Main Article Content
Abstract
Pain is a complex physiological and psychological phenomenon that serves as a protective mechanism to alert the body to potential or actual tissue damage. It is broadly classified into nociceptive pain, neuropathic pain, and psychogenic pain, each with distinct mechanisms and clinical implications. Nociceptive pain arises from tissue damage and is further divided into somatic and visceral pain. Neuropathic pain results from nerve damage or dysfunction, often presenting as burning, tingling, or shooting sensations. Psychogenic pain is influenced by psychological factors, though it may coexist with physical causes. The pathophysiology of pain involves the activation of nociceptors, peripheral and central sensitization, and the modulation of pain signals by neurotransmitters such as substance P, glutamate, and endorphins. Chronic pain conditions often involve maladaptive changes in the nervous system, leading to hyperalgesia (increased pain sensitivity) and allodynia (pain from normally non-painful stimuli). Treatment strategies for pain management include pharmacological and non-pharmacological approaches. Pharmacological treatments involve the use of nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, anticonvulsants, antidepressants, and local anesthetics, depending on the type and severity of pain. Non-pharmacological approaches such as physical therapy, cognitive-behavioral therapy (CBT), acupuncture, and neuromodulation techniques are also employed to improve pain relief and patient quality of life. A multimodal approach to pain management is often necessary, particularly in chronic pain conditions, to address both the physical and psychological aspects of pain. Advancements in pain research, including gene therapy and novel analgesic drug development, continue to improve treatment outcomes and provide better patient care.
Keywords
Pain
Acute pain
Chronic Pain
Phanom pain
Article Details
How to Cite
Understanding Pain: Types, Pathophysiology and Modern Treatment Approaches. (2025). International Journal of Research in Pharmacology & Pharmacotherapeutics, 14(3), 316-333. https://ijrpp.com/ijrpp/article/view/703
How to Cite
Understanding Pain: Types, Pathophysiology and Modern Treatment Approaches. (2025). International Journal of Research in Pharmacology & Pharmacotherapeutics, 14(3), 316-333. https://ijrpp.com/ijrpp/article/view/703
References
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1. Rodriguez-Raecke, R., Niemeier, A., Ihle, K., Ruether, W., & May, A. (2009). Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. Journal of Neuroscience, 29(44), 13746–13750. https://doi.org/10.1523/jneurosci.3687-09.2009
2. Watson, J. C., & Sandroni, P. (2016). Central Neuropathic Pain Syndromes. Mayo Clinic proceedings, 91(3), 372–385. https://doi.org/10.1016/j.mayocp.2016.01.017
3. Milani, D. a. Q., & Davis, D. D. (2023, July 3). Pain management medications. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK560692/
4. Jin, Q., Chang, Y., Lu, C., Chen, L., & Wang, Y. (2023). Referred pain: characteristics, possible mechanisms, and clinical management. Frontiers in Neurology, 14. https://doi.org/10.3389/fneur.2023.1104817
5. A review of the general aspects of radiofrequency ablation. (2005). In Abdominal Imaging (Vol. 30, pp. 381–400). https://doi.org/10.1007/s00261-004-0253-9
6. Zeckser, J., Wolff, M., Tucker, J., & Goodwin, J. (2016). Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells International, 2016, 1–13. https://doi.org/10.1155/2016/3908389
7. Li, M., Li, J., Chen, H., & Zhu, M. (2023). VEGF-Expressing mesenchymal stem cell therapy for safe and effective treatment of pain in Parkinson’s disease. Cell Transplantation, 32. https://doi.org/10.1177/09636897221149130
8. Vickers, R., Karsten, E., Lilischkis, R., & Flood, J. (2014). A preliminary report on stem cell therapy for neuropathic pain in humans. Journal of Pain Research, 255. https://doi.org/10.2147/jpr.s63361
9. Yousefifard, M., Nasirinezhad, F., Manaheji, H. S., Janzadeh, A., Hosseini, M., & Keshavarz, M. (2016). Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model. Stem Cell Research & Therapy, 7(1). https://doi.org/10.1186/s13287-016-0295-2
10. Babaie, S., Taghvimi, A., Hong, J.-H., Hamishehkar, H., An, S., & Kim, K. H. (2022). Recent advances in pain management based on nanoparticle technologies. Journal of Nanobiotechnology, 20, 290. https://doi.org/10.1186/s12951-022-01473-y
11. Recent advances in zinc oxide nanoparticles (ZNO NPs) for cancer diagnosis, target drug delivery, and treatment. (2021). Cancers, 4570. https://doi.org/10.3390/cancers13184570
12. Wolfe, D., Wechuck, J., Krisky, D., Mata, M., & Fink, D. J. (2009). A clinical trial of gene therapy for chronic pain. Pain Medicine, 10(7), 1325–1330. https://doi.org/10.1111/j.1526-4637.2009.00720.x
13. Madsen, M. V., Gotzsche, P. C., & Hrobjartsson, A. (2009). Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ, 338(jan27 2), a3115. https://doi.org/10.1136/bmj.a3115
14. Kelly, R. B., Willis, J., & Cleveland Clinic Family Medicine Residency. (2019). Acupuncture for pain. In American Family Physician (pp. 89–96). https://www.aafp.org/pubs/afp/issues/2019/0715/p89.pdf
15. Why acupuncture in pain treatment? (2016). In Neuroendocrinology Letters (Vol. 37, Issue 3, pp. 163–168). Neuroendocrinology Letters. https://www.nel.edu
16. Professional, C. C. M. (2024, October 11). Somatic pain. Cleveland Clinic. https://my.clevelandclinic.org/health/symptoms/somatic-pain
17. Foulkes, T., & Wood, J. N. (2008). Pain genes. In PLoS Genet (Vol. 7, p. e1000086). https://doi.org/10.1371/journal.pgen.1000086
18. Olbert, M., Gdula-Argasińska, J., Nowak, G., & Librowski, T. (2017). Beneficial effect of nanoparticles over standard form of zinc oxide in enhancing the anti-inflammatory activity of ketoprofen in rats. Pharmacological reports : PR, 69(4), 679–682. https://doi.org/10.1016/j.pharep.2017.02.004
19. Chua, N. H. L., Vissers, K. C., & Sluijter, M. E. (2010). Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications—a review. Acta Neurochirurgica, 153(4), 763–771. https://doi.org/10.1007/s00701-010-0881-5
20. Choi, W., Hwang, S., Song, J., Leem, J., Kang, Y., Park, P., & Shin, J. (2011). Radiofrequency treatment relieves chronic knee osteoarthritis pain: A double-blind randomized controlled trial. Pain, 152(3), 481–487. https://doi.org/10.1016/j.pain.2010.09.029
21. Wei, X., Yang, X., Han, Z., Qu, F., Shao, L., & Shi, Y. (2013). Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacologica Sinica, 34(6), 747–754. https://doi.org/10.1038/aps.2013.50
22. Hawker, G. A., Mian, S., Kendzerska, T., & French, M. (2011). Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short‐Form McGill Pain Questionnaire (SF‐MPQ), Chronic Pain Grade Scale (CPGS), Short Form‐36 Bodily Pain Scale (SF‐36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care & Research, 63(S11). https://doi.org/10.1002/acr.20543
23. Farrar, J. T., Jr. Young, J. P., Linda LaMoreaux, John L. Werth, & R. Michael Poole. (2001). Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. In Pain (Vol. 94, pp. 149–158) [Journal-article]. https://doi.org/10.1016/S0304-3959(01)00349-9
24. Quinlan, J., & Cox, F. (2017). Acute pain management in patients with drug dependence syndrome. PAIN Reports, 2(4), e611. https://doi.org/10.1097/pr9.0000000000000611
References
1. Rodriguez-Raecke, R., Niemeier, A., Ihle, K., Ruether, W., & May, A. (2009). Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. Journal of Neuroscience, 29(44), 13746–13750. https://doi.org/10.1523/jneurosci.3687-09.2009
2. Watson, J. C., & Sandroni, P. (2016). Central Neuropathic Pain Syndromes. Mayo Clinic proceedings, 91(3), 372–385. https://doi.org/10.1016/j.mayocp.2016.01.017
3. Milani, D. a. Q., & Davis, D. D. (2023, July 3). Pain management medications. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK560692/
4. Jin, Q., Chang, Y., Lu, C., Chen, L., & Wang, Y. (2023). Referred pain: characteristics, possible mechanisms, and clinical management. Frontiers in Neurology, 14. https://doi.org/10.3389/fneur.2023.1104817
5. A review of the general aspects of radiofrequency ablation. (2005). In Abdominal Imaging (Vol. 30, pp. 381–400). https://doi.org/10.1007/s00261-004-0253-9
6. Zeckser, J., Wolff, M., Tucker, J., & Goodwin, J. (2016). Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells International, 2016, 1–13. https://doi.org/10.1155/2016/3908389
7. Li, M., Li, J., Chen, H., & Zhu, M. (2023). VEGF-Expressing mesenchymal stem cell therapy for safe and effective treatment of pain in Parkinson’s disease. Cell Transplantation, 32. https://doi.org/10.1177/09636897221149130
8. Vickers, R., Karsten, E., Lilischkis, R., & Flood, J. (2014). A preliminary report on stem cell therapy for neuropathic pain in humans. Journal of Pain Research, 255. https://doi.org/10.2147/jpr.s63361
9. Yousefifard, M., Nasirinezhad, F., Manaheji, H. S., Janzadeh, A., Hosseini, M., & Keshavarz, M. (2016). Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model. Stem Cell Research & Therapy, 7(1). https://doi.org/10.1186/s13287-016-0295-2
10. Babaie, S., Taghvimi, A., Hong, J.-H., Hamishehkar, H., An, S., & Kim, K. H. (2022). Recent advances in pain management based on nanoparticle technologies. Journal of Nanobiotechnology, 20, 290. https://doi.org/10.1186/s12951-022-01473-y
11. Recent advances in zinc oxide nanoparticles (ZNO NPs) for cancer diagnosis, target drug delivery, and treatment. (2021). Cancers, 4570. https://doi.org/10.3390/cancers13184570
12. Wolfe, D., Wechuck, J., Krisky, D., Mata, M., & Fink, D. J. (2009). A clinical trial of gene therapy for chronic pain. Pain Medicine, 10(7), 1325–1330. https://doi.org/10.1111/j.1526-4637.2009.00720.x
13. Madsen, M. V., Gotzsche, P. C., & Hrobjartsson, A. (2009). Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ, 338(jan27 2), a3115. https://doi.org/10.1136/bmj.a3115
14. Kelly, R. B., Willis, J., & Cleveland Clinic Family Medicine Residency. (2019). Acupuncture for pain. In American Family Physician (pp. 89–96). https://www.aafp.org/pubs/afp/issues/2019/0715/p89.pdf
15. Why acupuncture in pain treatment? (2016). In Neuroendocrinology Letters (Vol. 37, Issue 3, pp. 163–168). Neuroendocrinology Letters. https://www.nel.edu
16. Professional, C. C. M. (2024, October 11). Somatic pain. Cleveland Clinic. https://my.clevelandclinic.org/health/symptoms/somatic-pain
17. Foulkes, T., & Wood, J. N. (2008). Pain genes. In PLoS Genet (Vol. 7, p. e1000086). https://doi.org/10.1371/journal.pgen.1000086
18. Olbert, M., Gdula-Argasińska, J., Nowak, G., & Librowski, T. (2017). Beneficial effect of nanoparticles over standard form of zinc oxide in enhancing the anti-inflammatory activity of ketoprofen in rats. Pharmacological reports : PR, 69(4), 679–682. https://doi.org/10.1016/j.pharep.2017.02.004
19. Chua, N. H. L., Vissers, K. C., & Sluijter, M. E. (2010). Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications—a review. Acta Neurochirurgica, 153(4), 763–771. https://doi.org/10.1007/s00701-010-0881-5
20. Choi, W., Hwang, S., Song, J., Leem, J., Kang, Y., Park, P., & Shin, J. (2011). Radiofrequency treatment relieves chronic knee osteoarthritis pain: A double-blind randomized controlled trial. Pain, 152(3), 481–487. https://doi.org/10.1016/j.pain.2010.09.029
21. Wei, X., Yang, X., Han, Z., Qu, F., Shao, L., & Shi, Y. (2013). Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacologica Sinica, 34(6), 747–754. https://doi.org/10.1038/aps.2013.50
22. Hawker, G. A., Mian, S., Kendzerska, T., & French, M. (2011). Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short‐Form McGill Pain Questionnaire (SF‐MPQ), Chronic Pain Grade Scale (CPGS), Short Form‐36 Bodily Pain Scale (SF‐36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care & Research, 63(S11). https://doi.org/10.1002/acr.20543
23. Farrar, J. T., Jr. Young, J. P., Linda LaMoreaux, John L. Werth, & R. Michael Poole. (2001). Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. In Pain (Vol. 94, pp. 149–158) [Journal-article]. https://doi.org/10.1016/S0304-3959(01)00349-9
24. Quinlan, J., & Cox, F. (2017). Acute pain management in patients with drug dependence syndrome. PAIN Reports, 2(4), e611. https://doi.org/10.1097/pr9.0000000000000611
2. Watson, J. C., & Sandroni, P. (2016). Central Neuropathic Pain Syndromes. Mayo Clinic proceedings, 91(3), 372–385. https://doi.org/10.1016/j.mayocp.2016.01.017
3. Milani, D. a. Q., & Davis, D. D. (2023, July 3). Pain management medications. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK560692/
4. Jin, Q., Chang, Y., Lu, C., Chen, L., & Wang, Y. (2023). Referred pain: characteristics, possible mechanisms, and clinical management. Frontiers in Neurology, 14. https://doi.org/10.3389/fneur.2023.1104817
5. A review of the general aspects of radiofrequency ablation. (2005). In Abdominal Imaging (Vol. 30, pp. 381–400). https://doi.org/10.1007/s00261-004-0253-9
6. Zeckser, J., Wolff, M., Tucker, J., & Goodwin, J. (2016). Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells International, 2016, 1–13. https://doi.org/10.1155/2016/3908389
7. Li, M., Li, J., Chen, H., & Zhu, M. (2023). VEGF-Expressing mesenchymal stem cell therapy for safe and effective treatment of pain in Parkinson’s disease. Cell Transplantation, 32. https://doi.org/10.1177/09636897221149130
8. Vickers, R., Karsten, E., Lilischkis, R., & Flood, J. (2014). A preliminary report on stem cell therapy for neuropathic pain in humans. Journal of Pain Research, 255. https://doi.org/10.2147/jpr.s63361
9. Yousefifard, M., Nasirinezhad, F., Manaheji, H. S., Janzadeh, A., Hosseini, M., & Keshavarz, M. (2016). Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model. Stem Cell Research & Therapy, 7(1). https://doi.org/10.1186/s13287-016-0295-2
10. Babaie, S., Taghvimi, A., Hong, J.-H., Hamishehkar, H., An, S., & Kim, K. H. (2022). Recent advances in pain management based on nanoparticle technologies. Journal of Nanobiotechnology, 20, 290. https://doi.org/10.1186/s12951-022-01473-y
11. Recent advances in zinc oxide nanoparticles (ZNO NPs) for cancer diagnosis, target drug delivery, and treatment. (2021). Cancers, 4570. https://doi.org/10.3390/cancers13184570
12. Wolfe, D., Wechuck, J., Krisky, D., Mata, M., & Fink, D. J. (2009). A clinical trial of gene therapy for chronic pain. Pain Medicine, 10(7), 1325–1330. https://doi.org/10.1111/j.1526-4637.2009.00720.x
13. Madsen, M. V., Gotzsche, P. C., & Hrobjartsson, A. (2009). Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ, 338(jan27 2), a3115. https://doi.org/10.1136/bmj.a3115
14. Kelly, R. B., Willis, J., & Cleveland Clinic Family Medicine Residency. (2019). Acupuncture for pain. In American Family Physician (pp. 89–96). https://www.aafp.org/pubs/afp/issues/2019/0715/p89.pdf
15. Why acupuncture in pain treatment? (2016). In Neuroendocrinology Letters (Vol. 37, Issue 3, pp. 163–168). Neuroendocrinology Letters. https://www.nel.edu
16. Professional, C. C. M. (2024, October 11). Somatic pain. Cleveland Clinic. https://my.clevelandclinic.org/health/symptoms/somatic-pain
17. Foulkes, T., & Wood, J. N. (2008). Pain genes. In PLoS Genet (Vol. 7, p. e1000086). https://doi.org/10.1371/journal.pgen.1000086
18. Olbert, M., Gdula-Argasińska, J., Nowak, G., & Librowski, T. (2017). Beneficial effect of nanoparticles over standard form of zinc oxide in enhancing the anti-inflammatory activity of ketoprofen in rats. Pharmacological reports : PR, 69(4), 679–682. https://doi.org/10.1016/j.pharep.2017.02.004
19. Chua, N. H. L., Vissers, K. C., & Sluijter, M. E. (2010). Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications—a review. Acta Neurochirurgica, 153(4), 763–771. https://doi.org/10.1007/s00701-010-0881-5
20. Choi, W., Hwang, S., Song, J., Leem, J., Kang, Y., Park, P., & Shin, J. (2011). Radiofrequency treatment relieves chronic knee osteoarthritis pain: A double-blind randomized controlled trial. Pain, 152(3), 481–487. https://doi.org/10.1016/j.pain.2010.09.029
21. Wei, X., Yang, X., Han, Z., Qu, F., Shao, L., & Shi, Y. (2013). Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacologica Sinica, 34(6), 747–754. https://doi.org/10.1038/aps.2013.50
22. Hawker, G. A., Mian, S., Kendzerska, T., & French, M. (2011). Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short‐Form McGill Pain Questionnaire (SF‐MPQ), Chronic Pain Grade Scale (CPGS), Short Form‐36 Bodily Pain Scale (SF‐36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care & Research, 63(S11). https://doi.org/10.1002/acr.20543
23. Farrar, J. T., Jr. Young, J. P., Linda LaMoreaux, John L. Werth, & R. Michael Poole. (2001). Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. In Pain (Vol. 94, pp. 149–158) [Journal-article]. https://doi.org/10.1016/S0304-3959(01)00349-9
24. Quinlan, J., & Cox, F. (2017). Acute pain management in patients with drug dependence syndrome. PAIN Reports, 2(4), e611. https://doi.org/10.1097/pr9.0000000000000611