنار هم گذاشته و بافت زیرجلد و پوست به ترتیب با استفاده از نخ ویکریل(0-4) و نایلون ( 0- 3) به روش ساده سرتاسری و تکیساده بخیه شد. در آزمون فرمالین، سیمواستاتین، ( mg/kg2، 4 و 8) یا مورفین (mg/kg5) به موش‌ها تزریق شد. در موش‌ها تزریق همزمان سیمواستاتین ( mg/kg8) + نالوکسان (mg/kg2) یا سپروهپتادین (mg/kg 4)، سایمیتیدین (mg/kg12.5)، انجام شد. سپس تست فرمالین صورت گرفت و زمان لیسیدن اندازهگیری شد. حیوانات به 4 گروه تقسیم شدند: گروه 1: آسیب عصبی بدون درمان، گروه 2و3 و4 گروههای درمان با سیمواستاتین بود. موشهای گروه 2 (با دوز  mgkg 2) و گروه 3 (با دوزmgkg 4) و گروه 4 (با دوزmgkg 8) تحت درمان با سیواستاتین قرار گرفتند. در هر گروه 5 سر موش قرار گرفت که در دو بازهی زمانی 2 و 4 هفته مورد ارزیابی قرار گرفتند. تحلیل آماری داده‌‌های حاصله با استفاده از نرم‌افزار IBM SPSS Statistics 26  (SPSS25)، انجام شد. یافته‌ها: یافته‌های توصیفی متغیرهای موردمطالعه، شامل شاخص‌هایی از قبیل میانگین، انحراف معیار، خطای استاندارد و ... محاسبه و گزارش گردید. نتیجه‌گیری: براساس نتایج به دست آمده به نظر میرسد که سیمواستاتین با دز mg/kg 8 در کاهش زمان عکسالعمل درد در گروه تحت درمان تاثیر دارد.</div> <div style="text-align: justify;">Background & Aims: Pain is divided into two main types, fast and slow. Pain receptors are composed of free nerve endings and use two separate pathways to transmit pain signals to the CNS. Sharp pain signals are produced by mechanical and thermal pain stimuli. These signals are transmitted to the spinal cord by peripheral nerves through Aδ fibers at a speed of 3-15 m/s. On the contrary, slow and chronic pain signals are mainly produced by chemical pain stimuli, but sometimes stable mechanical or thermal stimuli can also produce these signals. These signals are transmitted to the spinal cord by C-type fibers at a speed of 0.5 to 2 m/s (1). The mechanisms of neuropathic pain are not fully known, but the mechanisms proposed in the pathogenesis of this pain include the role of glial cells as supporting cells of the central nervous system, changes in sodium and potassium voltage-dependent channels, afferents adjacent to the neuron. It is damaged. Different neural pathways are affected differently. Therefore, identification of these pathways is important in determining the analgesic and medicinal mechanisms from physiological aspects. Although there are many studies in this field, one of the existing problems is the rate of recovery and return of nerve activity after injury. The results of researchers' research have brought relatively acceptable results, which were not without problems. In the present research, due to the high incidence of peripheral nerve injuries caused by blows and fractures in humans and animals, efforts will be made to find a drug or drug combination to accelerate the healing process of damaged nerves following experimental sciatic nerve injury in the rat animal model. Therefore, the present study will be conducted in order to investigate the analgesic effects of simvastatin and its neurophysiological interaction with the involved systems following experimental sciatic nerve ligation in rats. Methods: This research was used in 2 experimental phases on 85 adult male rats weighing 180-200 grams. These animals were transferred to the laboratory animal breeding and maintenance center of the veterinary school and were kept in standard mouse cages under standard conditions. All animals were evaluated for motor health before surgery, and then all mice were anesthetized by intraperitoneal injection of ketamine hydrochloride (60 mg/kg) and xylazine (10 mg/kg), and after scrubbing and initial leg preparation The animals were placed on their left side and an incision was made in the posterior-external skin of the thigh area of the left leg. The muscles and fascia were gently removed and after exposing the sciatic nerve, the sciatic nerve was compressed for 60 seconds using a micro hemostat. In order to trace, the injury site is marked by suturing the muscle closest to the crush site using non-absorbable silk suture (0-5) and then the muscles are placed together and the subcutaneous tissue and skin are The sequence was stitched using vicryl thread (0-4) and nylon (0-3) in a simple all round and single stitch method. Then formalin test was done and licking time was measured. The animals were divided into 4 groups: group 1: nerve damage without treatment, group 2, 3 and 4 were treated with simvastatin. Mice in group 2 (with a dose of 2 mg/kg), group 3 (with a dose of 4 mg/kg) and group 4 (with a dose of 8 mg/kg) were treated with Sivastatin. There were 5 mice in each group and they were evaluated in two time intervals of 2 and 4 weeks. Results: As seen in Figure 1, the injection of morphine (5 mg/kg) significantly reduced the pain time caused by the formalin test compared to the control group (P<0.05). The level of 4 and 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). According to the results of the statistical analysis of repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to naloxone during the acute and chronic phases is presented in Figure 2. Naloxone injection (2 mg/kg) had no effect on pain time caused by formalin test compared to the control group (P>0.05). The level of 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). The combined injection of naloxone plus simvastatin significantly reduced the analgesic effects of simvastatin compared to the simvastatin alone group (P<0.05). According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to speroheptadine during the acute and chronic phases is presented in Figure 3. According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to cimetidine during the acute and chronic phases is presented in graph No. 4 . Conclusion: The aim of this study is the analgesic effects of simvastatin following experimental sciatic nerve ligation in rats. According to the obtained results, it was determined that the analgesic effects of simvastatin are dose-dependent and the findings of this test show that the effective dose (8 mg/kg) of simvastatin alone has been able to create a significant effect in reducing the painful effects of formalin in animals. It has also caused a significant decrease in the response time to formalin pain stimulus in animals. Antagonists naloxone, cyproheptadine and cimetidine were able to inhibit the analgesic effects in acute and chronic phase. Simvastatin activates the PI3K/AKt pathway and increases neurogenesis through BDNF and (Vascular endothelial growth factor) (12). Simvastatin increases the phosphorylation and expression of BDNF and VEGF gene in (Dentate gyrus) DG. As a result, cell proliferation increases and differentiation occurs in the DG area and brain recovery increases (14). Therefore, simvastatin may cause gene expression of growth factors, production of protein kinases, and subsequent induction of neurogenesis in the DG of the hippocampus, increasing dendritic branches through the activation of AKt through the signaling pathway (15). The effects of simvastatin on ischemia-reperfusion injury of the sciatic nerve in adult rats, as a result, administration of simvastatin before ischemia shows protective properties in nerve re-injury and improves blood supply again (16).</div> سیمواستاتین, کاهش زمان تحمل درد, موش صحرایی Simvastatin, Reduction of Pain Tolerance Time, Rats 106 115 http://rjms.iums.ac.ir/browse.php?a_code=A-10-6958-2&slc_lang=fa&sid=1 Mahtab Mohammadzadeh مهتاب محمدزاده 3900319475328460090833 3900319475328460090833 No DVM student, Department of Veterinary Medicine, Science and Research Unit, Islamic Azad University, Tehran, Iran دانشجوی دکتری، گروه دامپزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران Ahmad Asghari احمد اصغری dr.ahmad.asghari@gmail.com 3900319475328460090834 3900319475328460090834 Yes Associate Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran دانشیار، گروه علوم درمانگاهی، دانشکده دامپزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران Shahin Hassanpour شاهین حسن پور 3900319475328460090835 3900319475328460090835 No Assistant Professor, Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran استادیار، گروه علوم پایه، بخش فیزیولوژی، دانشکده دامپزشکی، واحد علوم تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران