Invest Clin 63(1): 81 - 91, 2022 https://doi.org/10.54817/IC.v63n1a07

Corresponding Author: Shibiao Chen, Department of Anesthesiology, the First Affiliated Hospital of Nanchang

University, Nanchang 330006, China. Tel.: 86-0791-88692578. Email: sbiao_ch0211@126.com

Clinical significance of methyl-CpG binding

protein 2 in postherpetic neuralgia:

an observational study.

Zhijian Wang1, Wei Shen1, Mengye Zhu1, Mu Xu1, Mizhen Qiu1, Daying Zhang1

and Shibiao Chen2

1Department of Pain, the First Affiliated Hospital of Nanchang University, Nanchang,

China.

2Department of Anesthesiology, the First Affiliated Hospital of Nanchang University,

Nanchang, China.

Key words: MECP2; postherpetic neuralgia; inflammatory factors; quality of life.

Abstract. The present study was aimed to investigate the clinical signifi-

cance 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 qual-

ity 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 lev-

els 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 fre-

quency of severe pain in patients with low expression of MECP2 was significant-

ly 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 sig-

nificantly higher SF-36 score and lower Pittsburgh and VAS scores than patients

with higher levels of MECP2. However, after one month, no significant differ-

ence was found between the patients. ROC curve showed MECP2 had the po-

tential 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.

82 Wang et al.

Investigación Clínica 63(1): 2022

Importancia clínica de la proteína 2 de unión a metil-CpG

(MECP2) en la neuralgia posherpética: un estudio observacional.

Invest Clin 2022; 63 (1): 81 – 91

Palabras clave: MECP2; neuralgia posherpética; factores inflamatorios; calidad de vida.

Resumen. El objetivo de este estudio fue investigar la importancia clínica

de la MECP2 en pacientes con neuralgia posherpética (NPH). Este estudio ob-

servacional prospectivo incluyó 319 pacientes con NPH entre abril de 2017 y

diciembre de 2019. La calidad del sueño y la calidad de vida de los pacientes se

evaluaron con la escala de calidad del sueño de Pittsburgh y la escala SF - 36,

respectivamente. Los niveles séricos de MECP2, PCR, IL-6 y TNF-α fueron de-

terminados por ELISA. Se utilizó la escala visual analógica (EVA) para evaluar la

intensidad del dolor. Los niveles de MECP2 en pacientes con NPH aumentaron

significativamente en comparación con los pacientes sin NPH. El nivel sérico de

MECP2 fue más alto en pacientes con dolor grave y el más bajo en pacientes con

dolor leve. Además, la incidencia de dolor grave en pacientes con baja expresión

de MECP2 fue significativamente menor que en pacientes con alta expresión

de MECP2. Además, los niveles séricos de PCR, IL-6 y TNF-α aumentaron sig-

nificativamente en pacientes con NPH, y se incrementaron con el aumento del

grado de dolor. Los niveles séricos de PCR, IL-6 y TNF-α en pacientes con NPH

se correlacionaron positivamente con los niveles séricos de MECP2. Antes del

estudio, los pacientes con niveles más bajos de MECP2 tenían puntuaciones

significativamente más altas de SF - 36, y puntuaciones más bajas de Pittsburgh

y EVA que los pacientes con niveles más altos de MECP2. Sin embargo, no se

encontraron diferencias significativas entre los pacientes un mes después. Las

curvas ROC mostraron que la MECP2 podría ser un biomarcador de diagnóstico

para la NPH. En general, los niveles séricos más altos de la MECP2 se asociaron

con condiciones de dolor más graves y un aumento de la liberación de factores

inflamatorios.

Received: 11-08-2021 Accepted: 30-10-2021

INTRODUCTION

Postherpetic neuralgia (PHN) is a com-

mon complication after an acute episode of

herpes zoster, with an estimated incidence

of 5~20% in herpes zoster patients, espe-

cially in elderly patients 1-3. Studies report

that PHN can last for months to years, se-

riously affecting people’s quality of life 4.

There are many risk factors to influence the

incidence of PHN 5. Generally, the PHN is

thought to be due to the immune/inflamma-

tory response by the reactivation and migra-

tion of varicella zoster virus 6,7. Since pain

is the most common symptom of PHN, both

inflammation and pain related factors are of

great significance in PHN investigation.

Methyl-CpG binding protein 2 (MECP2),

a kind of protein that can bind methylated

DNA, is thought to play important roles in

nervous system diseases like seizure 8, and is

also associated with pain 9. It is found that the

deficiency of MECP2 in forebrain excitatory

neurons could lead to cortical hyperexcita-

tion and seizures 10. However, overexpression

of MECP2 resulted in higher susceptibility

MECP2 in postherpetic neuralgia 83

Vol. 63(1): 81 - 91, 2022

toward seizures 11. Furthermore, MECP2 is

found to be elevated in several pain and in-

flammation conditions 12, 13. Generally, an

increased MECP2 level is accompanied with

nerve injury, like dorsal root ganglia injury

and increased pain sensitivity 14. However, up

to now, there is no study focusing on the role

of MECP2 in PHN.

In the present study, we performed a

prospective observational research to inves-

tigate the clinical significance of MECP2 in

PHN patients. This study might provide a

new research target and biomarker for PHN.

MATERIAL AND METHODS

Patients

This prospective observational study en-

rolled 319 patients with and without posther-

petic neuropathy from April 2017~December

2019. The diagnosis of herpes zoster was es-

tablished according to the Chinese Consen-

sus of Herpes Zoster 15. The diagnosis of PHN

was determined according to the Chinese ex-

pert consensus on diagnosis and treatment of

postherpetic neuralgia 16. Briefly, the herpes

zoster diagnostic criteria were defined as pa-

tients with irregular erythema occurred in a

certain nerve distribution area, followed by

a majority or cluster of millet to mung bean

sized herpes, which quickly turned into blis-

ters and was accompanied by neuralgia. The

diagnostic criteria of PHN were defined as af-

ter the skin lesions of herpes zoster subsided,

the patient developed local pain, pruritus and

paresthesia for more than one month. The

inclusion criteria were: 1) all patients were

diagnosed as PHN according to the above

criteria and didn’t receive any treatment be-

fore; 2) the patients showed abnormal pain

and touch feeling distributed by innervation

area and sometimes showed skin pigmenta-

tion; 3) the pain types were as sharp pain or

persistent burning pain, or tight bundle pain;

and 4) patients showed other discomfort on

lesion position after nerve injury, including

itching, tight feeling and ant feeling. The fol-

lowing patients were excluded: 1) patients

with severe inflammation diseases, such as

pneumonia; 2) patients with fractures or

other severe system diseases like myocardial

infarction or stroke within three months be-

fore the study; 3) patients with other neu-

ralgia like intercostal neuralgia, cephalalgia

nervosa, post-stroke neuralgia, etc. All pa-

tients received routine strategy therapy in-

cluding anti-pain treatment like treatment

with pregabalin (150 mg×2/d for 14 d) or

carbamazepine (100 mg/d for 14 d), and the

grade of pain was recorded by the patients in

awake state. Additionally, serum samples and

medical records were collected from the 319

herpes zoster patients whose skin lesions of

herpes zoster subsided without PHN. The in-

clusion of herpes zoster patients without PHN

was according to the above diagnostic criteria

of herpes zoster as well as the above inclu-

sion criteria. All participants signed a written

informed consent. The ethic approval was ob-

tained from the Ethic Committee of the First

Affiliated Hospital of Nanchang University

and a written informed consent was obtained

from all patients.

Measurement of MECP2 and inflammatory

factors

Blood samples of all PHN patients were

collected at the day they came to the out-

patient department. The samples were col-

lected in tubes without anticoagulant and

were centrifuged at 12000 g for 20 min.

The serum levels of MECP2, CRP, IL-6 and

TNF-α were tested using commercially avail-

able enzyme linked immunosorbent assay

(ELISA) kits according to the manufactur-

er’s instructions. The kits used were MECP2

(MYBioSource, cat. No. MBS2515729),

CRP (BOSTER Bio, cat. No. EK1316), IL-6

(BOSTER Bio, cat. No. EK0410) and TNF-α

(BOSTER Bio, cat. No. EK0525).

Data collection

The pain condition of patients was evalu-

ated at the time of diagnosis using the visual

analogue scale (VAS). The severity of the pain

condition of PHN patients were defined as: mild

84 Wang et al.

Investigación Clínica 63(1): 2022

VAS 1~3, moderate VAS 4~6, or severe VAS

7~10. Patient’s demographic data including

age, sex, BMI, complications, and clinical char-

acteristics including disease course, rash types

and sites of skin involvement, were collected.

The patients’ sleep quality and quality of life

were evaluated using the Pittsburgh sleep qual-

ity score and the SF-36 scale before the study

and after one month of treatment, respectively.

Statistical analysis

All data distributed normally were ex-

pressed by means ± SD. The distribution

of the data was analyzed by Kolmogorov-

Smirnov method. Comparison between the

two groups was conducted by t test and com-

parison among three or more groups was

performed using one-way analysis of variance

(ANOVA) followed by Tukey post hoc test.

Rates were compared by Chi square test.

ROC curve was used for diagnostic value

of MECP2 in PHN patients. All calculation

was performed using SPSS 18.0 (SPSS Inc.,

Chicago, USA) and GraphPad 6.0 (GraphPad

Software, San Diego, CA, USA).

RESULTS

MECP2 was upregulated in PHN patients

The basic clinical characteristics of all pa-

tients are listed in Table 1. There were no sig-

nificant differences in age, sex, BMI and com-

plications between the PHN patients and the

controls. The mean VAS score of all PHN pa-

tients was 3.38±2.26. Serum levels of MECP2

were determined in PHN patients and the her-

pes zoster patients without PHN. It was found

that the levels of MECP2 were significantly in-

creased in PHN patients when compared with

the non-PHN patients (P<0.05, Fig. 1).

Table 1

Basic characteristics of all participants.

Variables PHN, n=319 non-PHN, n=319 P value

Age, y 58.32±8.71 58.71±8.88 0.571

Sex, male (%) 179 (56.11) 170 (53.29) 0.689

BMI, kg/m225.33±3.81 25.34±3.79 0.985

Complications, n (%) 0.848

Diabetes 33 (10.34) 38 (11.91)

Hypertension 56 (17.55) 47 (14.73)

Current smoker 112 (35.11) 108 (33.86)

Disease course (PHN), Mon 4.40±1.12 -

Sites of skin involvement, n (%) 0.908

Lumbosacral nerve area 154 (48.28) 161 (50.47)

Intercostal nerve area 61 (19.12) 52 (16.30)

Trigeminal nerve area 43 (13.48) 37 (11.60)

Brachial plexus area 25 (7.84) 30 (9.40)

Perineal nerve area

VAS score 3.38±2.26 -

Distribution of VAS score, n (%)

Mild 152 (47.65) -

Moderate 98 (30.72) -

Severe 69 (21.63) -

MECP2 in postherpetic neuralgia 85

Vol. 63(1): 81 - 91, 2022

MECP2 was positively correlated with pain

severity of PHN patients

Then, levels of MECP2 were detected in

PHN patients with different pain severities.

As shown in Fig. 2, serum MECP2 levels were

the highest in patients with severe pain, and

were the lowest in patients with mild pain,

and the difference was significant between

the groups (P<0.05). The patients were then

further divided into high MECP2 expression

group and low MECP2 expression group ac-

cording to the mean serum levels in PHN pa-

tients (45.83 ng/mL). It was found that the

frequency of severe pain in patients with low

expression of MECP2 was significantly lower

than the patients with higher MECP2 expres-

sion (P<0.05, Table 2). Notably, patients

with mild pain were found to be markedly de-

creased in patients with higher MECP2 than

patients with higher MECP2 (P<0.05).

Relationship between MECP2 and

inflammatory factors in PHN patients

To further investigate the role of

MECP2 in PHN, the serum levels of inflam-

matory factors CRP, IL-6 and TNF-α were de-

termined. It was found all these factors were

markedly increased in PHN patients com-

pared with the no-PHN patients (P<0.05,

Fig. 3), and serum levels of CRP, IL-6 and

TNF-α increased with the severity of pain in

PHN patients (P<0.05), except for the differ-

ence of TNF-α between severe and moderate

pain. The Pearson’s correlation test showed

that CRP, IL-6 and TNF-α were positively cor-

related with serum levels of MECP2 in PHN

patients (P<0.05, Table 3).

Association between MECP2 and quality

of life of PHN patients

The Pittsburgh sleep quality score and

the SF-36 scale, as well as the VAS score were

then evaluated before the study and after

one month of treatment. It was found that

before study, patients with lower MECP2 lev-

els showed significantly higher SF-36 score

and lower Pittsburgh and VAS scores than

patients with higher MECP2 (P<0.05, Table

4). However, after one month, no significant

differences were found between the patients.

Diagnostic value of MECP2 in PHN

Finally, we determined the diagnostic

value of MECP2 for PHN in herpes zoster

Serum MECP2 (ng/ml)

PHN

non-PHN

***

Fig. 1. Serum levels of MECP2 in PHN patients and the non-PHN.

86 Wang et al.

Investigación Clínica 63(1): 2022

patients. It was found that MECP2 has the

potential as a biomarker for PHN diagnosis,

with a ROC curve ACU, cutoff value 33.56

ng/mL, sensitivity 70.5%, specificity 65.5%

(Fig. 4).

DISCUSSION

Postherpetic neuralgia is a common

complication after treatment of herpes zos-

ter and may decrease the patients’ quality

of life. Since the prevention of PHN is an ef-

fective method to reduce the patients’ pain

after herpes zoster, biomarkers for diagnosis

and prediction of PHN are also important.

In the present study, we demonstrated that

serum MECP2 was up-regulated in PHN pa-

tients and higher MECP2 was associated with

a more severe pain condition, higher levels

of inflammatory factors, and lower quality of

life before treatment.

Rzeszotarska have reported that MECP2

is a factor associated with both inflammatory

factors and pain 12. Generally, most studies

found that increased MECP2 is associated

with increased pain sensitivity and increased

pro-inflammatory factors. It was found in

the mouse chronic pain model, that MECP2

was increased in S1 glutamate (GluS1) neu-

rons and increased MECP2 was associated

with increased neuronal activity and knock-

down of MECP2 diminished the offspring

pain sensitization, which was increased by

overexpressing MECP2. In 2,4,6-trinitroben-

zenesulfonic acid-induced- pelvic inflamma-

tion pain in a rat model, MECP2 was also

Serum MECP2 (ng/ml)

M ild

Moderate

Severe

100

150

***

Fig. 2. Serum levels of MECP2 in patients with different pain severity.

Table 2

Pain severity in PHN patients with different expression of MECP2.

Variables Low MECP2, n=173 High MECP2, n=146 P value

VAS distribution, n (%) <0.0001

Mild 113 (65.32) 39 (26.71)

Moderate 43 (24.86) 55 (37.67)

Severe 17 (9.83) 52 (35.62)

MECP2 in postherpetic neuralgia 87

Vol. 63(1): 81 - 91, 2022

found to be overexpressed in neurons and

the increased MECP2 was accompanied with

increased cAMP response element-binding

protein 13. In chronic constriction injury,

global DNA methylation and MeCP2 expres-

sion were both increased in the rats’ spinal

cord, which could be decreased by intrathe-

cal 5-azacytidine 17. Besides, the deficiency of

MECP2 resulted in an increase in neutrophil

infiltration and anti-inflammatory factor

IL-10, as well as decreased level of TNF-α 18.

The inhibition of MECP2 was also found to

alleviate inflammation, while overexpression

of MECP2 promoted inflammation response

in different kinds of cells 19-21. However, sev-

eral studies also found positive results, dem-

onstrating overexpression of MECP2 led to

decreased acute mechanical pain, thermal

pain in acute pain transduction and over-

expression improved neuropathic pain 22. In

Rett syndrome, mutation and duplication of

MECP2 both induce decreased pain sensitiv-

ity 9. Besides, MECP2 deficiency might also

exacerbate neuroinflammatory setting and

autoreactive response during an autoim-

mune challenge 23. In the present study, we

observed that serum MECP2 was up-regulat-

ed in PHN patients and was associated with

Fig. 3. Serum levels of CRP, IL-6 and TNF-α in non-PHN patients and PHN patients with different pain severity.

Table 3

Correlation between MECP2 and inflammatory

factors in PHN patients.

Factors Pearson’ correlation P value

CRP 0.495 <0.001

IL-6 0.471 <0.001

TNF-α0.354 <0.001

88 Wang et al.

Investigación Clínica 63(1): 2022

patients’ release of inflammatory factors

and pain condition, which was consistent

with most of the above researches. Since

the relationship between MECP2 and pain

remains controversial, the elevated MECP2

can be either as a pro-inflammatory factor

or a compensatory mechanism to reduce

inflammation and pain. In both of the two

conditions, MECP2 can be increased in pain

and inflammation. However, this specula-

tion needs more studies to further confirm.

Besides, we also found that serum MECP2

was associated with patients’ quality of life

before study. However, different levels of

MECP2 didn’t influence the quality of life af-

ter one-month treatment.

Inflammation is closely related to the

pain, including correlated with PHN. It was

reported that PHN patients showed higher

levels of IL-1β and lower levels of BDNF in ce-

rebrospinal fluid 24. Another study found the

expression of IL-1α, IL-16, intercellular ad-

hesion molecule-1, and monocyte chemoat-

tractant protein-1 was elevated in skin of

PHN patients 25. Besides, Üçeyler et al. dem-

onstrated that in some PHN patients, the ex-

Table 4

Association between MECP2 and quality of life of PHN patients.

Variables Low MECP2, n=173 High MECP2, n=146 P value

VAS Before 3.38±2.26 5.40±2.54 <0.0001

After 1 month 1.99±0.63 2.11±0.65 0.0958

SF-36 Before 63.87±7.87 62.01±8.39 0.0422

After 1 month 73.13±7.45 73.12±7.00 0.9902

Pittsburgh score Before 12.30±2.47 13.78±2.78 <0.0001

After 1 month 7.80±4.55 7.63±4.14 0.7293

Fig. 4. ROC curve for diagnostic value of MECP2 in PHN.

MECP2 in postherpetic neuralgia 89

Vol. 63(1): 81 - 91, 2022

pression of IL-10 and IL-6 on skin might in-

crease than unaffected skin 26. In our study,

we also found that inflammatory factors

CRP, IL-6 and TNF-α were increased in PHN

patients. Besides, we demonstrated that se-

rum MECP2 levels were positively correlated

with serum inflammatory factors. All these

results indicated that increased MECP2 was

correlated with increased inflammation and

pain of PHN patients.

The present study includes some limi-

tations, The VAS scale and Pittsburg sleep

quality are subjective scales, these factors

depended of the subjective appreciation of

the individual, so there was no confirmation

that the levels of MECP2 correspond to the

exact grade of pain because each subject

can express the pain sensation in differ-

ent form and may be an inexact measure of

pain´s classification. In addition, the sam-

ple size of the study is small and we didn’t

investigate the molecular mechanism for

MECP2 in PHN, and how the phosphorylat-

ed-MECP2 changes is also unclear, which

need further investigations to reveal.

In conclusion, this observational study

demonstrated that higher serum MECP2 lev-

els were associated with a more severe pain

condition and increased release of inflam-

matory factors, as well as a poorer quality of

life of PHN patients before treatment. This

study provided a novel potential biomarker

for diagnosis of PHN.

ACKNOWLEDGEMENTS

We would like to acknowledge the ever-

yone for their helpful contributions on this

paper.

Funding

Science and Technology Project of Jiangxi

Provincial Health Commission (220211509).

Declaration of conflict of interest

All authors declare no conflict of interest.

Authors’ ORCID numbers

• Zhijian Wang

0000-0001-6086-2241

• Wei Shen

0000-0003-0342-3634

• Mengye Zhu

0000-0002-6081-4490

• Mu Xu

0000-0002-9755-3028

• Mizhen Qiu

0000-0002-1066-1908

• Daying Zhang

0000-0003-0975-9964

• Shibiao Chen

0000-0002-5622-1860

Authors’ contributions

Each author has made an important

scientific contribution to the study and has

assisted with the drafting or revising of the

manuscript.

REFERENCES

1. Mallick-Searle T, Snodgrass B, Brant

JM. Postherpetic neuralgia: epidemiolo-

gy, pathophysiology, and pain manage-

ment pharmacology. J Multidiscip Health

2016;9:447.

2. Shrestha M, Chen A. Modalities in mana-

ging postherpetic neuralgia. Korean J Pain

2018;31(4):235.

3. Saguil A, Kane SF, Mercado MG, Lauters

R. Herpes zoster and postherpetic neural-

gia: prevention and management. Am Fam

Physician 2017;96(10):656-663.

4. Gudin J, Fudin J, Wang E, Haylon T, Pa-

tel K, Goss TF. Treatment patterns and

medication use in patients with posther-

petic neuralgia. J Manag Care Spec Ph

2019;25(12):1387-1396.

5. Wei S, Li X, Wang H, Liu Q, Shao L. Analy-

sis of the risk factors for postherpetic neu-

ralgia. Dermatology 2019;235(5):426-433.

90 Wang et al.

Investigación Clínica 63(1): 2022

6. Saguil A, Kane S, Mercado M, Lauters R.

Herpes zoster and postherpetic neuralgia:

prevention and management. Am Fam Phy-

sician 2017 15;96(10):656-663.

7. Johnson RW, Rice ASC. Postherpetic neu-

ralgia. New Engl J Med 2014;371(16):1526-

1533.

8. 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.

9. Downs J, Géranton SM, Bebbington A, Ja-

coby 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.

10. Zhang W, Peterson M, Beyer B, Frankel

WN, Zhang Z-W. Loss of MeCP2 from fore-

brain excitatory neurons leads to cortical

hyperexcitation and seizures. J Neurosci

2014;34(7):2754-2763.

11. Bodda C, Tantra M, Mollajew R, Aru-

nachalam JP, Laccone FA, Can K, Ro-

senberger A, Mironov SL, Ehrenreich

H, Mannan AU. Mild overexpression of

Mecp2 in mice causes a higher suscep-

tibility toward seizures. Am J Pathol

2013;183(1):195-210.

12. Rzeszotarska E , Sowinska A , Stypins-

ka B, Walczuk E, Wajda A, Lutkowska A,

Felis-Giemza A, Olesinska M, Puszczewicz

M, Majewski D, Jagodzinski PP, Czerewa-

ty 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.

13. Xie AX, Pan X-Q, Meacham RB, Malykhina

A P. The expression of transcription factors

Mecp2 and CREB Is modulated in inflam-

matory pelvic pain. Front Syst Neurosci

2019;12:69.

14. 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.

15. Branch HzecwgoCMDAD. Chinese Con-

sensus of Herpes Zoster. Chin J Dermatol

2018;51:403–408.

16. Yu S, Wan Y, Wan Q. Chinese expert con-

sensus on diagnosis and treatment of

postherpetic neuralgia. Chin J Pain Med

2016;22:161-167.

17. Wang Y, Liu C, Guo Q-L, Yan J-Q, Zhu X-Y,

Huang C-S, Zou W-Y. Intrathecal 5-azacyti-

dine inhibits global DNA methylation and

methyl-CpG-binding protein 2 expression

and alleviates neuropathic pain in rats fo-

llowing chronic constriction injury. Brain

Res 2011;1418:64-69.

18. 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 develop-

ment and acute inflammation. Dis Model

Mech 2017;10(12):1439-1451.

19. Li C, Jiang S, Liu S-Q, Lykken E, Zhao

L-t, Sevilla J, Zhu B, Li Q-J. MeCP2 en-

forces Foxp3 expression to promote regu-

latory T cells’ resilience to inflammation.

Proc Natl Acad Sci 2014;111(27):E2807-

E2816.

20. 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.

21. Wittrahm R, Takalo M, Marttinen M, Kuu-

lasmaa T, Mäkinen P, Kemppainen S, Mar-

tiskainen 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.

22. Zhang R, Huang M, Cao Z, Qi J, Qiu Z,

Chiang L-Y. MeCP2 plays an analgesic

role in pain transmission through regu-

lating CREB/miR-132 pathway. Mol Pain

2015;11:s12990-015.

23. Zalosnik MI, Fabio MC, Bertoldi ML, Casta-

ñares CN, Degano AL. MeCP2 deficiency exa-

cerbates the neuroinflammatory setting and

autoreactive response during an autoimmune

challenge. Sci Rep 2021;11(1):1-15.

MECP2 in postherpetic neuralgia 91

Vol. 63(1): 81 - 91, 2022

24. Zhao W, Wang Y, Fang Q, Wu J, Gao X, Liu

H, Cao L, An J. Changes in neurotrophic

and inflammatory factors in the cerebrospi-

nal fluid of patients with postherpetic neu-

ralgia. Neurosci Lett 2017;637:108-113.

25. 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.

26. 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.