EXPERIMENTAL STUDY OF NEUROPATHIC PAIN TREATMENT UNDER MULTIPLE SCLEROSIS MODELING

Nefodov O. O., Miasoied Yu. P., Solomenko M. V., Velykorodna-Tanasiichuk O. V., Baklunov V. V., Adehova L. Ia., Kuznetsova O. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Treatment of patients with neuropathic pain in the case of multiple concomitant diseases – a complex multidisciplinary process. According to modern recommendations, gabapentinoids (gabapentinoids and pregabalin), tricyclic antidepressants and serotonin reuptake inhibitors and norepinephrine are preparations of the first line in therapy in the case of neuropathic pain. Purpose of work: By comparative system, analysis and the use of complex methodological approaches to experimentally substantiate ways of pharmacological correction of pain syndrome and medical brain protection under the experimental equivalent of scattered sclerosis. Object and methods. To study PC we used an experimental model with autoimmune mechanisms of inflammatory demyelinization – a model of experimental allergic encephalomyelitis. Tactile alodium was studied in the modification of the philament test Von Frey by registration of pressure, in which the animals were drained by the left back paw, avoiding the effects of growing stimulus. The assessment of manifestations of chemical hyperalgia was carried out using a formalin test. The study of manifestations of thermal hyperalgia was performed using a hot plate test. Results. For the therapy of neuropathic pain syndrome with multiple sclerosis, amitriptylin, lamotrigin, carbamazepine, gabapentin, topiramate is used, although large-scale evidence-based research effects of these drugs was not carried out. Taking into account the indicated, we considered appropriate to conduct a comparative pharmacological analysis of the influence of anticonvulsants (carbamazepine, topiramate, sodium voliproat, gabapentin and pregabalin) on manifestations of neuropathic pain syndrome in conditions of experimental allergic encephalomyelitis. It is shown that after the course administration of anticonvulsants, the total amount of fragments caused by an injection of 0.5% formalin solution in the back surface of the EAE-associated rats was smaller than in the control group. Thus, the number of responses of the early and late phase under the influence of gabapentin and pregabalin is statistically significantly reduced by 46% (p<0.05) and 43% (p<0.05), respectively. In this case, the weakening of chemical hyperalgesia after the administration of carbamazepine (18%, p>0,05), topipamate (29%, p>0,05) and sodium of valproate (24%, p>0,05), was the nature of a moderate tendency. The ability to reduce the severity of tactile alodium decreased in a number of amitriptyline (60%, p<0.05)> trazodone (40%, p <0.05) >> fluoxetin (18%, p>0,05) ≈ paroxetine (14%, p>0.05). Conclusions. Course use of carbamazepine, topiramate, sodium valproate, gabapentin and pregabalin under the conditions of EAE-induced neuropathic pain syndrome causes normalization of tactile and pain sensitivity of varying degrees of severity. The ability to weaken the manifestations of neuropathic pain syndrome under the conditions of experimental equivalent of RS decreases in a number of gabapentin ≥ Pregabalin> sodium valproate ≥ Topiramate> Carbamazepine. Course application of amitriptyline and trasodone, but not paroxetine or fluoxetin under conditions of EAE causes normalization of tactile and pain sensitivity of varying degrees of severity. The ability to weaken the manifestations of neuropathic pain syndrome in the conditions of experimental allergic encephalomyelitis decreases in a series of amitriptyline> trazodone >> fluoxetine ≈ paroxetine.

experimental allergic encephalomyelitis, multiple sclerosis, neuropathic pain, anesthesia, anticonvulsants, antidepressants.

1. Cheng Y-C, Snavely A, Barrett LB, Xuefei Z, Crystal H, Devlin JF, et al. Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons. Cell Rep. 2021;36(10):109666.
2. Nefodov O, Dychko Y, Zhytnii M, Chyrkin V. Experimental study of pharmacotherapy of neurological diseases for multiple sclerosis. Modern Science – Moderní věda. 2021;5:137-142.
3. Kim JA, Bosma RL, Hemington KS, Rogachov A, Osborne NR, Cheng JC, et al. Cross-network coupling of neural oscillations in the dynamic pain connectome reflects chronic neuropathic pain in multiple sclerosis. Neuroimage Clin. 2020;26:102230.
4. Sedal L, Winkel A, Laing J, Law LY, McDonald E. Current concepts in multiple sclerosis therapy. Degener Neurol Neuromuscul Dis. 2017;7:109-125.
5. Xu Z, Wu J, Zheng J. Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors. Int. Immunopharmacol. 2015;25(2):528-537.
6. Burlaka BS, Belenichev IF, Nosach SG, Nefedov AA. Morpho-functional parameters of neurons in the sensorimotor cortex and neuroapoptosis under conditions of an induced experimental allergic encephalomyelitis in rats and a course of intranasal gel administration containing N-phrnylacetyl-L-prolylglycine (noopept). Journal of Education, Health and Sport. 2021;11(1):191-201.
7. Belenichev IF, Gorchakova NO, Bukhtiyarova NV, Samura IB, Savchenko NV, Nefodov OO, et al. Modulation of HSP70-dependent mechanisms of endogenous neuroprotection with selenium derivatives under conditions of ischemic-type acute cerebrovascular accident modeling. Pedagogy and Psychology of Sport. 2020;6(4):99-108.
8. Reynolds ES. The use of lead citrate at high ph an electronopaque stain in electron microscopy. J. Cell Biol. 1963;17:208-212.
9. Burlaka BS, Belenichev IF, Nefedov OO, Alieva OG, Bukhtiyarova NV. Neuroprotective properties of N-phenylacetyl-L-prolylglycine tthyl ester nasal gel in an experimental model of multiple sclerosis equivalent. Medychni perspektyvy. 2020;4:31-38.
10. May ES, Gil Ávila C, Ta Dinh S, Heitmann H, Hohn VD, Nickel MM, et al. Dynamics of brain function in patients with chronic pain assessed by microstate analysis of resting-state electroencephalography. Pain. 2021;162(12):2894-2908.
11. Pérez-Hernández C, Blasco A, Gándara A, Mañas A, Rodríguez-López MJ, Martínez V, et al. Prevalence and characterization of breakthrough pain in patients with cancer in Spain: the CARPE-DIO study. Carmen Montoto Sci. 2019;9:17701.
12. Nefodov OO, Mamchur VY. Eksperimentalniy alergichniy entsefalomielit: osoblivosti znebolyuyuchoyi terapiyi ta mistse antikonvulsantiv u yakosti analgetikiv. Medichni perspektivi. 2015;4:4-10. [in Ukrainian].
13. Nefedov AA, Mamchur VI. Otsenka antinotsitseptivnogo potentsiala antidepressantov v terapii nevropaticheskoy boli, indutsirovannoy eksperimentalnyim allergicheskim entsefalomielitom. Bukovynskyi medychnyi visnyk. 2016;1(77):94-98. [in Russian].
14. Nefedov AA. Vozmozhnosti farmakologicheskoy korrektsii bolevogo sindroma pri rasseyannom skleroze. Bukovynskyi medychnyi visnyk. 2015;1(73):232-236. [in Russian].
15. Nefodov OO, Miasoied YuP, Solomenko MV, Velykorodna-Tanasiichuk OV, Baklunov VV, Adehova LIa, et al. Farmakolohiya antynotsytseptsiyi v umovakh eksperymentalʹnoho ekvivalenta rozsiyanoho sklerozu. Visnyk problem biolohii i medytsyny. 2021;3(161):131-136. [in Ukrainian].
16. Zapadnyuk IP, Zapadnyuk VI, Zahariya EA. Laboratornye zhivotnye. Razvedenie, soderzhanie, ispolzovanie v eksperimente. Kyiv; 1983. 383 s. [in Russian].
17. Kozhem’yakin YuM, Hromov OS, Filonenko MA. Naukovo-praktichni rekomendatsiyi z utrimannya laboratornih tvarin ta robot i z nimi. Kyiv; 2002.155 s. [in Russian].
18. Davydova GS, Markov DA. Voprosy napravlennogo modelirovaniya allergicheskogo encefalomielita. Demieliniziruyushie zabolevaniya nervnoj sistemy v eksperimente i klinike; 1975; Minsk. Minsk: «Nauka i tehnika»; 1975. s. 24-33. [in Russian].
19. Davydova GS. Primenenie ayuvanta s razlichnym kolichestvom BCZh dlya vosproizvedeniya EAE u krys. Ostryj encefalomielit v eksperimente i klinike. 1969; Minsk. Minsk: «Nauka i tehnika»; 1969. s. 58-63. [in Russian].
20. Davydova GS, Markov DS. Hronicheskij eksperimentalnyj allergicheskij encefalomielita morskih svinok. Demieliniziruyushie zabolevaniya nervnoj sistemy v eksperimente i klinike. 1970; Minsk. Minsk: «Nauka i tehnika»; 1970. s. 193-206. [in Russian].
21. Chaplan SR, Bach FW, Pogrel JW. Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods. 1994;53(1):55-63.
22. Shibata M, Ohkubo T., Takahashi H. Modified formalin test: characteristic biphasic pain response. Pain. 1989;38:347-352.
23. Hunskaar S, Berge OG, Hole K. A modified hot-plate test sensitive to mild analgesics. Behavioural Brain Res. 1986;21:101-108.
24. Nefedov A, Mamchur V. Pharmacological aspects of the use of anticonvulsants as a means of therapy of neuropathic pain syndrome in experimental allergic encephalomyelitis. Modern Science – Moderní věda. 2015;5:118-125.
25. Nefedov AA, Mamchur VI. Pharmacological Correction of Neurological Disorders in Case of Multiple Sclerosis. Galician Medical J. 2015;22(4):39-41.

«Bulletin of problems biology and medicine» Issue 4 (162), 2021 year, 141-148 pages, index UDK 616.832-004.2-092.9:615.212.3

10.29254/2077-4214-2021-4-162-141-148