Nociceptive, Neuropathic and Nociplastic Pain in Clinical Practice: Mechanism-Oriented Assessment and Multimodal Management - Systematic Review
DOI:
https://doi.org/10.12775/QS.2026.52.68835Keywords
Chronic pain, nociplastic pain, neuropathic pain, Central Sensitization, pain-management, non-pharmacological pain manegement, pharmacological treatmentAbstract
Background: Chronic pain is common and increasingly considered a disease - anatomical labels often fail to reflect sustaining mechanisms. The IASP/ICD-11 framework classifies pain as nociceptive, neuropathic, and nociplastic, which often coexist.
Aim: To synthesize mechanisms of nociceptive, neuropathic, nociplastic, and mixed pain, and outline a mechanism-oriented, multimodal management approach.
Methods: Narrative review of major guidelines, systematic reviews, and pivotal clinical trials.
Results: Nociceptive pain reflects ongoing peripheral nociceptor activation and peripheral sensitization; management targets the tissue source and inflammation. Neuropathic pain follows a lesion or disease of the somatosensory system with ectopic firing, neuroinflammation, and central sensitization; first-line drugs include tricyclic antidepressants, SNRIs, and gabapentinoids, while NSAIDs show little benefit in pure neuropathic states. Nociplastic pain involves altered nociceptive processing without clear tissue damage or nerve lesion and is linked to central sensitization, widespread hypersensitivity, fatigue, and sleep/cognitive symptoms; education, graded exercise, and cognitive-behavioral strategies are foundational. Mixed states are common, and sustained peripheral input may promote “centralization,” requiring individualized combinations of therapies. In selected, well-phenotyped neuropathic syndromes, interventional options (e.g., blocks, steroid injections, pulsed radiofrequency, botulinum toxin A, neuromodulation) can be useful adjuncts to rehabilitation and optimized medication.
Conclusion: Mechanism-based assessment supports rational, individualized therapy selection. Effective care is multimodal, addressing peripheral generators, neural hyperexcitability, central sensitization, and psychosocial factors, with realistic goals emphasizing function and quality of life.
References
1. Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, et al. A classification of chronic pain for ICD-11. Pain. czerwca 2015;156(6):1003-7.
2. Barke A, Korwisi B, Rief W. Chronic Pain in the ICD-11: New Diagnoses That Clinical Psychologists Should Know About. Clin Psychol Eur. grudnia 2022;4(Spec Issue):e9933.
3. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 1 września 2020;161(9):1976-82.
4. Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primer. 16 lutego 2017;3:17002.
5. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol. września 2014;13(9):924-35.
6. Kosek E, Cohen M, Baron R, Gebhart GF, Mico JA, Rice ASC, et al. Do we need a third mechanistic descriptor for chronic pain states? Pain. lipca 2016;157(7):1382-6.
7. Nijs J, Lahousse A, Kapreli E, Bilika P, Saraçoğlu İ, Malfliet A, et al. Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future. J Clin Med. 21 lipca 2021;10(15):3203.
8. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 16 kwietnia 2014;311(15):1547-55.
9. Freynhagen R, Parada HA, Calderon-Ospina CA, Chen J, Rakhmawati Emril D, Fernández-Villacorta FJ, et al. Current understanding of the mixed pain concept: a brief narrative review. Curr Med Res Opin. czerwca 2019;35(6):1011-8.
10. van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth. lipca 2013;111(1):13-8.
11. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 16 października 2009;139(2):267-84.
12. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 9 czerwca 2000;288(5472):1765-9.
13. Schaible HG. Mechanisms of chronic pain in osteoarthritis. Curr Rheumatol Rep. grudnia 2012;14(6):549-56.
14. Finnerup NB, Kuner R, Jensen TS. Neuropathic Pain: From Mechanisms to Treatment. Physiol Rev. 1 stycznia 2021;101(1):259-301.
15. Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1-32.
16. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. września 2009;10(9):895-926.
17. Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy? Pain. grudnia 2013;154 Suppl 1(0 1):S10-28.
18. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain Lond Engl. sierpnia 2005;9(4):463-84.
19. Taylor AMW, Becker S, Schweinhardt P, Cahill C. Mesolimbic dopamine signaling in acute and chronic pain: implications for motivation, analgesia, and addiction. Pain. czerwca 2016;157(6):1194-8.
20. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. marca 2011;152(3 Suppl):S2-15.
21. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. lutego 2015;14(2):162-73.
22. Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. września 2010;17(9):1113-e88.
23. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. sierpnia 2010;9(8):807-19.
24. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 5 grudnia 2007;132(3):237-51.
25. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 29 kwietnia 2008;70(18):1630-5.
26. Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. stycznia 2019;160(1):53-9.
27. Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Cochrane Database Syst Rev. 11 listopada 2013;2013(11):CD010567.
28. Neuropathic pain in adults: pharmacological management in non-specialist settings [Internet]. London: National Institute for Health and Care Excellence (NICE); 2020 [cytowane 12 grudnia 2025]. (National Institute for Health and Care Excellence: Guidelines). Dostępne na: http://www.ncbi.nlm.nih.gov/books/NBK552848/
29. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 5 grudnia 2005;118(3):289-305.
30. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. października 2009;122(10 Suppl):S22-32.
31. Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. lipca 2007;133(4):581-624.
32. Moore RA, Chi CC, Wiffen PJ, Derry S, Rice ASC. Oral nonsteroidal anti-inflammatory drugs for neuropathic pain. Cochrane Database Syst Rev. 5 października 2015;2015(10):CD010902.
33. Moisset X, Bouhassira D, Avez Couturier J, Alchaar H, Conradi S, Delmotte MH, et al. Pharmacological and non-pharmacological treatments for neuropathic pain: Systematic review and French recommendations. Rev Neurol (Paris). maja 2020;176(5):325-52.
34. Vo T, Rice ASC, Dworkin RH. Non-steroidal anti-inflammatory drugs for neuropathic pain: how do we explain continued widespread use? Pain. czerwca 2009;143(3):169-71.
35. Hopkins S, Yang V, Liew DF. Choosing a nonsteroidal anti-inflammatory drug for pain. Aust Prescr. sierpnia 2025;48(4):139-44.
36. Varrassi G, Farì G, Narvaez Tamayo MA, Gomez MP, Guerrero Liñeiro AM, Pereira CL, et al. Mixed pain: clinical practice recommendations. Front Med. 2025;12:1659490.
37. Varga Z, Sabzwari SRA, Vargova V. Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized Public Health Issue. Cureus. 8 kwietnia 2017;9(4):e1144.
38. Pop-Busui R, Boulton AJM, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. stycznia 2017;40(1):136-54.
39. Obata H. Analgesic Mechanisms of Antidepressants for Neuropathic Pain. Int J Mol Sci. 21 listopada 2017;18(11):2483.
40. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 17 października 2007;2007(4):CD005454.
41. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. czerwca 2005;96(6):399-409.
42. Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 3 stycznia 2014;2014(1):CD007115.
43. Sultan A, Gaskell H, Derry S, Moore RA. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials. BMC Neurol. 1 sierpnia 2008;8:29.
44. Semenchuk MR, Davis B. Efficacy of sustained-release bupropion in neuropathic pain: an open-label study. Clin J Pain. marca 2000;16(1):6-11.
45. Cording M, Derry S, Phillips T, Moore RA, Wiffen PJ. Milnacipran for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 20 października 2015;2015(10):CD008244.
46. Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev. 23 stycznia 2019;1(1):CD007076.
47. Zakrzewska JM, Linskey ME. Trigeminal neuralgia. BMJ. 17 lutego 2014;348:g474.
48. Wiffen PJ, Derry S, Moore RA. Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 3 grudnia 2013;2013(12):CD006044.
49. Duehmke RM, Derry S, Wiffen PJ, Bell RF, Aldington D, Moore RA. Tramadol for neuropathic pain in adults. Cochrane Database Syst Rev. 15 czerwca 2017;6(6):CD003726.
50. Quintero JM, Pulido G, Giraldo LF, Leon MX, Diaz LE, Bustos RH. A Systematic Review on Cannabinoids for Neuropathic Pain Administered by Routes Other than Oral or Inhalation. Plants Basel Switz. 20 maja 2022;11(10):1357.
51. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 7 marca 2018;3(3):CD012182.
52. Petzke F, Enax-Krumova EK, Häuser W. [Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies]. Schmerz Berl Ger. lutego 2016;30(1):62-88.
53. Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015;29(1):7-14.
54. O’Brien K, Beilby J, Frans M, Lynskey M, Barnes M, Jayasuriya M, et al. Medicinal cannabis for pain: Real-world data on three-month changes in symptoms and quality of life. Drug Sci Policy Law. stycznia 2023;9:20503245231172535.
55. Goel A. Review: In chronic noncancer pain, cannabinoids reduce pain (NNT 24) but increase adverse events (NNH 6). Ann Intern Med. 18 grudnia 2018;169(12):JC62.
56. Sommer C, Cruccu G. Topical Treatment of Peripheral Neuropathic Pain: Applying the Evidence. J Pain Symptom Manage. marca 2017;53(3):614-29.
57. Casale R, Symeonidou Z, Bartolo M. Topical Treatments for Localized Neuropathic Pain. Curr Pain Headache Rep. marca 2017;21(3):15.
58. Kocot-Kępska M, Zajączkowska R, Mika J, Kopsky DJ, Wordliczek J, Dobrogowski J, et al. Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review. Pharmaceutics. 26 marca 2021;13(4):450.
59. Lawson E, Singla P, Adler J, Argoff CE, Bettinger JJ, Bhaskar A, et al. Topical analgesics for neuropathic pain: An Evidence-Informed guide for the practicing clinician. Pain Med Malden Mass. 29 września 2025;pnaf130.
60. Liu X, Wei L, Zeng Q, Lin K, Zhang J. The Treatment of Topical Drugs for Postherpetic Neuralgia: A Network Meta-Analysis. Pain Physician. listopada 2020;23(6):541-51.
61. Kaye AD, Armistead G, Amedio LS, Manthei ME, Ahmadzadeh S, Bernhardt B, et al. Evolving Treatment Strategies for Neuropathic Pain: A Narrative Review. Med Kaunas Lith. 10 czerwca 2025;61(6):1063.
62. Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee: a Cochrane systematic review. Br J Sports Med. grudnia 2015;49(24):1554-7.
63. Hayden JA, Ellis J, Ogilvie R, Stewart SA, Bagg MK, Stanojevic S, et al. Some types of exercise are more effective than others in people with chronic low back pain: a network meta-analysis. J Physiother. października 2021;67(4):252-62.
64. Ellis RF, Hing WA. Neural mobilization: a systematic review of randomized controlled trials with an analysis of therapeutic efficacy. J Man Manip Ther. 2008;16(1):8-22.
65. Moseley GL. Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial. Pain. marca 2004;108(1-2):192-8.
66. Busch AJ, Webber SC, Richards RS, Bidonde J, Schachter CL, Schafer LA, et al. Resistance exercise training for fibromyalgia. Cochrane Database Syst Rev. 20 grudnia 2013;2013(12):CD010884.
67. Wang C, Schmid CH, Rones R, Kalish R, Yinh J, Goldenberg DL, et al. A randomized trial of tai chi for fibromyalgia. N Engl J Med. 19 sierpnia 2010;363(8):743-54.
68. Ehde DM, Dillworth TM, Turner JA. Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research. Am Psychol. 2014;69(2):153-66.
69. Williams AC de C, Fisher E, Hearn L, Eccleston C. Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev. 12 sierpnia 2020;8(8):CD007407.
70. Thieme K, Mathys M, Turk DC. Evidenced-Based Guidelines on the Treatment of Fibromyalgia Patients: Are They Consistent and If Not, Why Not? Have Effective Psychological Treatments Been Overlooked? J Pain. lipca 2017;18(7):747-56.
71. DeSantana JM, Walsh DM, Vance C, Rakel BA, Sluka KA. Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain. Curr Rheumatol Rep. grudnia 2008;10(6):492-9.
72. Claydon LS, Chesterton LS, Barlas P, Sim J. Dose-specific effects of transcutaneous electrical nerve stimulation (TENS) on experimental pain: a systematic review. Clin J Pain. września 2011;27(7):635-47.
73. Vickers AJ, Cronin AM, Maschino AC, Lewith G, MacPherson H, Foster NE, et al. Acupuncture for chronic pain: individual patient data meta-analysis. Arch Intern Med. 22 października 2012;172(19):1444-53.
74. Louw A, Zimney K, Puentedura EJ, Diener I. The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the literature. Physiother Theory Pract. lipca 2016;32(5):332-55.
75. Nijs J, Van Houdenhove B, Oostendorp RAB. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther. kwietnia 2010;15(2):135-41.
76. Wood L, Hendrick PA. A systematic review and meta-analysis of pain neuroscience education for chronic low back pain: Short-and long-term outcomes of pain and disability. Eur J Pain Lond Engl. lutego 2019;23(2):234-49.
77. Abram SE. Neural blockade for neuropathic pain. Clin J Pain. czerwca 2000;16(2 Suppl):S56-61.
78. Mailis A, Taenzer P. Evidence-based guideline for neuropathic pain interventional treatments: spinal cord stimulation, intravenous infusions, epidural injections and nerve blocks. Pain Res Manag. 2012;17(3):150-8.
79. Bernetti A, Agostini F, de Sire A, Mangone M, Tognolo L, Di Cesare A, et al. Neuropathic Pain and Rehabilitation: A Systematic Review of International Guidelines. Diagn Basel Switz. 5 stycznia 2021;11(1):74.
80. Varshney V, Osborn J, Chaturvedi R, Shah V, Chakravarthy K. Advances in the interventional management of neuropathic pain. Ann Transl Med. stycznia 2021;9(2):187.
81. Boswell MV, Hansen HC, Trescot AM, Hirsch JA. Epidural steroids in the management of chronic spinal pain and radiculopathy. Pain Physician. lipca 2003;6(3):319-34.
82. Cohen SP, Bicket MC, Jamison D, Wilkinson I, Rathmell JP. Epidural steroids: a comprehensive, evidence-based review. Reg Anesth Pain Med. 2013;38(3):175-200.
83. Deer TR. A review of interventional strategies for neuropathic pain. Pain Physician. 2020;23(3):E237-55.
84. Scanlon GC, Moeller-Bertram T, Romanowsky SM, Wallace MS. Cervical transforaminal epidural steroid injections: more dangerous than we think? Spine. 15 maja 2007;32(11):1249-56.
85. Neal JM, Barrington MJ, Brull R, Hadzic A, Hebl JR, Horlocker TT, et al. The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine: Executive Summary 2015. Reg Anesth Pain Med. 2015;40(5):401-30.
86. Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Leong M, et al. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation J Int Neuromodulation Soc. sierpnia 2014;17(6):515-50; discussion 550.
87. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, et al. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology. października 2015;123(4):851-60.
88. Gilmore C, Ilfeld B, Rosenow J, Li S, Desai M, Hunter C, et al. Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation pain: a multicenter, randomized, placebo-controlled trial. Reg Anesth Pain Med. czerwca 2019;44(6):637-45.
89. Deer TR, Levy RM, Kramer J, Poree L, Amirdelfan K, Grigsby E, et al. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Pain. kwietnia 2017;158(4):669-81.
90. Chua NHL, Vissers KC, Sluijter ME. Pulsed radiofrequency treatment in interventional pain management: mechanisms and potential indications-a review. Acta Neurochir (Wien). kwietnia 2011;153(4):763-71.
91. Byrd D, Mackey S. Pulsed radiofrequency for chronic pain. Curr Pain Headache Rep. stycznia 2008;12(1):37-41.
92. Vuka I, Marciuš T, Došenović S, Ferhatović Hamzić L, Vučić K, Sapunar D, et al. Efficacy and Safety of Pulsed Radiofrequency as a Method of Dorsal Root Ganglia Stimulation in Patients with Neuropathic Pain: A Systematic Review. Pain Med Malden Mass. 25 grudnia 2020;21(12):3320-43.
93. Erdine S, Ozyalcin NS, Cimen A, Celik M, Talu GK, Disci R. Comparison of pulsed radiofrequency with conventional radiofrequency in the treatment of idiopathic trigeminal neuralgia. Eur J Pain Lond Engl. kwietnia 2007;11(3):309-13.
94. Van Zundert J, Patijn J, Kessels A, Lamé I, van Suijlekom H, van Kleef M. Pulsed radiofrequency adjacent to the cervical dorsal root ganglion in chronic cervical radicular pain: a double blind sham controlled randomized clinical trial. Pain. stycznia 2007;127(1-2):173-82.
95. Jabbari B, Machado D. Treatment of refractory pain with botulinum toxins--an evidence-based review. Pain Med Malden Mass. listopada 2011;12(11):1594-606.
96. Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, et al. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. maja 2016;15(6):555-65.
97. Lakhan SE, Velasco DN, Tepper D. Botulinum Toxin-A for Painful Diabetic Neuropathy: A Meta-Analysis. Pain Med Malden Mass. września 2015;16(9):1773-80.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Mateusz Ząbek, Adam Zysk, Maciej Wojewódzki, Małgorzata Styczyńska, Jakub Z. Zalewski, Alicja Cyrzan, Bartosz Fronczak, Martyna Iwanowska, Adrian Goss, Beata Flis
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 49
Number of citations: 0
