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

Abstract

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.

Mesenchymal Stem Cells Reversed Morphine Tolerance and Opioid-induced Hyperalgesia

“…We chose to use MSCs because of their powerful paracrine functions, as shown in animal models of diseases such as traumatic brain injury15, peripheral neuropathy1617, and neuropathic pain18. Immunomodulatory and anti-inflammatory effects of MSCs were related to neuroprotection, neuroregeneration, and neuroneuromodulation in these studies.…”

Neuropathy and inflammation in diabetic bone marrow

“…The type of neuropathy (contusion, compression, transection, and ligation), the time between injury and intervention, and the number of transplanted cells impact the attenuation of allodynia after BM MSC transplantation. However, BM MSC transplantation has no effect on hyperalgesia unless it occurs during the first 4 days after injury (Figure , Table ) …”

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

“…Cellular therapies have shown favorable results and can be considered as a potential approach in treating neuropathic pain as shown in Table . MSCs from different sources or different routes have shown beneficial effects in reducing neuropathic pain in various animal models of allodynia and hyperalgesia (Franchi et al, ; Hosseini, Yousefifard, Aziznejad, & Nasirinezhad, ). The cell transplantation strategy for neuropathic pain treatment is based on its mediated analgesia and neuroprotective/regenerative potential.…”

“…MSCs therapy attenuates the production of TNF‐α and IL‐6 and increases the expression of the anti‐inflammatory cytokines such as through inhibiting the transcriptional factor NF‐κB (Du et al, ). Besides, BM‐MSCs have immunomodulatory properties that help in mending the redox imbalance, neuronal inflammation, and immune‐mediated injuries, as well as apoptosis (Hosseini et al, ; Jin et al, ).…”