The Effect of Bone Mesenchymal Stem Cell Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review with Meta-Analysis

Stem cell transplantation has been considered a possible therapeutic method for neuropathic pain. However, no quantitative data synthesis of stem cell therapy for neuropathic pain exists. Therefore, the present systematic review and meta-analysis assessed the efficacy of bone marrow mesenchymal stem cell (BMMSC) transplantation on alleviating pain symptoms in animal models of neuropathic pain. In the present meta-analysis, controlled animal studies assessing the effect of administrating BMMSC on neuropathic pain were included through an extensive literature search of online databases. After collecting data, effect sizes were computed and the standardized mean difference (SMD) with 95% confidence interval (CI) was entered in all analyses. Random-effects models were used for data analysis. Sensitivity and subgroup analyses were performed to investigate expected or measured heterogeneity. Finally, 14 study were included. The analyses showed that BMMSC transplantation lead to significant improvement on allodynia (SMD = 2.06; 95% CI, 1.09 to 3.03; I(2) = 99.7%; P < .001). The type of neuropathy (P = .036), time between injury and intervention (P = .02), and the number of transplanted cells (P = .023) influence the improvement of allodynia after BMMSC transplantation. BMMSC transplantation has no effect on hyperalgesia (SMD = .3; 95% CI, -1.09 to 1.68; I(2) = 100%; P < .001) unless it occurs during the first 4 days after injury (P = .02). The present systematic review with meta-analysis suggests that BMMSC transplantation improves allodynia but does not have any significant effect on hyperalgesia unless it is given during the first 4 days after injury

Nanocurcumin as a radioprotective agent against radiation-induced mortality in mice

Objective(s): Curcumin, a natural plant product, is commonly known as wonder drug of life, but the poor bioavailability of its free form has hindered its clinical development. The aim of the present study was to investigate the radioprotective effect of nanocurcumin on survival of mice under whole body X-ray irradiation. Materials and Methods: The Naval Medical Research Institute (NMRI) mice randomly assigned to separate groups and received nanocurcumin via oral gavage at different time points related to irradiation. The survival of mice was evaluated daily for 30 days post-irradiation and finally, the LD50/30 was calculated using Probit analysis. The 30-day survival curve was plotted using the Kaplan-Meier survival curve and the median survival of different subgroups was compared using log-rank test. The P-values less than 0.05 were considered significant. Results: Our results showed that the administration of oral nanocurcumin could effectively reduce the mortality rate in the irradiated mice. Five days pretreatment with nanocurcumin (4 mg/kg/day) induced maximum radioprotective effect. The LD50/30 was 7.18 Gray (Gy) (95% confidence interval [CI]: 6.59-7.77) and 8.78 Gy (95% CI: 8.14-9.50) for irradiation-only and the optimum nanocurcumin group (pre-irradiation group), respectively (dose reduction factor [DRF] = 1.22). Continued administration of nanocurcumin up to seven days post-irradiation resulted in no further radioprotection. Conclusions: The results obtained in this study confirmed the efficacy of nanocurcumin as a radioprotective agent against radiation-induced mortality in mice. The specific characteristics of nanocurcumin, such as non-toxicity, edibility, availability, make this phytochemical as a potential radioprotective agent in the radiotherapy setting and radiation accidents. Further clinical studies are highly recommended

The Effect of Intrathecal Administration of Muscimol on Modulation of Neuropathic Pain Symptoms Resulting from Spinal Cord Injury; an Experimental Study

Introduction: Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA) have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAA receptor agonist in spinal cord injury (SCI) model of neuropathic pain. Methods: In the present experimental study male Wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t.) three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. Results: Muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p&lt;0.001), mechanical hyperalgesia (df: 24, 5; F= 7.8; p&lt;0.001), cold allodynia (df: 24, 5; F= 6.96; p&lt;0.001), and mechanical allodynia (df: 24, 5; F= 15.7; p&lt;0.001). The effect of doses of 0.1 µg and 1 µg were also significant. In addition, the efficacy of different doses of muscimol didn't have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24), mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75), cold allodynia (df: 24, 5; F= 0.8; p= -0.56), and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86). Conclusion: The finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. Also the effect of GABAA agonist is short term and its effectiveness gradually decreases by time

The efficacy of Schwann cell transplantation on motor function recovery after spinal cord injuries in animal models: A systematic review and meta-analysis

Aim: This article aimed to assess the efficacy of Schwann cell transplantation on motor function recovery in animal model of spinal cord injuries via meta-analysis. Methods: An extended search was carried out in the electronic databases of Medline (via PubMed), EMBASE (via OvidSP), CENTRAL, SCOPUS, Web of Science (BIOSIS), and ProQuest. Finally, 41 eligible studies conducted on 1046 animals including 517 control animals and 529 transplanted animals were included in the meta-analysis. Pooled standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (95% CI) were reported. Results: The findings showed that treatment with Schwann cells leads to a modest motor function recovery after spinal cord injury (SMD = 0.85; 95% CI: 0.63–1.07; p < 0.001). Transplantation of these cells in acute phase of the injury (immediately after the injury) (OR = 4.30; 95% CI: 1.53–12.05; p = 0.007), application of mesenchymal/skin-derived precursors (OR = 2.34; 95% CI: 1.28–4.29; p = 0.008), and cells with human sources are associated with an increase in efficacy of Schwann cells (OR = 10.96; 95% CI: 1.49–80.77; p = 0.02). Finally, it seems thatthe efficacy of Schwann cells in mice is significantly lower than rats (OR = 0.03; 95% CI: 0.003–0.41; p = 0.009). Conclusion: Transplantation of Schwann cells can moderately improve motor function recovery. It seems that inter-species differences might exist regarding the efficacy of this cells. Therefore, this should be taken into account when using Schwann cells in clinical trials regarding spinal cord injuries

Histological Survey of the Effect of Granulocyte-colony-stimulating Factor(G-CSF) on Bacterial Translocation and Wound Healing in Burned Mice

Background: Burn wound is an important cause of morbidity and mortality worldwide. Improving the host's immune system and removing the infection can be effective in healing wounds caused by burns. Granulocyte-colony-stimulating factor (G-CSF) stimulates both the bone marrow to produce granulocytes and the function of neutrophil precursors. The aim of this study was to examine the effect of G-CSF on removing infection and healing wound. Materials and Methods: A burn model was used to induce burns in 18 adult Balb/c mice, and their wounds were infected by Acinetobacter baumannii strains. Burned mice were divided into two groups (control and G-CSF) and treated daily by subcutaneous injections of normal saline (0.1 mL) and G-CSF (10 μg/kg). The wound healing process was evaluated by the morphological and histological assessments. Results: In morphological assay, the mean size of the wounds in the 3rd and 7th days of the treatment was significantly lower in the G-CSF treated group compared to the control group. Some of the histological parameters were evaluated, including the level of inflammation, re-epithelialization, angiogenesis, collagen deposition, the amount of granulation tissue, and fibroblast maturation. The results showed that inflammation was reduced in the G-CSF-treated group, and re-epithelialization and collagen deposition were increased insignificantly compared to the normal saline-treated group. Furthermore, bacterial translocation was reduced significantly in the G-CSF-treated group. Conclusion: G-CSF enhances wound closure and helps in wound healing by improving the immune system. It has also an anti-inflammatory role and reduces bacterial translocation

Concentration-Effect Relationship of Intrapritoneal Administration of 1, 25 (OH) 2-Vitamin D in a Chronic Constriction Model of Neuropathic Pain

Introduction:  Results: These findings revealed the exaggerated responses in the group which received CCI. The group which was treated by 1 μg/kg of 1,25 vit D3 showed a significant reduction in pain behavior. Injection of 1,25 vit D3 did not change the response of animals to the acetone drop and von frey filament. Discussion: Our results showed that antinoceptive effect of 1,25 vit D3 in a rodent neuropathic pain model is dose dependent and this vitamin may provide new approach for treatment of chronic pain.The presence of nuclear receptors of 1,25 dihydroxy vitamin D3 (1,25 vit D3), the biologically active metabolite of vitamin D, in neurons and glial cells indicates the biological effect of this vitamin in the nervous system. The present experiment was conducted to identify the effects of different doses of 1,25 vit D3 on mechanical and cold allodynia in rodent model of neuropatinc pain. Methods: A mononeuropathy was produced by chronic constrictive injury (CCI) of the sciatic nerve. 1,25 vit D3 (0.3, 0.6 ,1 μg/Kg) was administered by an i.p. injection every 2 days during a month after CCI. Mechanical and cold allodynia were evaluated by Von frey filament and acetone respectively