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Pain Mechanisms in Patients with Chronic Pain

Clinical Drug Investigation volume 32, pages 45–52 (2012)Cite this article

Abstract

The mechanisms involved in the development of chronic pain are varied and complex. Pain processes are plastic and unrelieved pain may lead to changes in the neural structure involved in pain generation. Nociceptive pain announces the presence of a potentially damaging stimulus that occurs when noxious stimuli activate primary afferent neurons. Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system resulting from trauma, infection, ischaemia, cancer or other causes such as chemotherapy. The exact mechanisms involved in the pathophysiology of chronic pain are not well understood, but rapid and long-term changes are thought to occur in parts of the central nervous system that are involved in the transmission and modulation of pain following injury. Peripheral and central sensitization of sensory nerve fibres are the primary reasons for hypersensitivity to pain after injury, and mainly occur in inflammatory and neuropathic pain. During these processes the sensation of pain is enhanced as a result of changes in the environment, the nerve fibres and modifications of the functional properties and the genetic programme of primary and secondary afferent neurons. Non-steroidal anti-inflammatory drugs and opioid analgesics are two of the most common classes of drugs used for the treatment of pain. Response to drug treatment shows significant interindividual variability and can lead to side effects. The neurobiological mechanisms that cause pain may account for the different types of pain observed. Identification of these mechanisms may allow us to move from an empirical therapeutic approach to one that it is specifically targeted at the particular mechanisms of the type of pain experienced by an individual patient.

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References

  1. Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965; 150(3699): 971–9

    Article  CAS  PubMed  Google Scholar 

  2. Walsh NE, Dumitru D, Schoenfeld LS, et al. Treatment of the Patient with Chronic Pain. In: DeLisa JA, Gans BM, Walsh NE, Bockenek WL, Frontera WR, Geringer SR, et al., editors. Physical Medicine & Rehabilitation: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins; 2005: 497–8

    Google Scholar 

  3. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004; 140(6): 441–51

    PubMed  Google Scholar 

  4. Malik B, Stillman M. Pain Syndromes. In: Savitz S, Ronthal M, editors. Neurology Review for Psychiatrists. 1st Edition ed. Philadelphia: Lippincott Williams & Wilkins; 2009: 253–5

    Google Scholar 

  5. Koltzenburg M, Scadding J. Neuropathic pain. Curr Opin Neurol 2001; 14(5): 641–7

    Article  CAS  PubMed  Google Scholar 

  6. Improvement. IfCS. Health care guideline: Assessment and management of acute pain. 2008 [updated 2008; cited 13 September 2011]; Available from: http://www.icsi.org/pain_acute/pain__acute__assessment_and_management_of__3.html

  7. Kidd BL, Urban LA. Mechanisms of inflammatory pain. Br J Anaesth 2001; 87(1): 3–11

    Article  CAS  PubMed  Google Scholar 

  8. Nicholson B. Responsible prescribing of opioids for the management of chronic pain. Drugs 2003; 63(1): 17–32

    Article  PubMed  Google Scholar 

  9. Schaible HG, Richter F. Pathophysiology of pain. Langenbecks Arch Surg 2004; 389(4): 237–43

    Article  PubMed  Google Scholar 

  10. Stucky CL, Gold MS, Zhang X. Mechanisms of pain. Proc Natl Acad Sci U S A 2001; 98(21): 11845–6

    Article  CAS  PubMed  Google Scholar 

  11. Dickenson AH. The roles of transmitters and their receptors in systems related to pain and analgesia. In: Max M, editor. Pain. Seattle: International Association for the Study of Pain Press, 1999: 381

    Google Scholar 

  12. Heller PH, Green PG, Tanner KD, et al. Peripheral Neural Contributions to Inflammation. In: Fields HL, Liebeskind JC, editors. Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues. Seattle: International Association for the Study of Pain Press, 1994: 31–3

    Google Scholar 

  13. Wilcox GL. Pharmacology of pain and analgesia. In: Max M, editor. Pain, an updated review. Seattle: International Association for the Study of Pain, 1999; 573

    Google Scholar 

  14. Wood S. Anatomy and physiology of pain. 2008 [updated 2008; cited 15 September 2011]; Available from: http://www.nursingtimes.net/nursing-practice/1860931.article

  15. Farquhar-Smith W. Anatomy, physiology and pharmacology of pain. Anaesth Intensive Care Med 2008; 9(1): 3–7

    Article  Google Scholar 

  16. Ko S, Zhuo M. Central plasticity and persistent pain. Drug Discovery Today Dis Mod 2004; 1: 101–6

    Article  Google Scholar 

  17. Curatolo M, Arendt-Nielsen L, Petersen-Felix S. Central hypersensitivity in chronic pain: mechanisms and clinical implications. Phys Med Rehabil Clin N Am 2006; 17(2): 287–302

    Article  PubMed  Google Scholar 

  18. Rang HP, Bevan S, Dray A. Chemical activation of nociceptive peripheral neurones. Br Med Bull 1991; 47(3): 534–48

    CAS  PubMed  Google Scholar 

  19. Siddall PJ, Cousins MJ. Spinal pain mechanisms. Spine (Phila Pa 1976) 1997; 22(1): 98–104

    Article  CAS  Google Scholar 

  20. Ong CK, Lirk P, Tan CH, et al. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin Med Res 2007; 5(1): 19–34

    Article  CAS  PubMed  Google Scholar 

  21. Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2005; 64(5): 669–81

    Article  CAS  PubMed  Google Scholar 

  22. Scott PA, Kingsley GH, Smith CM, et al. Non-steroidal antiinflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials. Ann Rheum Dis 2007; 66(10): 1296–304

    Article  CAS  PubMed  Google Scholar 

  23. Trescot AM, Datta S, Lee M, et al. Opioid pharmacology. Pain Physician 2008; 11 (2 Suppl.): S133–53

    PubMed  Google Scholar 

  24. Savage SR, Horvath R. Opioid Therapy of Pain. In: Ries RK, Fiellin DA, Miller SC, Saitz R, editors. Principles of Addiction Medication. Philadelphia: Lippincott Williams & Wilkins, 2009: 1330–2

    Google Scholar 

  25. Cherny N, Ripamonti C, Pereira J, et al. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol 2001; 19(9): 2542–54

    CAS  PubMed  Google Scholar 

  26. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the Food and Drug Administration, 1998–2005. Arch Intern Med 2007; 167(16): 1752–9

    Article  PubMed  Google Scholar 

  27. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279(15): 1200–5

    Article  CAS  PubMed  Google Scholar 

  28. Lee C, Morton CC. Structural genomic variation and personalized medicine. N Engl J Med 2008; 358(7): 740–1

    Article  CAS  PubMed  Google Scholar 

  29. Eckhardt K, Li S, Ammon S, et al. Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation. Pain 1998; 76(1–2): 27–33

    Article  CAS  PubMed  Google Scholar 

  30. Mikus G, Weiss J. Influence of CYP2D6 genetics on opioid kinetics, metabolism and response. Curr Pharmacogenom 2005; 3(1): 43–52

    Article  CAS  Google Scholar 

  31. Stamer UM, Musshoff F, Kobilay M, et al. Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin Pharmacol Ther 2007; 82(1): 41–7

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Università degli Studi di Milano and CNR-Institute of Neuroscience, Via Vanvitelli 32, 20129, Milano, Italy

    Diego Fornasari

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  1. Diego Fornasari
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Correspondence to Diego Fornasari.

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Fornasari, D. Pain Mechanisms in Patients with Chronic Pain. Clin Drug Investig 32, 45–52 (2012). https://doi.org/10.2165/11630070-000000000-00000

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  • DOI: https://doi.org/10.2165/11630070-000000000-00000

Keywords

  • Chronic Pain
  • Neuropathic Pain
  • Tramadol
  • Dorsal Horn
  • Oxycodone