The efficacy of GABAergic precursor cells transplantation in alleviating neuropathic pain in animal models: a systematic review and meta-analysis

Abstract

Background: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. Methods: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). Results: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia.Conclusions: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

The Effect of GABAergic Cells Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review With Meta-Analysis

“…Although, similar study had been published ( 53 ), our meta-analysis is not redundant. We set stricter inclusion and exclusion criteria to ensure the consistency of studies, the included studies were not completely consistent, and sensitivity and publication bias could not be assessed.…”

Cell therapy for neuropathic pain

“…The optimal volume of transplanted cells is unknown, likely ranging from 1 × 10 5 to 6 × 10 6 cell dose/kg with different animal (Wang et al, 2020) found that the number of transplanted cells was seemingly related to animal models and routes of administration. While more studies found that there existed a dose-dependency between the degree of pain relief from cell therapy and the amount of engrafted cells irrespective of central nerve injury or peripheral nerve injury, with a median number of transplanted cells being 3 × 10 6 cell dose/kg (Hosseini et al, 2015;Han et al, 2019;Askarian-Amiri et al, 2022).…”

Spinal Cord Injury Provoked Neuropathic Pain and Spasticity, and Their GABAergic Connection

“…It also suggests that although there are possibilities of genetic defects with genetically modified cells, they are still the best sources for alleviating NP compared to GABAergic cells and stem cells. 106 Studies also report the beneficial effects of bone marrow-derived mesenchymal stem cells (BMSCs) in reducing post-SCI NP and promoting sensory recovery. BMSCs showed effects by inhibiting the activation of MAPK signaling pathway mediated neuronal hyperexcitability.…”

“…Additionally, intraspinal transplantation produces more significant effects than intrathecal transplantation. It also suggests that although there are possibilities of genetic defects with genetically modified cells, they are still the best sources for alleviating NP compared to GABAergic cells and stem cells [ 106 ].…”