Reviews Open access

PAIN DIAGNOSIS AND TREATMENT ACCORDING TO THE PAIN GENERATING FACTORS

Authors

Published
14 February 2025
Section
Reviews
Pages
124-132

Abstract

Chronic pain impacts on many aspects of patient life affecting autonomy, sleep, social activities and also employment. Adequate pain control is often challenging in patients with chronic pain, despite the availability of many medications and interventional techniques. Limitations to successful pain treatment are the poor understanding of contributing mechanisms and the lack of a mechanism based approach in clinical practice.
The purpose of this article is to identify the factors contributing to pain generation in order to guide a personalized treatment. We analyze tissue specificity for chemical and physical stresses potentially causing pain, the changes that occur in the peripheral and central pain pathways during disease, the stimuli that, acting on a pathological pain pathway, can trigger pain. The pain generating factors should be recognized in each patient and addressed with pharmacological, rehabilitation and invasive interventions.

References

  1. 1) de Sola H, Salazar A, Dueñas M, Ojeda B, Failde I. Nationwide cross-sectional study of the impact of chronic pain on an individual's employment: relationship with the family and the social support. BMJ Open 2016;6:e012246. doi:10.1136/bmjopen-2016-012246. 2) Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice ASC, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015; 14:162-173. DOI: https://doi.org/10.1016/S1474-4422(14)70251-0
  2. 3) Attal N, Cruccu G, Baron R, Haanpa M, Hansson P, Jensen TS and Nurmikko T. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European Journal of Neurology. 2010; 17:1113-1123. DOI: https://doi.org/10.1111/j.1468-1331.2010.02999.x
  3. ) NICE clinical guidelines 173. Neuropathic pain - pharmacologic lanagement. www.nice.org.uk/guidance/CG173. November 201. update December 2014.
  4. 5) Dworkin RH, Panarites CJ, Armstrong EP, Malone DC, Pham SV. Is treatment of postherpetic neuralgia in the community consistent with evidence-based recommendations? Pain. 2012; 153: 869-875. DOI: https://doi.org/10.1016/j.pain.2012.01.015
  5. 6) Campbell W. Current options in the drug management of nociceptive pain. Prescriber. 2007; 18(8): 61-77. DOI: https://doi.org/10.1002/psb.66
  6. 7) Chronic pain medical treatment guidelines. MTUS. 2009.
  7. 8) Woolf CJ, Max MB. Mechanism-based Pain Diagnosis: Issues for Analgesic Drug Development. Anesthesiology. 2001; 95: 241-249. 9) Vardeh D, Mannion RJ, Woolf CJ. Toward a Mechanism-Based Approach to Pain Diagnosis. J Pain. 2016; 17(9), Suppl 2: T50-T69. 10) Clauw DJ. Fibromyalgia and Related Conditions. Mayo Clinic Proceedings. 2015; 90(5): 680-692. DOI: https://doi.org/10.1016/j.jpain.2016.03.001
  8. 11) Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang. A classification of chronic pain for ICD-11. Pain. 2015 Jun; 156(6): 1003-1007. DOI: https://doi.org/10.1097/j.pain.0000000000000160
  9. 12) Watson CP, Mackinnon SE, Dostrovsky JO, Bennet GJ, Farran RP, Carlson T. Nerve resection, crush and re-location relieve complex regional pain syndrome type II: a case report. Pain. 2014; 155(6): 1168-1173. DOI: https://doi.org/10.1016/j.pain.2014.01.025
  10. 13) Seminowicz DA, Wideman TH, Naso L, Hatami-Khoroushahi Z, Fallatah S, Ware MA, Jarzem P, Bushnell MC, Shir Y, Ouellet JA, Stone LS. Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J Neurosci. 2011; 31(20): 7540-7550. DOI: https://doi.org/10.1523/JNEUROSCI.5280-10.2011
  11. 14) Torrance N, Smith BH, Bennet MI, Lee AJ. The Epidemiology of Chronic Pain of Predominantly Neuropathic Origin. Results From a General Population Survey. J Pain. 2006; 7(4): 281-289. DOI: https://doi.org/10.1016/j.jpain.2005.11.008
  12. 15) Treede RD, Kenshalo DR, Gracely RH, Jones AKP. The cortical representation of pain. Pain. 1999; 79:105-111. DOI: https://doi.org/10.1016/S0304-3959(98)00184-5
  13. 16) Fein A. Nociception and the perception of pain. Creative Commons Attribution-Noncommercial-Share Alike 3.0 United States License. 17) Gemes G, Koopmeiners A, Rigaud M, Lirk P, Sapunar D, Bangaru ML, Vilceanu D, Garrison SR, Ljubkovic M, Mueller SJ, Stucky CL, Hogan QH. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury. J Physiol. 2013 Feb 15; 591(4): 1111-1131. 18) Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and Molecular Mechanisms of Pain. Cell. 2009 Oct 16; 139(2): 267-284. 19) Mense S, Gerwin RD. Muscle Pain: Understanding the Mechanisms. Springer-Verlag. 2010.
  14. 20) McDougall JJ. Arthritis and pain: Neurogenic origin of joint pain. Arthritis Res Ther. 2006: 8(6): 220. DOI: https://doi.org/10.1186/ar2069
  15. 21) Felson D. The sources of pain in knee osteoarthritis. Curr Opin Rheumatol. 2005; 17: 624-628. DOI: https://doi.org/10.1097/01.bor.0000172800.49120.97
  16. 22) Mantyh PW. The neurobiology of skeletal pain. Eur J Neurosci. 2014 Feb; 39(3): 508-519. DOI: https://doi.org/10.1111/ejn.12462
  17. • Robinson DR. Gebhart Gr. Inside information - 'The unique featur visceral sensation. Mol Interv. 2008: Oct: 8(5): 242-25 24) Bove GM. Epi-perineurial anatomy, innervation, and axonal nociceptive mechanisms. J Bodyw Mov Ther. 2008; 12(3):185-190. 25) Teixeira MJ, Almeida DB, Yeng LT. Concept of acute neuropathic pain. The role of nervi nervorum in the distinction between acute nociceptive and neuropathic pain. Rev Dor. São Paulo. 2016; 17 (Suppl 1): S5-S10.
  18. 5) Kim YS. Anderson M. Kyoungsook P. Zheng O. Agarwal A. Gor . Saulafu. Young L. He S. La Vinka PC. Zhou F. Bergles D. Hana
  19. M, Guan Y, Spray DC, Dong Z. Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain. Neuron. 2016; 91: 1085-1096. DOI: https://doi.org/10.1016/j.neuron.2016.07.044
  20. 27) Black JA, Hains BC, Dib-Hajj SD, Waxman SG. Voltage-gated sodium channels and pain associated with nerve injury and neuropathies. In Sodium Channels, Pain, and Analgesia, edited by Kevin Coward and Mark D. Baker, Birkhäuser Verlag Basel/ Switzerland. 2005: 1-21. DOI: https://doi.org/10.1007/3-7643-7411-X_1
  21. 28) Pintelon I, Brouns I, De Proost 1, Van Meir F, Timmermans JP, Adriaensen D. Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts. Am J Respir Cell Mol Biol. 2007; 36(5): 541-551. DOI: https://doi.org/10.1165/rcmb.2006-0256OC
  22. 29) Cooper BY, Vierck CJ, Yeomans DC. Selective reduction of second pain sensations by systemic morphine in humans. Pain. 1986, 24: 93-116. 30) Vierck CJ. Opioids: Effects od systemic morphine on evoked pain. In: Enciclopedic Reference of Pain. RF Schmidt and WD Willis (Eds). Springer-Verlag, Heidelberg. 2007: 2983-2988. DOI: https://doi.org/10.1016/0304-3959(86)90030-8
  23. 31) Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004; 28(2): 140-175. DOI: https://doi.org/10.1016/j.jpainsymman.2004.05.002
  24. 32) Varenna M. Bisphosphonates beyond their anti-osteoclastic properties. Rheumatology (Oxford). 2014; 53: 965-967. DOI: https://doi.org/10.1093/rheumatology/ket370
  25. 33) Mantyh PW. Bone Cancer Pain: From Mechanism to Therapy. Curr Opin Support Palliat Care. 2014 Jun; 8(2): 83-90. DOI: https://doi.org/10.1097/SPC.0000000000000048
  26. 34) Koewler NJ, Freeman KT, Buus RJ, Herrera MB, Jimenez-Andrade JM, Ghilardi JR, Peters CM, Sullivan LJ, Kuskowski MA, Lewis JL, Mantyh PW. Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur. JBMR. 2007; 22: 1732-1742. DOI: https://doi.org/10.1359/jbmr.070711
  27. 35) Lane NE, Silverman SL. Anabolic therapies. Current osteoporosis reports. 2010; 8: 23-27. DOI: https://doi.org/10.1007/s11914-010-0005-4
  28. 36) Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015; 16: 321. 37) Wesselmann U, Baranowski AP, Börjesson M, Curran NC, Czakanski PP, Giamberardino MA, Ness TJ, Robbins MT, Traub RJ. Emerging therapies and novel approaches to visceral pain. Drug Discov Today Ther Strateg. 2009; 6(3): 89-95. DOI: https://doi.org/10.1016/j.ddstr.2009.05.001
  29. 38) Belmonte C, Cervero E. Neurobiology of nociceptors. Oxford University Press. Oxford. 1996. DOI: https://doi.org/10.1093/acprof:oso/9780198523345.001.0001
  30. 39) Scheible HG. Peripheral and central mechanisms of pain generation. HEP. 2006: 177: 3-28. DOI: https://doi.org/10.1007/978-3-540-33823-9_1
  31. 40) Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010 Nov 1; 120(11): 3760-3772. DOI: https://doi.org/10.1172/JCI42843
  32. 41) Demartini L, Bonezzi C. All'origine del dolore. Ed. Momento Medico. 2017.
  33. 42) Buonocore M, Demartini L, Aloisi AM, Bonezzi C. Dynamic Mechanical Allodynia-One Clinical Sign, Several Mechanisms: Five Illustrative Cases. Pain Pract. 2016 Mar; 16(3): E48-E55. 43) Janig W, Levine JD, Michaelis M. Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma. In: Kumazawa T, Kruger L, Mizumura K (eds) The polymodal receptor: a gateway to pathological pain. Progress in brain research, vol 113. Elsevier Science, Amsterdam. 1996; 161-184. DOI: https://doi.org/10.1016/S0079-6123(08)61087-0
  34. 44) Devor M, De Koninck Y, Sommer C. Underlying Mechanisms of Neuropathic Pain: Refresher Courses, 15th World Congress on Pain Srinivasa N. Raja and Claudia L. Sommer, editors IASP Press, Washington, D.C. 2014.
  35. 45) Wu G, Ringkamp M, Hartke TV, Murinson BB, Campbell JN, Griffin W, Meyer RA. Early onset of spontaneous activity in uninjured Cfiber nociceptors after injury to neighbouring nerve fibers. J Neurosci. 2001; 21: 141-145. DOI: https://doi.org/10.1523/JNEUROSCI.21-08-j0002.2001
  36. 46) Zimmermann M. Pathobiology of neuropathic pain. EJP. 2001; 429: 23-37. DOI: https://doi.org/10.1016/S0014-2999(01)01303-6
  37. 47) Oaklander AL. Mechanisms of pain and itch caused by herpes zoster (shingles). J Pain. 2008 Jan; 9(1 Suppl 1): S10-S18. DOI: https://doi.org/10.1016/j.jpain.2007.10.003
  38. 48) Li CY, Song YH, Higuera ES, Luo ZD. Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci. 2004 Sep 29; 24(39): 8494-8499. DOI: https://doi.org/10.1523/JNEUROSCI.2982-04.2004
  39. 49) Woolf, CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983; 306: 686-688. DOI: https://doi.org/10.1038/306686a0
  40. 50) Obata K, Yamanaka H, Fukuoka T, Yi D, Tokunaga A, Hashimoto N, Yoshikawa H, Noguchi K. Contribution of injured and uninjured dorsal root ganglion neurons to pain behaviour and the changes in gene expression following chronic constriction injury of the sciatic nerve in rats. Pain. 2003; 101: 65-77. DOI: https://doi.org/10.1016/S0304-3959(02)00296-8

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