The concentration of serum neopterin in patients with surgical treatment of spondyloarthrosis complicated byfacet syndrome

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INTRODUCTION

Spondyloarthrosis is manifested by degenerative damage to the intervertebral joints involving cartilage, bones, ligaments, and muscles. A specific symptom of spondyloarthrosis is chronic pain, which intensifies with movement, which is accompanied by limited mobility and unstable morning stiffness [1; 2]. In some cases, lumbar pain is caused by radiculopathy [3]. Pain syndrome associated with damage to the facet joints of the lumbar spine is less known. Its occurrence may be associated with trauma [4; 5] and effusion [6].

Spondyloarthrosis is associated with static–dynamic loads, age-related degenerative–dystrophic processes in osteochondral tissue, and metabolic disorders in the human body. A study described a change in the pool of amino acids in the blood plasma during severe chronic pain syndrome [7]. The study of the serum concentrations of not only nitrogenous compounds related to amino acids, but also metabolites of nucleic acid metabolism, particularly derivatives of purines and pyrimidines, is of particular interest. Neopterin, a derivative of pterins, is one of the metabolites of purine metabolism, intensively studied in recent decades, and synthesized by cells of the monocyte–macrophage series under the influence of interferons [8; 9]. Changes in neopterin concentration are mainly caused by diseases that occur with the activation of cytotoxic immune response, particularly infectious diseases caused by viruses, autoimmune diseases, and tumor processes [10–13].

Previously, we performed a preliminary assessment of the concentrations of neopterin in the blood serum of patients with pain syndrome related to spondyloarthrosis of the lumbar spine before and after treatment [14]. However, the group of patients examined was quite heterogeneous and had various concomitant diseases. Thus, examining a more homogeneous sample with the inclusion of patients with pain syndrome that developed in patients with spondyloarthrosis or spinal cord root entrapment appears appropriate.

This study aimed to analyze the dynamics of changes in serum neopterin concentrations in patients before and after surgical treatment of chronic pain syndrome related with spon­dyloarthrosis-associated facet syndrome.

MATERIALS AND METHODS

This observational, cross-sectional case-control study was performed in compliance with the ethical principles of medical research involving human subjects as set out in the Declaration of Helsinki of the World Health Organization.

The study enrolled 52 patients (male, n = 32; female, n = 20) hospitalized in the neurosurgical department of City Clinical Hospital No. 4. The main group consisted of 26 patients hospitalized for spondyloarthrosis complicated by chronic pain due to facet syndrome. Considering that this group of patients received surgical treatment, the serum concentration of neopterin was determined twice, that is, before surgery during hospitalization and 6 months after surgical treatment. Treatment consisted of high-frequency denervation of the facet joints at the L4–S1 level on both sides.

The inclusion criteria were as follows: (1) pain syndrome, (2) facet syndrome (spondyloarthrosis) confirmed by MRI data, (3) radiculopathy ruled out, (4) ruled out concomitant diseases such as hypertension and diabetes mellitus, in the stage of decompensation, and (5) normal results of a general blood test and a general urinalysis, as well as biochemical blood tests.

The exclusion criteria were as follows: (1) oncological diseases, (2) viral and infectious diseases in the acute phase or <4 weeks after recovery; (3) autoimmune diseases; (4) stage of decompensation of diabetes mellitus, hypertension, and liver and kidney diseases; (5) age <18 years; (6) incapacity; (7) pregnancy; and (8) patient refusal to participate in the study.

The comparison group (n = 26) consisted of patients with pain syndrome caused by to radiculopathy. The control group consisted of 10 patients who underwent periodic examinations, did not present any complaints at the time of the examination, and had normal results of a general analysis of urine, blood, and biochemical blood parameters (glucose and total cholesterol). The groups were comparable in terms of sex ratio and age (p > 0.05). Their comparative characteristics are presented in Table 1.

 

Table 1

Characteristics of the study groups

Characteristics of patients	Main group	Comparison group	Control group
Number of patients examined	26	26	10
Sex ratio (men/women)	15/11	17/9	6/4
Age of subjects, years	39.35 ± 6.56 38 (35; 44)   27–53	39.69 ± 10.9 36.5 (31; 47)   20–68	35.1 ± 5.59 35 (33; 37)   25–46

Note: *― the numerator shows the mean value (M) ± standard deviation (SD), the denominator shows the median (Me) and interquartile range (25 % quartile; 75 % quartile); under the slant line, there are highest and lowest results.

 

Blood samples were collected by vein puncture into vacuum tubes with a coagulation activator. After clot formation, the samples were centrifuged for 15 min at 3000 rpm using an Elekon CLMN-R-10-02 centrifuge. After performing all necessary tests, the remaining serum samples were separated and aliquoted into microtubes (Eppendorf – 0.7 mL) and stored at −20 °C until further studies.

The concentration of neopterin was determined by enzyme-linked immunosorbent assay (ELISA) using the Neopterin ELISA test system (Cat. No. 59321; lot ENO230, IBL, Germany), with manufactured-reported sensitivity of at least 0.7 nmol/L. The optical density of the samples was measured on a StatFax 3200 vertical photometer (Awareness, USA). Data accuracy was monitored based on the measurement results of two control samples that were part of the test systems. The neopterin content in control sample 1 was 5.48 nmol/L, with an acceptable range of results of 3.5–8.1 nmol/l, and in sample 2, it was 23.34 nmol/L with an acceptable range of 13.6–28.2 nmol/L.

For statistical processing of the study results, Statistica version 7 (StatSoft Inc., USA) was used. For the results obtained in each group, arithmetic mean (M) and standard deviation (SD) were calculated for a normal distribution of the trait and Me (median) and interquartile range (25–75th percentile) for a nonnormal distribution. To assess the distribution of results within the sample, the Shapiro–Wilk test was used. Therefore, for further calculations, nonparametric statistics methods were used (Table 2).

 

Table 2

Concentration of neopetrin (nmol/L) in the study groups

Characteristics of patients	Main group		Comparison group	Control group
	before surgery	after surgery
Number of patients examined, n	26	26	26	10
Neopterin concentration, nmol/L	9.03 ± 1.39 8.87 (7.93; 9.7)   8.87–13.7	7.93 ± 2.36 7.64 (6.47; 9.68)   3.19–11.91	10.31 ± 2.02 9.82 (8.71; 11.87)   8.15–14.89	8.21 ± 0.85 8.21 (7.36; 8.71)   7.07–9.72
Shapiro–Wilk W test	0.88573 (р = 0.00762)	0.96754 (р = 0.56065)	0.88409 (р = 0.00703)	0.94675 (р = 0.63022)
Kruskal–Wallis H test	H test = 12.86557; р = 0.0016 Median test: (р1,3) = 0.338734; (р1,2) = 0.049955; (р2,3) = 0.02256
Wilcoxon test	р = 0.049029		-	-

Note: * ― the numerator shows the mean value (M) ± standard deviation (SD), and the denominator shows the median (Me) and interquartile range (25 % quartile; 75 % quartile); under the slant line, there are highest and lowest results.

 

To compare neopterin content, the Wilcoxon and Kruskal–Wallis tests were used in related and unrelated groups, respectively (n > 3). The median test was used to compare further results between individual unrelated groups. A statistical significance level value ≤0.05 was taken as the maximum permissible probability of a type 1 error (p).

RESULTS AND DISCUSSION

Descriptive statistics characterizing the concentrations of neopterin in the studied groups are presented in Table 2. Statistically significant differences in the serum levels of neopterin were revealed between the studied groups (Fig. 1).

 

Fig. 1. Neopterin concentration (nmol/L) in the blood serum of the studied groups

 

Before treatment, when comparing neopterin levels between patients, a statistically significant increase (p < 0.05) was revealed in the comparison group in patients with radicular pain syndrome. The median serum level of neopterin in the comparison group was 1.088 times higher than that in the main group (p = 0.049955) and 1.197 times higher than the data in the control group (p = 0.02256) (Table 2). Thus, statistically significant between-group differences were detected.

After surgical treatment, the serum concentration of neopterin in the main group with facet syndrome decreased statistically significantly (Wilcoxon test, p = 0.049029) and approached the indicators of the control group (Mann – Whitney U test, 114.5; p = 0. 589812) (Fig. 2). 

 

Fig. 2. Neopterin concentration (nmol/L) in the blood serum of patients of the main group after surgical treatment and control group

 

The higher concentration of neopterin in the blood serum of patients with pain syndrome caused by radiculopathy can be explained by the presence of neurogenic inflammation, which is accompanied by a greater release of proinflammatory factors that activate the antinociceptive purinergic system, in comparison with pain syndrome that develops in patients with spondyloarthrosis of the lumbar spine with facet syndrome development [15; 16]. In our opinion, this mechanism can lead to an increase in the serum concentration of neopterin [17; 18]. The prognostic value of studying the postoperative neopterin was identified in the authors’ works when predicting postcholecystectomy syndrome¹ and other diseases [19].

Data are in poor correspondence with the preliminary results of the examination of patients who received high-frequency denervation of the facet joints [14]. However, with a more stringent selection of groups and an increase in the follow-up period to 3 months, this study revealed a statistically significant decrease in the concentration of neopterin in the blood serum.

An increase in the serum concentration of neopterin in the presence of diseases may be significant in the somatization of symptoms of diseases of internal organs [20]. In general, more studies are needed to clarify the role and pathogenesis of the effects of pain on the metabolism of tissues and organs.

CONCLUSIONS

1. The initial concentration of neopterin in spondyloarthrosis with the emergence of acute pain syndrome (facet syndrome) is not statistically significantly different from the examination results of the control group (p = 0.338734).
2. An effective treatment of pain syndrome caused by the compression of nerves in the area of the facet joints in spondyloarthrosis is accompanied by a statistically significant decrease not only in pain but also in the serum concentration of neopterin (p = 0.049029).
3. Further research is necessary to clarify the effect of pain on metabolic processes.

 

Funding. The study had no external funding.

Conflict of interest. The authors declare no conflict of interest.

Author contributions: A.Yu. Pronin collected the patient data, typed material, wrote the text, and performed statistical data processing (50 %). Yu.V. Karakulova created the idea of the article and the study plan, edited, and approval of the final text of the article (35 %). D.Yu. Sosnin performed laboratory tests (15 %).

 

¹ O.V. Boyko, Yu.V. Kondrashova, A.V. Zhurikhin, and V.I. Boyko, RU patent No. 2498303.

About the authors

Artur Yu. Pronin

E.A. Vagner Perm State Medical University; City Clinical Hospital № 4

Email: proninartur@icloud.com
ORCID iD: 0009-0003-9555-8014

Candidate for a Degree of the Department of Neurology and Medical Genetics, Neurosurgeon

Russian Federation, Perm; Perm

Yuliya V. Karakulova

E.A. Vagner Perm State Medical University; City Clinical Hospital № 4

Email: julia.karakulova@mail.ru
ORCID iD: 0000-0002-7536-2060
SPIN-code: 5066-6556

MD, PhD, Professor, Head of the Department of Neurology and Medical Genetics

Russian Federation, Perm; Perm

Dmitriy Yu. Sosnin

E.A. Vagner Perm State Medical University

Author for correspondence.
Email: sosnin_dm@mail.ru
ORCID iD: 0000-0002-1232-8826
SPIN-code: 4204-6796

MD, PhD, Professor of the Department of Faculty Therapy №2, Occupational Pathology and Clinical Laboratory Diagnostics

Russian Federation, Perm

References

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