ABSTRACT

Chronic back pain (CBP) is a significant medical and social problem due to the complex interaction of peripheral and central mechanisms. This article is devoted to the analysis of the role of central sensitization and disinhibition in the pathogenesis of CPS, as well as to the rationale for the use of myorelaxants in the complex therapy of this condition. Central sensitization, characterized by increased excitability of neurons of the central nervous system, plays a key role in chronicity of pain syndrome. It results from prolonged nociceptive impulses, leading to changes in synaptic transmission and neuronal plasticity. Disinhibition, a decrease in the activity of inhibitory neuronal circuits, exacerbates central sensitization, contributing to increased pain perception and pain spread beyond the original focus. Myorelaxants, acting at different levels of the nervous system, help to reduce local muscle spasm, decrease pain impulsation and attenuate central sensitization. However, the efficacy and safety of different myorelaxants in CPS vary. The combination of mirtazapine (an antidepressant with analgesic properties) and tizanidine (a centrally acting myorelaxant) represents a promising approach to the complex effect on chronic pain mechanisms, modulating both central sensitization and disinhibition.

KEYWORDS: Chronic back pain, central sensitization, disinhibition, nociception, neuroplasticity, tizanidine, mirtazapine, myorelaxants

For citation: Rachin A.P., Amelin A.V., Karpov S.M., Sharov M.N., Parsamyan R.R., Rachin S.A., Prokofieva Y.S. The Role of Central Sensitization and Disinhibition in the Maintenance of Chronic Back Pain: Focus on Myorelaxants. A Review. Comorbidity Neurology. 2025; 2 (1): 74-82. https://doi.org/10.62505/3034-185x-2025-2-1-74-82

*For correspondence: Andrei Rachin, M.D., Professor, National Association of Experts in Comorbid Neurology, Moscow, Russia, e-mail: 7851377@gmail.com

REFERENCES

1.Амелин А.В., Ахмадеева Л.Р., Ачкасов Е.В., Баранцевич Е.Р., Барулин А.Е., Бахтадзе М.А., Белова А.Н., Бельская Г.Н., Быченко В.Г., Васильев С.А., Головачева В.А., Давыдов О.С., Евзиков Г.Ю., Загорулько О.И., Исагулян Э.Д., Исайкин А.И., Искра Д.А., Калинский П.П., Каратеев А.Е., Кукушкин М.Л. и др. Диагностика и лечение скелетно-мышечных (неспецифических) болей в нижней части спины. Клинические рекомендации. М., 2021 (In Russ.)

2.Apkarian A.V., Baliki M., Geha P.Y. Towards a theory of chronic pain. Progress in Neurobiology. 2009; 87 (3): 81-97. https://doi.org/10.1016/j.pneurobio.2008.09.018

3.Woolf C.J. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011; 152 (Suppl 3): S2-S15. https://doi.org/10.1016/j.pain.2010.09.030

4.Latremoliere A., Woolf C.J. Central sensitization: a generator of pain hypersensitivity by central mechanisms. The Journal of Pain. 2009; 10 (9): 895-926. https://doi.org/10.1016/j.jpain.2009.06.012

5.Sanzarello I., Merlini L., Rosa M.A., et al. Central sensitization in chronic low back pain: a narrative review. J Back Musculoskelet Rehabil. 2016; 29 (4): 625-633. https://doi.org/10.3233/BMR-160685

6.Sandkühler J. Models and mechanisms of hyperalgesia and allodynia. Physiological Reviews. 2009; 89 (3): 707-758. https://doi.org/10.1152/physrev.00025.2008

7.Julien N., Goffaux P., Arsenault P., Marchand S. Widespread pain in chronic back pain associated with enhanced processing of noxious stimuli in the central nervous system. Pain. 2005; 114 (1-2): 192-200. https://doi.org/10.1016/j.pain.2004.12.032

8.Staud R., Rodriguez M.E., Price D.D. Evidence for abnormal pain processing in patients with chronic low back pain. Pain. 2007; 129 (3): 256-264

9.Ossipov M.H., Morimura Y., Porreca F. Descending inhibitory and facilitatory systems: mediating mechanisms and clinical implications. Pain. 2005; 113 (1-2): 1-5

10.Scholz J., Woolf C.J. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007; 10 (11): 1361–1368. https://doi.org/10.1038/nn1992

11.Davydov O.S. The peripheral and central mechanisms of transition of acute to chronic pain and the possible role of cyclooxygenase-2 inhibition in the prevention of pain syndrome chronization. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2016; 8 (2): 10–16. https://doi.org/10.14412/2074-2711-2016-2-10-16 (In Russ.)

12. Danilov A.B. Pain of a mixed type. Pathophysiological mechanisms are important for clinical practice. Approaches to the diagnosis and treatment of mixed types of pain syndromes. Russian Medical Journal. 2014; 10. (In Russ.)

13.Nijs J., Van Houdenhove B., Oostendorp R.A.B., Hendrix T., Meeus M., Roussel N.A., Paul van Wilgen C. Recognition of central sensitization in patients with musculoskeletal pain: Application of a symptom inventory. Manual Therapy. 2010; 15 (2): 135-141. https://doi.org/10.1016/j.math.2009.12.001

14.Meeus M., Nijs J., Van Oosterwijck J., Van Gestel S., Calders P. Pain assessment in patients with chronic musculoskeletal pain: which methods to use? Clinical Rheumatology. 2011; 30 (1): 39-46

15.Smart K.M., Blake C., Staines I., Doody C. The Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS): psychometric properties and associations with somatosensory abnormalities in patients with chronic musculoskeletal pain. BMC Musculoskeletal Disorders. 2012; 13 (1): 1-11

16.Imamura M., Chen J., Matsubayashi S.R., et al. Changes in pressure pain threshold in patients with chronic nonspecific low back pain. Spine. 2013; 38 (24): 2098–2107.  https://doi.org/10.1097/ 01.brs.0000435027.50317.d7

17.Rachin A.P., Sharov M.N., Rachin S.A., Prokofieva Y.S., Parsamyan R.R. Chronic (Non-Oncologic and Oncologic) Pain: a Rational Approach to Conservative Therapy. Comorbidity Neurology. 2024; 1 (2): 28–39. https://doi.org/10.62505/3034-185x-2024-1-2-28-39 (In Russ.)

18.Pilipovich A.A., Danilov A.B. Differentiated approach to pain therapy: the role of nonsteroidal anti-inflammatory drugs. Russian Medical Journal. 2013; 18. (In Russ.)

19.Zhu L-L., Wang Y-H., Zhou Q. Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations. Journal of Pain Research. 2024; 17: 1257-1271. https://doi.org/10.2147/JPR.S461032

20. Barantsevich E.R., Zhivolupov S.A., Samartsev I.N. Priority directions in the formation of disease-modifying complex therapy of chronic pain syndromes in neurology. Russian Medical Journal. 2017; 9: 642-647 (In Russ.)

21.Danilov A.B., Yakupov E.Z., Sivolap Yu.P., Kozlov I.G., Shirokov V.A. Multivalent effect on chronic back pain: results of randomized clinical trials of Dorsumio. Russian Journal of Pain. 2024; 22 (3): 63‑73. https://doi.org/10.17116/pain20242203163 (In Russ.)

22.Goncharov A.S., Grigoriev A.V., Globenko A.A., Goncharov I.S., Muratov K.A., Yaroshenko D.V., Sidorova A.A., Kapashin A.V., Kovchan O.V, Bashkatova A.I., Pasko M.A. Pharmacokinetic parameters, safety and drug-drug interactions of mirtazapine and tizanidine, combined in the new original drug Dorsumio. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2023; 15 (4): 80–88. https://doi.org/10.14412/2074-2711-2023-4-80-88 (In Russ.)

23.  Общая характеристика лекарственного препарата Дорсумио 

ADDITIONAL INFORMATION

Andrei P. Rachin, Dr. Sci. (Med.), Professor, President of the National Association of Experts in Comorbid Neurology, Moscow, Russia. E-mail: 7851377@gmail.com. ORCID: https://orcid.org/0000-0003-4266-0050

Alexander V. Amelin, Dr. Sci. (Med.), Professor, Professor of the Department of Neurology with Clinic, Head of the Headache Diagnosis and Treatment Centre, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia. E-mail: avamelin@mail.ru. ORCID:  https://orcid.org/0000-0001-6437-232X

Sergey M. Karpov, Dr. Sci. (Med.), Professor, Head of the Department of Neurology, Neurosurgery and Medical Genetics Stavropol State Medical University, Stavropol, Russia. E-mail: karpov25@rambler.ru. ORCID: https://orcid.org/0000-0003-1472-6024

Mikhail N. Sharov, Dr. Sci. (Med.), Professor, Department of Therapy, Clinical Pharmacology and Emergency Medicine, Moscow, Russia. E-mail: 6112286@mail.ru. ORCID: https://orcid.org/0000-0001-9634-346X

Ruzanna R. Parsamyan, Cand. Sci. (Med.), Associate Professor of the Department of Neurology named after K.N. Tretyakova, Senior Researcher at the Department of Basic Research in Neurocardiology, Research Institute of Cardiology, Saratov State Medical University, Head of Clinic Pain, Saratov. Russia. E-mail: kvl.prr@mail.ru. ORCID: https://orcid.org/0000-0002-6509-5958

Sergey A. Rachin, Executive Director, National Association of Experts in Comorbid Neurology, Moscow, Russia. E-mail: Rachin.sergei@gmail.com. ORCID: https://orcid.org/0000-0001-9771-4621

Yulia S. Prokofieva, postgraduate student of the Department of Nervous Diseases, Faculty of Dentistry, Russian University of Medicine, Moscow, Russia. E-mail: pryulek@yandex.ru. ORCID: https://orcid.org/0000-0003-4454-7174

Author contributions. All authors confirm the compliance of their authorship, according to international ICMJE criteria (all authors made a significant contribution to the development of the concept, research and preparation of the article, read and approved the final version before publication). Rachin S.A., Prokofieva Yu.S., Parsamyan R.R. – formal analysis, writing – original draft; Rachin S.A., Amelin A.V., Karpov S.M., Sharov M.N.– writing – review & editing.

Funding. This study was supported by any external sources of funding.

Disclosure. Rachin A.P. – editor-in-chief of the journal «Comorbidity Neurology». Sharov M.N., Amelin A.V. – Members of the editorial council of the journal «Comorbidity Neurology». Karpov S.M. – member of the editorial board of the journal «Comorbidity Neurology». Other authors declare apparent or potential conflicts of interest related to the publication of this article.

The content is available under the Creative Commons Attribution 4.0 License.

©2025. Andrei P. Rachin, Alexander V.Amelin, Sergei M. Karpov et al.