Clinical significance of methyl-CpG binding protein 2 in postherpetic neuralgia: an observational study.

Importancia clínica de la proteína 2 de unión a metil-CpG (MECP2) en la neuralgia posherpética: un estudio observacional.

• Zhijian Wang Nanchang University, Nanchang, China. https://orcid.org/0000-0001-6086-2241
• Wei Shen Nanchang University, Nanchang, China. https://orcid.org/0000-0003-0342-3634
• Mengye Zhu Nanchang University, Nanchang, China. https://orcid.org/0000-0002-6081-4490
• Mu Xu Nanchang University, Nanchang, China. https://orcid.org/0000-0002-9755-3028
• Mizhen Qiu Nanchang University, Nanchang, China. https://orcid.org/0000-0002-1066-1908
• Daying Zhang Nanchang University, Nanchang, China. https://orcid.org/0000-0003-0975-9964
• Shibiao Chen Nanchang University, Nanchang, China. https://orcid.org/0000-0002-5622-1860

DOI: https://doi.org/10.54817/IC.v63n1a07

Keywords: MECP2, postherpetic neuralgia, inflammatory factors, quality of life

Abstract

The present study was aimed to investigate the clinical significance of methyl-CpG binding protein 2 (MECP2) in patients with postherpetic neuralgia (PHN). This prospective case control study enrolled 319 cases of PHN patients from April 2017~December 2019. The patients’ sleep quality and quality of life were evaluated using the Pittsburgh sleep quality score and the SF-36 scale, respectively. The serum levels of MECP2, CRP, IL-6 and TNF-α were tested using enzyme linked immunosorbent assay (ELISA). The pain condition of the patients was evaluated using the visual analogue scale (VAS). The levels of MECP2 were significantly increased in PHN patients compared with the patients without PHN. Serum MECP2 levels were the highest in patients with severe pain, and were the lowest in patients with mild pain. Similarly, the frequency of severe pain in patients with low expression of MECP2 was significantly lower than the patients with higher MECP2 expression. Besides, serum levels of inflammatory factors CRP, IL-6 and TNF-α were markedly increased in PHN patients, which were also increased with the increase of the severity of pain. CRP, IL-6 and TNF-α were positively correlated with serum levels of MECP2 in PHN patients. Before the study, patients with lower MECP2 levels showed a significantly higher SF-36 score and lower Pittsburgh and VAS scores than patients with higher levels of MECP2. However, after one month, no significant difference was found between the patients. ROC curve showed MECP2 had the potential as a diagnostic biomarker for PHN. In conclusion, higher serum MECP2 levels are associated with a more severe pain condition and increased release of inflammatory factors.

References

Mallick-Searle T, Snodgrass B, Brant JM. Postherpetic neuralgia: epidemiology, pathophysiology, and pain management pharmacology. J Multidiscip Health 2016;9:447.

Shrestha M, Chen A. Modalities in managing postherpetic neuralgia. Korean J Pain 2018;31(4):235.

Saguil A, Kane SF, Mercado MG, Lauters R. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician 2017;96(10):656-663.

Gudin J, Fudin J, Wang E, Haylon T, Patel K, Goss TF. Treatment patterns and medication use in patients with postherpetic neuralgia. J Manag Care Spec Ph 2019;25(12):1387-1396.

Wei S, Li X, Wang H, Liu Q, Shao L. Analysis of the risk factors for postherpetic neuralgia. Dermatology 2019;235(5):426-433.

Saguil A, Kane S, Mercado M, Lauters R. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician 2017 15;96(10):656-663.

Johnson RW, Rice ASC. Postherpetic neuralgia. New Engl J Med 2014;371(16):1526- 1533.

Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C. CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet 2005;14(14):1935-1346.

Downs J, Géranton SM, Bebbington A, Jacoby P, Bahi-Buisson N, Ravine D, Leonard H. Linking MECP2 and pain sensitivity: the example of Rett syndrome. Am J Med Genet A. 2010;152(5):1197-1205.

Zhang W, Peterson M, Beyer B, Frankel WN, Zhang Z-W. Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. J Neurosci 2014;34(7):2754-2763.

Bodda C, Tantra M, Mollajew R, Arunachalam JP, Laccone FA, Can K, Rosenberger A, Mironov SL, Ehrenreich H, Mannan AU. Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures. Am J Pathol 2013;183(1):195-210.

Rzeszotarska E, Sowinska A, Stypinska B, Walczuk E, Wajda A, Lutkowska A, Felis-Giemza A, Olesinska M, Puszczewicz M, Majewski D, Jagodzinski PP, Czerewaty M, Malinowski D, Pawlik A, Jaronczyk M, Paradowska-Gorycka A. The role of MECP2 and CCR5 polymorphisms on the development and course of systemic lu- pus erythematosus. Biomolecules 2020, 10(3):494. doi: 10.3390/biom10030494.

Xie AX, Pan X-Q, Meacham RB, Malykhina AP. The expression of transcription factors Mecp2 and CREB Is modulated in inflammatory pelvic pain. Front Syst Neurosci 2019;12:69.

Manners MT, Tian Y, Zhou Z, Ajit SK. MicroRNAs downregulated in neuro- pathic pain regulate MeCP2 and BDNF related to pain sensitivity. FEBS Open Bio 2015;5:733-740.

Branch HzecwgoCMDAD. Chinese Consensus of Herpes Zoster. Chin J Dermatol 2018;51:403–408.

Yu S, Wan Y, Wan Q. Chinese expert consensus on diagnosis and treatment of postherpetic neuralgia. Chin J Pain Med 2016;22:161-167.

Wang Y, Liu C, Guo Q-L, Yan J-Q, Zhu X-Y, Huang C-S, Zou W-Y. Intrathecal 5-azacytidine inhibits global DNA methylation and methyl-CpG-binding protein 2 expression and alleviates neuropathic pain in rats following chronic constriction injury. Brain Res 2011;1418:64-69.

Van Der Vaart M, Svoboda O, Weijts BG, Espín-Palazón R, Sapp V, Pietri T, Bagnat M, Muotri AR, Traver D. Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation. Dis Model Mech 2017;10(12):1439-1451.

Li C, Jiang S, Liu S-Q, Lykken E, Zhao L-t, Sevilla J, Zhu B, Li Q-J. MeCP2 enforces Foxp3 expression to promote regulatory T cells’ resilience to inflammation. Proc Natl Acad Sci 2014;111(27):E2807- E2816.

Ma T-t, Li X-f, Li W-x, Yang Y, Huang C, Meng X-m, Zhang L, Li J. Geniposide alleviates inflammation by suppressing MeCP2 in mice with carbon tetrachloride- induced acute liver injury and LPS-trea- ted THP-1 cells. Int Immunopharmacol 2015;29(2):739-747.

Wittrahm R, Takalo M, Marttinen M, Kuulasmaa T, Mäkinen P, Kemppainen S, Martiskainen H, Rauramaa T, Pike I, Leinonen V. MECP2 Increases the pro-inflammatory response of microglial cells and phospho-rylation at serine 423 regulates neuronal gene expression upon neuroinflammation. Cells 2021;10(4):860.

Zhang R, Huang M, Cao Z, Qi J, Qiu Z, Chiang L-Y. MeCP2 plays an analgesic role in pain transmission through regulating CREB/miR-132 pathway. Mol Pain 2015;11:s12990-015.

Zalosnik MI, Fabio MC, Bertoldi ML, Castañares CN, Degano AL. MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge. Sci Rep 2021;11(1):1-15.

Zhao W, Wang Y, Fang Q, Wu J, Gao X, Liu H, Cao L, An J. Changes in neurotrophic and inflammatory factors in the cerebrospinal fluid of patients with postherpetic neuralgia. Neurosci Lett 2017;637:108-113.

Cao S, Zhang D, Yuan J, Deng W, Wen S, Qin B, Li Y. Inflammatory cytokine expression in the skin of patients with postherpetic neuralgia. J Int Med Res 2020;48(8):0300060520929582.

Üçeyler N, Valet M, Kafke W, Tölle TR, Sommer C. Local and systemic cytokine expression in patients with postherpetic neuralgia. PLoS One 2014;9(8):e105269.