Maslova I. Personalized treatment of patients with back pain taking into account clinical and genetic correlations.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0420U101640

Applicant for

Specialization

  • 14.01.15 - Нервові хвороби

24-09-2020

Specialized Academic Board

Д 26.613.01

Shupyk National Medical Academy of Postgraduate Education

Essay

The thesis is based on the clinical, neurological, psychological, immunological and genetic studies of 138 patients with acute non-specific dorsalgia of different localizations, that have been treated with nonsteroidal anti-inflammatory drugs for 10 days and then observed for 90 days. We use VAS (Visual Analog Scale) and DN-4 (Douleur Neuropathique en 4 Questions) to estimate the pain syndrome, BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory) to estimate the psycho-emotional state, SF-36 (The Short Form-36) to estimate patients` quality of life. We used enzyme-linked immunosorbent assay (ELISA) to determine immunological markers of inflammation - levels of pro-inflammatory (interleukin -1β, IL -1β, interleukin -6, IL-6) and anti-inflammatory cytokines (interleukin -10, IL-6) and polymerase chain reaction (PCR) of whole venous blood leukocyte DNA to determine the CYP2C9 genetic polymorphism. Factors that influence the characteristics of the pain syndrome in acute dorsalgia during the course of NSAID treatment, as well as the risks of pain chronization were identified. The influence of pain localization and pain characteristics on various aspects of patient’s quality of life, according to the SF-36 was demonstrated– the level of physical health decreased more in cases of lumbalgia and lumbosciatica, and the level of mental health decreased more the more cranial pain localization was - cervicalgia, cervicocranialgia. The correlation between the pain dynamics and the level of pro-inflammatory (interleukin-1, interleukin-6) and anti-inflammatory (interleukin - 10) cytokines was demonstrated, as well as the correlation between long-term prognosis of dorsalgia and the dynamics of blood cytokine levels during the first 10 days of NSAID treatment. The frequency of mutations to impaired CYP2C9 metabolism in the population of the south-eastern region of Ukraine was established - these people have a fast-acting pattern due to the slow metabolism of NSAIDs. The superior analgesic effect of celecoxib in patients who carried heterozygous CYP2C9 (Arg144Cys), CYP2C9 (IIe369Leu) alleles was demonstrated. Therefore, in these cases celecoxib had greater potential to provoke adverse effects, especially in patients with pre-existing gastric pathology, e.g. the history of gastric bleeding, or in cases of concomitant use of other medicines that are metabolized by the same enzyme systems. A new personalized approach to the acute dorsalgia diagnostics and treatment was developed, which provided better prognosis, more effective and safer treatment of patients and reduced the risk of pain chronization.

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