Neuropathic Pain

  • Gerald W. Grass


Few medical problems are more complex in nature and perplexing to effectively manage than pain. Pain, in its acute form, is necessary for survival and serves an important role in the way an organism interfaces with its environment by signaling real or impending harm. Occasionally, circumstances lead to activity in the pain-signaling pathway that is not beneficial to the organism and has no survival value. Injury to nerve fibers or their projections may cause conditions that are not usually perceived as painful to become excessively painful. Although most nerve injuries do not lead to clinically important and sustained pain, in some cases, even small degrees of insult can precipitate severe and unremitting pain. Neuropathic pain exists when a nerve responds to an injury in a typical fashion and then continues to respond and signal pain long after the injurious stimulus is removed.


Spinal Cord Injury Neuropathic Pain Carpal Tunnel Syndrome Trigeminal Neuralgia Complex Regional Pain Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Allen SC. Neuropathic pain – the case for opioid therapy. Oncology 2008;74(suppl 1):76–82.PubMedCrossRefGoogle Scholar
  2. Argoff CE, Backonja MM, Belgrade MJ, et al. Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain. Mayo Clin Proc. 2006;81(4 suppl):S12–25.PubMedGoogle Scholar
  3. Artus M, Croft P, Lewis M. The use of CAM and conventional treatments among primary care consulters with chronic musculoskeletal pain. BMC Fam Pract. 2007;8:26.PubMedCrossRefGoogle Scholar
  4. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349(20):1943–53.PubMedCrossRefGoogle Scholar
  5. Baron R. Peripheral neuropathic pain: from mechanisms to symptoms. Clin J Pain. 2000;16(2 suppl):S12–20.PubMedGoogle Scholar
  6. Bennett MI, Attal N, Backonja MM, et al. Using screening tools to identify neuropathic pain. Pain 2007;127(3):199–203.PubMedCrossRefGoogle Scholar
  7. Besson JM. The neurobiology of pain. Lancet 1999;353(9164):1610–5.PubMedCrossRefGoogle Scholar
  8. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008;136(3):380–7.Google Scholar
  9. Brodner RA, Taub A. Chronic pain exacerbated by long-term narcotic use in patients with nonmalignant disease: clinical syndrome and treatment. Mt Sinai J Med. 1978;45(2):233–7.PubMedGoogle Scholar
  10. Campbell CM, Edwards RR, Carmona C, et al. Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain. Pain 2009;141(1–2):114–8.Google Scholar
  11. Carpenter JS, Sloan P. Andrykowski MA, et al. Risk factors for pain after mastectomy/lumpectomy. Cancer Pract. 1999;7(2):66–70.PubMedCrossRefGoogle Scholar
  12. Challapalli V, Tremont-Lukats IW, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. 2005(4):CD003345.Google Scholar
  13. Cherry CL, Skolasky RL, Lal L, et al. Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort. Neurology 2006;66(6):867–73.PubMedCrossRefGoogle Scholar
  14. Coyle DE. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia 1998;23(1):75–83.PubMedCrossRefGoogle Scholar
  15. Cummins TR, Sheets PL, Waxman SG. The roles of sodium channels in nociception: implications for mechanisms of pain. Pain 2007;131(3):243–57.PubMedCrossRefGoogle Scholar
  16. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132(3):237–51.PubMedCrossRefGoogle Scholar
  17. Eisenberg E, McNicol ED, Carr DB. Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials. JAMA 2005;293(24):3043–52.PubMedCrossRefGoogle Scholar
  18. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States. 1990–1997: results of a follow-up national survey. JAMA 1998;280(18):1569–75.PubMedCrossRefGoogle Scholar
  19. Evans S, Fishman B, Spielman L, Haley A. Randomized trial of cognitive behavior therapy versus supportive psychotherapy for HIV-related peripheral neuropathic pain. Psychosomatics 2003;44(1):44–50.PubMedCrossRefGoogle Scholar
  20. Farrar JT, Young JP, Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94(2):149–58.PubMedCrossRefGoogle Scholar
  21. Finnerup NB, Otto M, Jensen TS, Sindrup SH. An evidence-based algorithm for the treatment of neuropathic pain. MedGenMed 2007;9(2):36.PubMedGoogle Scholar
  22. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005;118(3):289–305.PubMedCrossRefGoogle Scholar
  23. Gilron I, Bailey JM. Trends in opioid use for chronic neuropathic pain: a survey of patients pursuing enrollment in clinical trials. Can J Anaesth. 2003;50(1):42–7.PubMedCrossRefGoogle Scholar
  24. Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352(13):1324–34.PubMedCrossRefGoogle Scholar
  25. Gagnon B, Almahrezi A, Schreier G. Methadone in the treatment of neuropathic pain. Pain Res Manage. 2003;8(3):149–54.Google Scholar
  26. Gilron I. Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Curr Opin Anaesthesiol. 2007;20(5):456–72.PubMedCrossRefGoogle Scholar
  27. Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ 2006;175(3):265–75.PubMedGoogle Scholar
  28. Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology 2003;60(6):927–34.PubMedGoogle Scholar
  29. Guldiken S, Guldiken B, Arikan E, Altun Ugur B, Kara M, Tugrul A. Complete relief of pain in acute painful diabetic neuropathy of rapid glycaemic control (insulin neuritis) with venlafaxine HCL. Diabetes Nutr Metab. 2004;17(4):247–9.PubMedGoogle Scholar
  30. Gustorff B, Dorner T, Likar R, et al. Prevalence of self-reported neuropathic pain and impact on quality of life: a prospective representative survey. Acta Anaesthesiol Scand. 2008;52(1):132–6.PubMedCrossRefGoogle Scholar
  31. Hains BC, Waxman SG. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J Neurosci. 2006;26(16):4308–17.PubMedCrossRefGoogle Scholar
  32. Kim H, Dionne RA. Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans. Mol Pain 2007;3:6.PubMedCrossRefGoogle Scholar
  33. Maguire MF, Ravenscroft A, Beggs D, Duffy JP. A questionnaire study investigating the prevalence of the neuropathic component of chronic pain after thoracic surgery. Eur J Cardiothorac Surg. 2006;29(5):800–5.PubMedCrossRefGoogle Scholar
  34. Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol. 1994;4(2):69–82.PubMedCrossRefGoogle Scholar
  35. Matthews EA, Bee LA, Stephens GJ, Dickenson AH. The Cav2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain. Eur J Neurosci. 2007;25(12):3561–9.PubMedCrossRefGoogle Scholar
  36. Meier T, Wasner G, Faust M, et al. Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study. Pain 2003;106(1–2):151–8.PubMedCrossRefGoogle Scholar
  37. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150(699):971–9.PubMedCrossRefGoogle Scholar
  38. Mersky H, Bogduk N. ed. Classification of chronic pain. Seattle, WA: IASP Press; 1994. pp. 209–14.Google Scholar
  39. Meyler WJ, de Jongste MJ, Rolf CA. Clinical evaluation of pain treatment with electrostimulation: a study on TENS in patients with different pain syndromes. Clin J Pain 1994;10(1):22–7.PubMedCrossRefGoogle Scholar
  40. Morgello S, Estanislao L, Simpson D, et al. HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank. Arch Neurol. 2004;61(4):546–51.PubMedCrossRefGoogle Scholar
  41. Morley JS, Bridson J, Nash TP, Miles JB, White S, Makin MK. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med. 2003;17(7):576–87.PubMedCrossRefGoogle Scholar
  42. Morley S, Keefe FJ. Getting a handle on process and change in CBT for chronic pain. Pain 2007;127(3):197–8.PubMedCrossRefGoogle Scholar
  43. Moulin DE, Palma D, Watling C, Schulz V. Methadone in the management of intractable neuropathic noncancer pain. Can J Neurol Sci. 2005;32(3):340–3.PubMedGoogle Scholar
  44. Osterberg A, Boivie J, Thuomas KA. Central pain in multiple sclerosis – prevalence and clinical characteristics. Eur J Pain. 2005;9(5):531–42.PubMedCrossRefGoogle Scholar
  45. Pace MC, Mazzariello L, Passavanti MB, Sansone P, Barbarisi M, Aurilio C. Neurobiology of pain. J Cell Physiol. 2006;209(1):8–12.PubMedCrossRefGoogle Scholar
  46. Pasero C. Pathophysiology of neuropathic pain. Pain Manage Nurs. 2004;5(4 suppl 1):3–8.CrossRefGoogle Scholar
  47. Poobalan AS, Bruce J, King PM, Chambers WA, Krukowski ZH, Smith WC. Chronic pain and quality of life following open inguinal hernia repair. Br J Surg. 2001;88(8):1122–6.PubMedCrossRefGoogle Scholar
  48. Poobalan AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA. A review of chronic pain after inguinal herniorrhaphy. Clin J Pain. 2003;19(1):48–54.PubMedCrossRefGoogle Scholar
  49. Portenoy RK, Rapscak S, Kanner R. Tricyclic antidepressants in chronic pain. Pain 1984;18(2):213–5.PubMedCrossRefGoogle Scholar
  50. Raja SN, Haythornthwaite JA, Pappagallo M, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002;59(7):1015–21.PubMedGoogle Scholar
  51. Simpson DM, Kitch D, Evans SR, et al. HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology 2006;66(11):1679–87.PubMedCrossRefGoogle Scholar
  52. Sindrup SH and Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999;83(3):389–400.PubMedCrossRefGoogle Scholar
  53. Stacey BR. Management of peripheral neuropathic pain. Am J Phys Med Rehabil. 2005;84(3 suppl):S4–16.PubMedGoogle Scholar
  54. Tegeder I, Costigan M, Griffin RS, et al. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med. 2006;12(11):1269–77.PubMedCrossRefGoogle Scholar
  55. Terayama R, Omura S, Fujisawa N, Yamaai T, Ichikawa H, Sugimoto T. Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury. Neuroscience 2008;153(4):1245–55.PubMedCrossRefGoogle Scholar
  56. Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70(18):1630–5.PubMedCrossRefGoogle Scholar
  57. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006;7(4):281–9.PubMedCrossRefGoogle Scholar
  58. Turk DC, Swanson KS, Tunks ER. Psychological approaches in the treatment of chronic pain patients – when pills, scalpels, and needles are not enough. Can J Psychiatry. 2008;53(4):213–23.PubMedGoogle Scholar
  59. Ultenius C, Linderoth B, Meyerson BA, Wallin J. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat. Neurosci Lett. 2006;399(1–2):85–90.PubMedCrossRefGoogle Scholar
  60. Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and treatment options. Pain Med. 2008;9(6):660–74.PubMedCrossRefGoogle Scholar
  61. Vadivelu N, Schreck M, Lopez J, Kodumudi G, Narayan D. Pain after mastectomy and breast reconstruction. Am Surg. 2008;74(4):285–96.PubMedGoogle Scholar
  62. Watson CP, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998;50(6):1837–41.PubMedGoogle Scholar
  63. Watson CP, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain 2003;105(1–2):71–8.PubMedCrossRefGoogle Scholar
  64. Waxman SG. Neurobiology: a channel sets the gain on pain. Nature 2006;444(7121):831–2.PubMedCrossRefGoogle Scholar
  65. Waxman SG, Cummins TR, Dib-Hajj SD, Black JA. Voltage-gated sodium channels and the molecular pathogenesis of pain: a review. J Rehabil Res Dev. 2000;37(5):517–28.PubMedGoogle Scholar
  66. Wilson JA, Garry EM, Anderson HA, et al. NMDA receptor antagonist treatment at the time of nerve injury prevents injury-induced changes in spinal NR1 and NR2B subunit expression and increases the sensitivity of residual pain behaviours to subsequently administered NMDA receptor antagonists. Pain 2005;117(3):421–32.PubMedCrossRefGoogle Scholar
  67. Yucel A, Ozyalcin S, Koknel Talu G, et al. The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study. Eur J Pain. 2005;9(4):407–16.PubMedCrossRefGoogle Scholar
  68. Zhao P, Waxman SG, Hains BC. Extracellular signal-regulated kinase-regulated microglia-neuron signaling by prostaglandin E2 contributes to pain after spinal cord injury. J Neurosci. 2007;27(9):2357–68.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gerald W. Grass
    • 1
    • 2
  1. 1.Yale University School of MedicineNew HavenUSA
  2. 2.VA Connecticut Healthcare SystemNew HavenUSA

Personalised recommendations