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http://dx.doi.org/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, Shaghayegh (Institute de Biologie Structurale (IBS), Grenoble Alpes University, CEA, CNRS)
Maleki, Solmaz Nasseri (Physiology Research Center, Iran University of Medical Sciences)
Alavi, Seyedeh Niloufar Rafiei (Physiology Research Center, Iran University of Medical Sciences)
Neishaboori, Arian Madani (Physiology Research Center, Iran University of Medical Sciences)
Toloui, Amirmohammad (Physiology Research Center, Iran University of Medical Sciences)
Gubari, Mohammed I.M. (Department of Family and Community Medicine, College of Medicine, University of Sulaimani)
Sarveazad, Arash (Colorectal Research Center, Iran University of Medical Sciences)
Hosseini, Mostafa (Pediatric Chronic Kidney Disease Research Center, Tehran University of Medical Sciences)
Yousefifard, Mahmoud (Physiology Research Center, Iran University of Medical Sciences)
Publication Information
The Korean Journal of Pain / v.35, no.1, 2022 , pp. 43-58 More about this Journal
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.
Keywords
Bibliometrics; Cell Engineering; Chronic Pain; GABAergic Neurons; Gamma-Aminobutyric Acid; Hyperalgesia; Neural Stem Cells; Neuralgia; Pain Management; Spinal Cord Injuries;
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  • Reference
1 Finnerup NB. Pain in patients with spinal cord injury. Pain 2013; 154 Suppl 1: S71-6.   DOI
2 Sistrom CL, Mergo PJ. A simple method for obtaining original data from published graphs and plots. AJR Am J Roentgenol 2000; 174: 1241-4.   DOI
3 Wang D, Mou ZY, Zhai JX, Zong HX, Zhao XD. [Application of Stata software to test heterogeneity in meta-analysis method]. Zhonghua Liu Xing Bing Xue Za Zhi 2008; 29: 726-9. Chinese.
4 Etlin A, Braz JM, Kuhn JA, Wang X, Hamel KA, Llewellyn-Smith IJ, et al. Functional synaptic integration of forebrain GABAergic precursors into the adult spinal cord. J Neurosci 2016; 36: 11634-45.   DOI
5 Mukhida K, Mendez I, McLeod M, Kobayashi N, Haughn C, Milne B, et al. Spinal GABAergic transplants attenuate mechanical allodynia in a rat model of neuropathic pain. Stem Cells 2007; 25: 2874-85.   DOI
6 Bao S, Lv Z, Li Y, Ma J, Zhang Y, Li S, et al. Genetic engineering: pros versus cons in deciphering disease mechanism. Sci Insights 2016; 2016: e00258.
7 Tate DG, Forchheimer MB, Karana-Zebari D, Chiodo AE, Kendall Thomas JY. Depression and pain among inpatients with spinal cord injury and spinal cord disease: differences in symptoms and neurological function. Disabil Rehabil 2013; 35: 1204-12.   DOI
8 Sharp K, Boroujerdi A, Steward O, Luo ZD. A rat chronic pain model of spinal cord contusion injury. Methods Mol Biol 2012; 851: 195-203.   DOI
9 Whalley K. Pain: transplanted precursors halt neuropathic pain. Nat Rev Neurosci 2012; 13: 447.   DOI
10 Kumru H, Soler D, Vidal J, Navarro X, Tormos JM, PascualLeone A, et al. The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: an evoked potentials and quantitative thermal testing study. Eur J Pain 2013; 17: 55-66.   DOI
11 Backonja MM, Irving G, Argoff C. Rational multidrug therapy in the treatment of neuropathic pain. Curr Pain Headache Rep 2006; 10: 34-8.   DOI
12 Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers 2017; 3: 17002.   DOI
13 Meacham K, Shepherd A, Mohapatra DP, Haroutounian S. Neuropathic pain: central vs. peripheral mechanisms. Curr Pain Headache Rep 2017; 21: 28.   DOI
14 Jergova S, Gajavelli S, Varghese MS, Shekane P, Sagen J. Analgesic effect of recombinant GABAergic cells in a model of peripheral neuropathic pain. Cell Transplant 2016; 25: 629-43.   DOI
15 Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005; 118: 289-305.   DOI
16 Wolfe D, Mata M, Fink DJ. Targeted drug delivery to the peripheral nervous system using gene therapy. Neurosci Lett 2012; 527: 85-9.   DOI
17 McLeod MC, Kobayashi NR, Sen A, Baghbaderani BA, Sadi D, Ulalia R, et al. Transplantation of GABAergic cells derived from bioreactor-expanded human neural precursor cells restores motor and cognitive behavioral deficits in a rodent model of Huntington's disease. Cell Transplant 2013; 22: 2237-56.   DOI
18 Shetty AK, Bates A. Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer's and Parkinson's diseases. Brain Res 2016; 1638(Pt A): 74-87.   DOI
19 Marineo G, Iorno V, Gandini C, Moschini V, Smith TJ. Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial. J Pain Symptom Manage 2012; 43: 87-95.   DOI
20 Eaton MJ, Martinez MA, Karmally S. A single intrathecal injection of GABA permanently reverses neuropathic pain after nerve injury. Brain Res 1999; 835: 334-9.   DOI
21 Jergova S, Gajavelli S, Pathak N, Sagen J. Recombinant neural progenitor transplants in the spinal dorsal horn alleviate chronic central neuropathic pain. Pain 2016; 157: 977-89.   DOI
22 IntHout J, Ioannidis JP, Borm GF. The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. BMC Med Res Methodol 2014; 14: 25.   DOI
23 Hwang I, Hahm SC, Choi KA, Park SH, Jeong H, Yea JH, et al. Intrathecal transplantation of embryonic stem cell-derived spinal GABAergic neural precursor cells attenuates neuropathic pain in a spinal cord injury rat model. Cell Transplant 2016; 25: 593-607.   DOI
24 Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE's risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14: 43.   DOI
25 Wei D, Tang K, Wang Q, Estill J, Yao L, Wang X, et al. The use of GRADE approach in systematic reviews of animal studies. J Evid Based Med 2016; 9: 98-104.   DOI
26 Polgar E, Todd AJ. Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA(A) receptors from synapses in laminae I-II of the ipsilateral spinal dorsal horn. Neuroscience 2008; 156: 193-202.   DOI
27 Eaton MJ, Plunkett JA, Martinez MA, Lopez T, Karmally S, Cejas P, et al. Transplants of neuronal cells bioengineered to synthesize GABA alleviate chronic neuropathic pain. Cell Transplant 1999; 8: 87-101.   DOI
28 Braz JM, Sharif-Naeini R, Vogt D, Kriegstein A, Alvarez-Buylla A, Rubenstein JL, et al. Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain. Neuron 2012; 74: 663-75.   DOI
29 Braz JM, Wang X, Guan Z, Rubenstein JL, Basbaum AI. Transplant-mediated enhancement of spinal cord GABAergic inhibition reverses paclitaxel-induced mechanical and heat hypersensitivity. Pain 2015; 156: 1084-91.   DOI
30 Eaton MJ, Berrocal Y, Wolfe SQ. Potential for cell-transplant therapy with human neuronal precursors to treat neuropathic pain in models of PNS and CNS injury: comparison of hNT2.17 and hNT2.19 cell lines. Pain Res Treat 2012; 2012: 356412.   DOI
31 Jergova S, Hentall ID, Gajavelli S, Varghese MS, Sagen J. Intraspinal transplantation of GABAergic neural progenitors attenuates neuropathic pain in rats: a pharmacologic and neurophysiological evaluation. Exp Neurol 2012; 234: 39-49.   DOI
32 Juarez-Salinas DL, Braz JM, Etlin A, Gee S, Sohal V, Basbaum AI. GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness. Brain 2019; 142: 2655-69.   DOI
33 Kim DS, Jung SJ, Nam TS, Jeon YH, Lee DR, Lee JS, et al. Transplantation of GABAergic neurons from ESCs attenuates tactile hypersensitivity following spinal cord injury. Stem Cells 2010; 28: 2099-108.   DOI
34 Vaysse L, Sol JC, Lazorthes Y, Courtade-Saidi M, Eaton MJ, Jozan S. GABAergic pathway in a rat model of chronic neuropathic pain: modulation after intrathecal transplantation of a human neuronal cell line. Neurosci Res 2011; 69: 111-20.   DOI
35 Manion J, Khuong T, Harney D, Littleboy JB, Ruan T, Loo L, et al. Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain. Pain 2020; 161: 379-87.   DOI