ARTICLE PDF (Українська)


inflammatory mediators
pain receptors

How to Cite

Gorpynchenko, I. I., Nurimanov, K. R., & Nedogonova , O. A. (2023). MOLECULAR MECHANISMS OF NOCICEPTION IN CHRONIC PROSTATITIS. Clinical and Preventive Medicine, (8), 126-133.


Introduction. The need to understand the pathophysiology of prostatitis is determined by its prevalence, usually chronic progressive course, significant impact on quality of life, fertility and sexuality. The modern arsenal of medicines allows us to achieve a clinically significant effect. Along with this, non-pharmacological methods are widely used to increase the effectiveness of treatment. However, despite significant successes in the treatment of prostatitis, the problems of insufficient efficiency remain unsolved by modern urology, and it is extremely difficult to help these patients. Understanding the pathophysiology of the disease has always been the key to successful diagnosis and treatment. That is why it is important to determine the mechanisms of development of painful manifestations of prostatitis.

The aim. To describe the main molecular mechanisms of tissue damage reception, in particular of the prostate gland, which are perceived as pain sensations.

Materials and methods. An evaluation of modern literature devoted to the mechanisms of creation of nerve impulses due to damage and inflammation of the prostate gland was carried out. The search was conducted in the MEDLINE and databases of the National Library of Ukraine named after V.I. Vernadsky.

Results. The main molecular mechanisms of nociception in chronic prostatitis have been determined. A review of modern literature devoted to the study of pain mechanisms as a biologically significant signal of damage at the molecular level of reception is presented. Attention is focused on the features of nociception in prostatitis, its connection with the production of inflammatory mediators, possible mechanisms of hyperalgesia and allodynia.

As a result of stress and tissue damage, the production and release of inflammatory mediators such as interleukins, interferon, prostaglandins, bradykinin, adenosine triphosphate, protons and nerve growth factor increase. These mediators activate pain receptors located on nerve endings and are ion channels of various types: transient receptor potential, acid, purinergic, and potassium ion leak channels.

Conclusions. The presented literature data describe the mechanisms of nociception, hyperalgesia and allodynia in chronic prostatitis, the understanding of which can be the basis for the development of new methods of diagnosis and treatment.
ARTICLE PDF (Українська)


Fu, X., He, H. D., Li, C. J., Li, N., Jiang, S. Y., Ge, H. W., Wang, R., & Wang, X. L. (2020). MicroRNA-155 deficiency attenuates inflammation and oxidative stress in experimental autoimmune prostatitis in a TLR4-dependent manner. The Kaohsiung journal of medical sciences, 36(9), 712–720.

Huang, J., Zhang, X., & McNaughton, P. A. (2006). Inflammatory pain: the cellular basis of heat hyperalgesia. Current neuropharmacology, 4(3), 197–206.

Alexander, R. B., Ponniah, S., Hasday, J., & Hebel, J. R. (1998). Elevated levels of proinflammatory cytokines in the semen of patients with chronic prostatitis/chronic pelvic pain syndrome. Urology, 52(5), 744–749.

Orhan, I., Onur, R., Ilhan, N., & Ardiçoglu, A. (2001). Seminal plasma cytokine levels in the diagnosis of chronic pelvic pain syndrome. International journal of urology : official journal of the Japanese Urological Association, 8(9), 495–499.

Motrich, R. D., Breser, M. L., Molina, R. I., Tissera, A., Olmedo, J. J., & Rivero, V. E. (2020). Patients with chronic prostatitis/chronic pelvic pain syndrome show T helper type 1 (Th1) and Th17 self-reactive immune responses specific to prostate and seminal antigens and diminished semen quality. BJU international, 126(3), 379–387.

M Murphy, S. F., Schaeffer, A. J., Done, J., Wong, L., Bell-Cohn, A., Roman, K., Cashy, J., Ohlhausen, M., & Thumbikat, P. (2015). IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP). PloS one, 10(5), e0125623.

Pontari, M. A., & Ruggieri, M. R. (2008). Mechanisms in prostatitis/chronic pelvic pain syndrome. The Journal of urology, 179(5 Suppl), S61–S67.

Nurimanov K.R. (2015). Effect of white blood cells and γ-interferon in sperm on fertility rates in patients with chronic abacterial prostatitis. Health of Man, (4(55), 82–84;

Miller, L. J., Fischer, K. A., Goralnick, S. J., Litt, M., Burleson, J. A., Albertsen, P., & Kreutzer, D. L. (2002). Interleukin-10 levels in seminal plasma: implications for chronic prostatitis-chronic pelvic pain syndrome. The Journal of urology, 167(2 Pt 1), 753–756.

Gorpynchenko I.I., Nurimanov K.R., Savchenko V.S., Poroshina T.V., Drannik G.M. (2017). Immune factors in the pathogenesis of inflammatory and non-inflammatory forms of chronic abacterial prostatitis. Health of Man, (4(63), 9–15;

Shulyak, A., Gorpynchenko, I., Drannik, G., Poroshina, T., Savchenko, V., & Nurimanov, K. (2019). The effectiveness of the combination of rectal electrostimulation and an antidepressant in the treatment of chronic abacterial prostatitis. Central European journal of urology, 72(1), 66–70.

Gorpynchenko, I., Nurimanov, K., Poroshina, T., Savchenko, V., Drannik, G., & Shulyak, A. (2021). Antibiotic therapy effectiveness as an outcome predictor of complex treatment in chronic prostatitis/chronic pelvic pain syndrome. Central European journal of urology, 74(2), 241–248.

Keith, I. M., Jin, J., Neal , D., Jr, Teunissen, B. D., & Moon, T. D. (2001). Cell relationship in a Wistar rat model of spontaneous prostatitis. The Journal of urology, 166(1), 323–328..

Miller, L. J., Fischer, K. A., Goralnick, S. J., Litt, M., Burleson, J. A., Albertsen, P., & Kreutzer, D. L. (2002). Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome. Urology, 59(4), 603–608. .

Rudick, C. N., Schaeffer, A. J., & Thumbikat, P. (2008). Experimental autoimmune prostatitis induces chronic pelvic pain. American journal of physiology. Regulatory, integrative and comparative physiology, 294(4), R1268–R1275. .

Wong, L., Done, J. D., Schaeffer, A. J., & Thumbikat, P. (2015). Experimental autoimmune prostatitis induces microglial activation in the spinal cord. The Prostate, 75(1), 50–59. .

Scholz, J., & Woolf, C. J. (2007). The neuropathic pain triad: neurons, immune cells and glia. Nature neuroscience, 10(11), 1361–1368.

Done, J. D., Rudick, C. N., Quick, M. L., Schaeffer, A. J., & Thumbikat, P. (2012). Role of mast cells in male chronic pelvic pain. The Journal of urology, 187(4), 1473–1482. .

Watanabe, T., Inoue, M., Sasaki, K., Araki, M., Uehara, S., Monden, K., Saika, T., Nasu, Y., Kumon, H., & Chancellor, M. B. (2011). Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment. BJU international, 108(2), 248–251. .

Tal, M., & Liberman, R. (1997). Local injection of nerve growth factor (NGF) triggers degranulation of mast cells in rat paw. Neuroscience letters, 221(2-3), 129–132. .

Lindsay, R. M., & Harmar, A. J. (1989). Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature, 337(6205), 362–364. .

Shahed, A. R., & Shoskes, D. A. (2001). Correlation of beta-endorphin and prostaglandin E2 levels in prostatic fluid of patients with chronic prostatitis with diagnosis and treatment response. The Journal of urology, 166(5), 1738–1741. .

Korkmaz, S., Karadag, M. A., Hamamcioglu, K., Sofikerim, M., & Aksu, M. (2015). Electrophysiological Identification of Central Sensitization in Patients with Chronic Prostatitis. Urology journal, 12(4), 2280–2284.

I Ishigooka, M., Zermann, D. H., Doggweiler, R., & Schmidt, R. A. (2000). Similarity of distributions of spinal c-Fos and plasma extravasation after acute chemical irritation of the bladder and the prostate. The Journal of urology, 164(5), 1751–1756.

Issberner, U., Reeh, P. W., & Steen, K. H. (1996). Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia?. Neuroscience letters, 208(3), 191–194.

Dev Deval, E., Noël, J., Lay, N., Alloui, A., Diochot, S., Friend, V., Jodar, M., Lazdunski, M., & Lingueglia, E. (2008). ASIC3, a sensor of acidic and primary inflammatory pain. The EMBO journal, 27(22), 3047–3055.

Zhang, N., Inan, S., Cowan, A., Sun, R., Wang, J. M., Rogers, T. J., Caterina, M., & Oppenheim, J. J. (2005). A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Proceedings of the National Academy of Sciences of the United States of America, 102(12), 4536–4541.

Hardie R. C. (2011). A brief history of trp: commentary and personal perspective. Pflugers Archiv : European journal of physiology, 461(5), 493–498.

Zheng J. (2013). Molecular mechanism of TRP channels. Comprehensive Physiology, 3(1), 221–242.

Light, A. R., Hughen, R. W., Zhang, J., Rainier, J., Liu, Z., & Lee, J. (2008). Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1. Journal of neurophysiology, 100(3), 1184–1201.

Gomtsyan A, Faltynek CR. (2010) Vanilloid receptor TRPV1 in drug discovery: targeting pain and other pathological disorders. Hoboken, NJ: John Wiley & Sons, (pp.151 - 174). DOI: 10.1002/9780470588284.ch5.

Ji, R. R., Samad, T. A., Jin, S. X., Schmoll, R., & Woolf, C. J. (2002). p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron, 36(1), 57–68.

Rong, W., Hillsley, K., Davis, J. B., Hicks, G., Winchester, W. J., & Grundy, D. (2004). Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. The Journal of physiology, 560(Pt 3), 867–881.

Caterina, M. J., & Julius, D. (2001). The vanilloid receptor: a molecular gateway to the pain pathway. Annual review of neuroscience, 24, 487–517.

Chizh, B. A., O'Donnell, M. B., Napolitano, A., Wang, J., Brooke, A. C., Aylott, M. C., Bullman, J. N., Gray, E. J., Lai, R. Y., Williams, P. M., & Appleby, J. M. (2007). The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain, 132(1-2), 132–141.

Roman, K., Hall, C., Schaeffer, A. J., & Thumbikat, P. (2020). TRPV1 in experimental autoimmune prostatitis. The Prostate, 80(1), 28–37.

Morenilla-Palao, C., Planells-Cases, R., García-Sanz, N., & Ferrer-Montiel, A. (2004). Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. The Journal of biological chemistry, 279(24), 25665–25672.

Dunn, P. M., Zhong, Y., & Burnstock, G. (2001). P2X receptors in peripheral neurons. Progress in neurobiology, 65(2), 107–134.

Cockayne, D. A., Hamilton, S. G., Zhu, Q. M., Dunn, P. M., Zhong, Y., Novakovic, S., Malmberg, A. B., Cain, G., Berson, A., Kassotakis, L., Hedley, L., Lachnit, W. G., Burnstock, G., McMahon, S. B., & Ford, A. P. (2000). Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature, 407(6807), 1011–1015.

Sharp CJ, Reeve AJ, Collins SD, et al. Investigation into the role of P2X(3)/P2X(2/3) receptors in neuropathic pain following chronic constriction injury in the rat: an electrophysiological study. Br J Pharmacol. 2006;148(6):845-852;

Sharp, C. J., Reeve, A. J., Collins, S. D., Martindale, J. C., Summerfield, S. G., Sargent, B. S., Bate, S. T., & Chessell, I. P. (2006). Investigation into the role of P2X(3)/P2X(2/3) receptors in neuropathic pain following chronic constriction injury in the rat: an electrophysiological study. British journal of pharmacology, 148(6), 845–852.

Weng, Z. J., Wu, L. Y., Zhou, C. L., Dou, C. Z., Shi, Y., Liu, H. R., & Wu, H. G. (2015). Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome. Purinergic signalling, 11(3), 321–329.

Zhang, H., Liu, L., Yang, Z., Pan, J., Chen, Z., Fang, Q., Li, W., Li, L., Lu, G., & Zhou, Z. (2013). P2X7 receptor mediates activation of microglial cells in prostate of chemically irritated rats. International braz j urol : official journal of the Brazilian Society of Urology, 39(2), 276–285.

Ledeboer, A., Sloane, E. M., Milligan, E. D., Frank, M. G., Mahony, J. H., Maier, S. F., & Watkins, L. R. (2005). Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain, 115(1-2), 71–83.

Enyedi, P., & Czirják, G. (2010). Molecular background of leak K+ currents: two-pore domain potassium channels. Physiological reviews, 90(2), 559–605.

Alloui, A., Zimmermann, K., Mamet, J., Duprat, F., Noël, J., Chemin, J., Guy, N., Blondeau, N., Voilley, N., Rubat-Coudert, C., Borsotto, M., Romey, G., Heurteaux, C., Reeh, P., Eschalier, A., & Lazdunski, M. (2006). TREK-1, a K+ channel involved in polymodal pain perception. The EMBO journal, 25(11), 2368–2376.

Noël, J., Zimmermann, K., Busserolles, J., Deval, E., Alloui, A., Diochot, S., Guy, N., Borsotto, M., Reeh, P., Eschalier, A., & Lazdunski, M. (2009). The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. The EMBO journal, 28(9), 1308–1318.

Marsh, B., Acosta, C., Djouhri, L., & Lawson, S. N. (2012). Leak K⁺ channel mRNAs in dorsal root ganglia: relation to inflammation and spontaneous pain behaviour. Molecular and cellular neurosciences, 49(3), 375–386.

Kang, D., Choe, C., & Kim, D. (2005). Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. The Journal of physiology, 564(Pt 1), 103–116.

Maingret, F., Lauritzen, I., Patel, A. J., Heurteaux, C., Reyes, R., Lesage, F., Lazdunski, M., & Honoré, E. (2000). TREK-1 is a heat-activated background K(+) channel. The EMBO journal, 19(11), 2483–2491.

Fink, M., Lesage, F., Duprat, F., Heurteaux, C., Reyes, R., Fosset, M., & Lazdunski, M. (1998). A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. The EMBO journal, 17(12), 3297–3308.

Kim, Y., Bang, H., Gnatenco, C., & Kim, D. (2001). Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali. Pflugers Archiv : European journal of physiology, 442(1), 64–72.

Cohen, A., Ben-Abu, Y., Hen, S., & Zilberberg, N. (2008). A novel mechanism for human K2P2.1 channel gating. Facilitation of C-type gating by protonation of extracellular histidine residues. The Journal of biological chemistry, 283(28), 19448–19455.

Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M., & Honoré, E. (1999). Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. The Journal of biological chemistry, 274(38), 26691–26696.

Zhang, J., Cao, M., Chen, Y., Wan, Z., Wang, H., Lin, H., Liang, W., & Liang, Y. (2018). Increased Expression of TREK-1 K+ Channel in the Dorsal Root Ganglion of Rats with Detrusor Overactivity After Partial Bladder Outlet Obstruction. Medical science monitor : international medical journal of experimental and clinical research, 24, 1064–1071.

Han, H. J., Lee, S. W., Kim, G. T., Kim, E. J., Kwon, B., Kang, D., Kim, H. J., & Seo, K. S. (2016). Enhanced Expression of TREK-1 Is Related with Chronic Constriction Injury of Neuropathic Pain Mouse Model in Dorsal Root Ganglion. Biomolecules & therapeutics, 24(3), 252–259.

Schwartz, E. S., Xie, A., La, J. H., & Gebhart, G. F. (2015). Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis. Pain, 156(8), 1537–1544.

La, J. H., & Gebhart, G. F. (2011). Colitis decreases mechanosensitive K2P channel expression and function in mouse colon sensory neurons. American journal of physiology. Gastrointestinal and liver physiology, 301(1), G165–G174.

Shoskes, D. A., Keslar, K. S., Gotwald, P., Berglund, R., & Vij, S. (2021). Neuroinflammatory gene expression in chronic prostatitis/chronic pelvic pain syndrome patients: insights into etiology and phenotype biology. Translational andrology and urology, 10(8), 3340–3347.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.