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Analysis of the association of the PRDM12 gene with pain sensitivity in individuals with psychoactive substance dependence

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Abstract

Early diagnosis of susceptibility to the use of psychoactive substances (PAS) and the formation of addiction is a pressing problem of addictology. The development of addiction to psychoactive substances involved a reward system, which also plays a key role in the modulation of nociception. PRDM12, associated with innate insensitivity to pain, is involved in neurogenesis and affects the properties of nerve cells.

Objective: to conduct a comparative assessment of pain sensitivity in people with mental and behavioral disorders caused by the use of psychoactive substances in healthy individuals and in the group of people with episodic use of PAS depending on the rs10121864 genotype of the PRDM12 gene.

Patients and methods. Surveyed 103 people with addiction to PAS (F1x.2), 114 conditionally healthy individuals, 36 people, occasionally using psychoactive substances (risk group). Thresholds of pain sensitivity and tolerability of pain were determined by the method of tensoalgometry; using a visual analogue scale to determine the subjective assessment of pain thresholds. Genotyping was performed on the rs10121864 polymorphism of the PRDM12 gene.

Results and discussion. The distribution of rs10121864 genotypes of the PRDM12 gene in the comparison groups was statistically significantly different. The calculation of the odds ratio showed that among individuals who occasionally use PAS, the risk of developing dependence on PAS is several times higher among carriers of the mutant A allele (OR=2.52; 95% Cl=1.42–4.50) rs10121864 and its homozygous AA genotype (OR=6.66; 95% Cl=1.50–29.54) than carriers of alternative genotypes. An association rs10121864 PRDM12 was also identified with an indicator of the subjective assessment of pain sensitivity among people with addiction to PAS. Thus, in the carriers of the mutant allele A (genotypes AA and AG), this indicator was significantly lower than in carriers of the GG genotype.

Conclusion Associations of allele A and the AA rs10121864 genotype of the PRDM12 gene are identified with the risk of developing dependence on PAS and with the indicator of the subjective perception of the upper pain threshold.

About the Authors

E. G. Poltavskaya
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation
Tomsk


D. N. Savochkina
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation
Tomsk


References

1. Смирнов АВ. Предрасположенность к аддиктивному поведению в структуре интегральной индивидуальности. Психопедагогика в правоохранительных органах. 2010;2(41):44–49.

2. Фурманов ИА, Сизанов АН, Хриптович ВА. Профилактика нарушений поведения в учреждениях образования: Учебно-методическое пособие. Минск: РИВШ; 2011. 250 с.

3. Внуков ВВ, Черникова ИВ, Милютина НП и др. Молекулярные и клеточные механизмы опийной наркомании. Журнал фундаментальной медицины и биологии. 2013;3:4–12.

4. Гуров ДЮ, Туманов ВП, Смирнов АВ и др. Морфологические изменения нейронов супраоптических ядер гипоталамуса крыс, предрасположенных к алкогольной зависимости. Современные проблемы науки и образования. 2019;2:163.

5. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35:217–38.

6. Clarke TK, Krause K, Li T, Schumann G. An association of prodynorphin polymorphisms and opioid dependence in females in a Chinese population. Addict Biol. 2009;14:366–70.

7. Koob GF. Neurocircuitry of alcohol addiction: synthesis from animal models. Handb Clin Neurol. 2014;125:33–54.

8. Belin D, Everitt BJ. Cocaine seeking habits depend upon dopaminedependent serial connectivity linking the ventral with the dorsal striatum. Neuron. 2008;57:432–41.

9. Wise RA. The brain and reward. In: Liebman JM, Cooper SJ, editors. The neuropharmacological basis of reward. Oxford, UK: Clarendon; 1989. p. 377–424.

10. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8:1481–9.

11. Sesack SR, Grace AA. Cortico-Basal Ganglia reward network: microcircuitry. Neuropsychopharmacology. 2010;35:27–47

12. Bailey KP. The brain's rewarding system & addiction. J. Psychosoc. Nurs. Ment. Health Serv. 2004;6(42):14–18.

13. Лелевич ВВ, Курбат МН, Лелевич СВ. Нейромедиаторные механизмы опиатной наркомании (обзор литературы). Журнал ГрГМУ. 2006;3:12-15.

14. Cohen JY, Haesler S, Vong L, Lowell BB, Uchida N. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature. 2012;482:85–88.

15. Mitsi V, Zachariou V. Modulation of pain, nociception, and analgesia by the brain reward center. Neuroscience. 2016;3:81–92.

16. Nevidimova TI, Batukhtina EI, Vetlugina TP et al. Association of Cytokine Production with Hormone Level and Sensory Responses during the Formation of Psychoactive Drug Addiction in Men. Bull Exp Biol Med. 2015;159(6):768–71.

17. Chen YC, Auer-Grumbach M, Matsukawa S et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat Gene. 2015;47:803–808.

18. Hohenauer T, Moore AW. The Prdm family: expanding roles in stem cells and development. Development. 2012;139(13):2267–2282.

19. Cortes D, Holt R, de Knegt VE. Hormonal aspects of the pathogenesis and treatment of cryptorchidism. Eur. J. Pediatr. Surg. 2016;26:409–417.

20. Shirane K, Kurimoto K, Yabuta Y, Yamaji M, Satoh J, Ito S, Watanabe A, Hayashi K, Saitou M, Sasaki H. Global landscape and regulatory principles of DNA methylation reprogramming for germ cell specification by mouse pluripotent stem cells. Dev. Cell. 2016;39:87–103.

21. Kobayashi T, Zhang H, Tang WWC et al. Principles of early human development and germ cell program from conserved model systems. Nature. 2017;546:416–420.

22. Dickinson ME, Flenniken AM, Ji X et al. High-throuput discovery of novel developmental phenotypes. Nature. 2016;537:508–514.

23. Smagulova F, Brick K, Pu Y et al. The evolutionary turnover of recombination hot spots contributes to speciation in mice. Genes Dev. 2016;30:266–280.

24. Kinameri E, Inoue T, Aruga J, Imayoshi I, Kageyama R, Shimogori T, Moore AW. Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis. PLoS One. 2008;3(12).e3859.

25. Saitou M, Kagiwada S, Kurimoto K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development. 2012;139:15–31.

26. Yang CM, Shinkai Y. Prdm12 is induced by retinoic acid and exhibits antiproliferative properties through the cell cycle modulation of P19 embryonic carcinoma cells. Cell. Struct. Funct. 2013;38:197–206.

27. Nagy V, Cole T, Van Campenhout C et al. The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception. Cell Cycle. 2015;14:1799–1808.

28. Meehan TF, Conte N, West DB et al. Disease model discovery from 3328 gene knockouts by the international mouse phenotyping consortium. Nat. Genet. 2017;49:1231–1238.

29. Бохан НА, Мандель АИ, Иванова СА и др. Старые и новые проблемы наркологии в контексте междисциплинарных исследований. Вопросы наркологии. 2017;1:26–62.

30. Fedorenko OY, Golimbet VE, Ivanova SА et al. Opening up new horizons for psychiatric genetics in the Russian Federation: moving toward a national consortium. Mol Psychiatry. 2019;24(8):1099–1111.

31. Невидимова ТИ, Бохан НА, Коконова ДН. Способ количественной оценки индивидуальных болевых порогов. Патент на изобретение № 2342063. Зарегистрировано в Государственном реестре изобретений 27.12.2008 г.

32. Савочкина ДН, Полтавская ЕГ. Оценка психофизиологических характеристик и полиморфизма гена SCN9A при формировании аддиктивного поведения. Сибирский вестник психиатрии и наркологии. 2018;4(101):11–15.

33. Kelley AE, Berridge Kent C. The neuroscience of natural rewards: Relevance to addictive drugs. J Neurosci. 2002;22:3306–3311.

34. Blum K, Gold MS. Reward circuitry dopaminergic activation regulates food and drug craving behavior. Curr Pharm Des. 2011;17:1158–1225.

35. Miller NS, Gold MS. Opiate prescription medication dependence and pain perceptions. J Addict Dis. 2007;1(26):65–71.

36. Aniskin DB, Fink E, Prosser J, Cohen LJ, Boda N, Steinfeld M, Galynker II. The effect of pain on stroop performance in patients with opiate dependence in sustained remission. J Addict Med. 2011;1(5):50–56.

37. Compton P, Canamar CP, Hillhouse M et al. Hyperalgesia in heroin dependent patients and the effects of opioid substitution therapy. J Pain. 2012;13(4):401–9.

38. Woller SA, Moreno GL, Hart N et al. Analgesia or addiction?: implications for morphine use after spinal cord injury. J Neurotrauma 2012;29(8):1650–62.


For citation:


Poltavskaya E.G., Savochkina D.N. Analysis of the association of the PRDM12 gene with pain sensitivity in individuals with psychoactive substance dependence. Neurology, Neuropsychiatry, Psychosomatics. 0;. (In Russ.)

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