Korean J Pain.  2022 Jan;35(1):43-58. 10.3344/kjp.2022.35.1.43.

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

• Askarian-Amiri S
• Maleki SN
• Alavi SNR
• Neishaboori AM
• Toloui A
• Gubari MIM
• Sarveazad A
• Hosseini M
• Yousefifard M

• KMID: 2524646
• DOI: http://doi.org/10.3344/kjp.2022.35.1.43

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.

Keyword

Bibliometrics; Cell Engineering; Chronic Pain; GABAergic Neurons; Gamma-Aminobutyric Acid; Hyperalgesia; Neural Stem Cells; Neuralgia; Pain Management; Spinal Cord Injuries

Figure

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  Fig. 1 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram of present study.

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  Fig. 2 Publication bias assessment across included studies. CI: confidence interval.

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  Fig. 3 Forest plot of GABAergic cell transplantation on improvement of allodynia. Since, some included studies had more than one experiment, the number of experiments exceeded the number of studies. CI: confidence interval, SD: standard deviation.

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  Fig. 4 Forest plot of GABAergic cell transplantation on improvement of hyperalgesia. Since, some included studies had more than one experiment, the number of experiments exceeded the number of studies. CI: confidence interval, SD: standard deviation.

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  Fig. 5 Sensitivity analysis to assess individual studies’ effect on efficacy of GABA cell transplantation on improvement of allodynia. Since, some included studies had more than one experiment, the number of experiments exceeded the number of studies. CI: confidence interval.

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  Fig. 6 Sensitivity analysis to assess individual studies’ effect on efficacy of GABA cell transplantation on improvement of hyperalgesia. Since, some included studies had more than one experiment, the number of experiments exceeded the number of studies. CI: confidence interval.

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