Semin Neurol 2016; 36(05): 462-468
DOI: 10.1055/s-0036-1584950
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neuropathic Pain

Janne Gierthmühlen
1   Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
Ralf Baron
1   Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
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23. September 2016 (online)


Diagnosing neuropathic pain and distinguishing it from nociceptive pain can be challenging, but is essential because both forms of pain require different treatment strategies. The diagnosis of neuropathic pain is primarily based on clinical findings. Therefore, a careful, focused history and an examination of the signs characteristic of neuropathic pain are crucial. Imaging techniques and electrophysiological examinations, as well as punch skin biopsy can support the clinical diagnosis. Ideally, treatment should be individualized using a mechanism-based approach. However, current treatments are usually dispensed without precision, and calcium-channel-acting modulators (pregabalin, gabapentin), tricyclic antidepressants, and serotonin-noradrenalin reuptake inhibitors (duloxetine, venlafaxine) represent first-line treatment options for neuropathic pain. Although neurostimulation techniques for the treatment of refractory chronic pain have become more important, most evidence of long-term effectiveness and safety is still limited, which strengthens the need for larger randomized controlled trials before final recommendations can be made.

  • References

  • 1 Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9 (8) 807-819
  • 2 Rolke R, Baron R, Maier C , et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006; 123 (3) 231-243
  • 3 Fields HL, Rowbotham M, Baron R. Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis 1998; 5 (4) 209-227
  • 4 Dworkin RH, Turk DC, Peirce-Sandner S , et al. Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations. Pain 2010; 149 (2) 177-193
  • 5 Devor M. Pathophysiology of nerve injury. In: Cervero F, Jensen TS, eds. Pain. Amsterdam: Elsevier BV; 2006: 261-276
  • 6 Noguchi K. Central sensitization following nerve injury: molecular mechanisms. In: Cervero F, Jensen TS, eds. Pain. Amsterdam: Elsevier BV; 2006: 277-291
  • 7 Puretić MB, Demarin V. Neuroplasticity mechanisms in the pathophysiology of chronic pain. Acta Clin Croat 2012; 51 (3) 425-429
  • 8 Watkins LR, Maier SF. Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 2002; 82 (4) 981-1011
  • 9 Ludwig J, Baron R. Complex regional pain syndrome: an inflammatory pain condition?. Drug Discov Today Dis Mech 2004; 1 (4) 449-455
  • 10 Gierthmühlen J, Binder A, Baron R. Mechanism-based treatment in complex regional pain syndromes. Nat Rev Neurol 2014; 10 (9) 518-528
  • 11 Handwerker HO. Nociceptors: neurogenic inflammation. In: Cervero F, Jensen TS, eds. Pain. Amsterdam: Elsevier BV; 2006: 23-33
  • 12 Lee MC, Zambreanu L, Menon DK, Tracey I. Identifying brain activity specifically related to the maintenance and perceptual consequence of central sensitization in humans. J Neurosci 2008; 28 (45) 11642-11649
  • 13 Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152 (3, Suppl) S2-S15
  • 14 Baron R, Hans G, Dickenson AH. Peripheral input and its importance for central sensitization. Ann Neurol 2013; 74 (5) 630-636
  • 15 LaMotte RH, Shain CN, Simone DA, Tsai EF. Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. J Neurophysiol 1991; 66 (1) 190-211
  • 16 Torebjörk HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol 1992; 448: 765-780
  • 17 Koltzenburg M, Torebjörk HE, Wahren LK. Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain 1994; 117 (Pt 3): 579-591
  • 18 Ziegler EA, Magerl W, Meyer RA, Treede RD. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain 1999; L; 122 (Pt 12): 2245-2257
  • 19 Magerl W, Wilk SH, Treede RD. Secondary hyperalgesia and perceptual wind-up following intradermal injection of capsaicin in humans. Pain 1998; 74 (2–3) 257-268
  • 20 Gottrup H, Kristensen AD, Bach FW, Jensen TS. Aftersensations in experimental and clinical hypersensitivity. Pain 2003; 103 (1–2) 57-64
  • 21 Sarkar S, Woolf CJ, Hobson AR, Thompson DG, Aziz Q. Perceptual wind-up in the human oesophagus is enhanced by central sensitisation. Gut 2006; 55 (7) 920-925
  • 22 Juhl GI, Jensen TS, Norholt SE, Svensson P. Central sensitization phenomena after third molar surgery: a quantitative sensory testing study. Eur J Pain 2008; 12 (1) 116-127
  • 23 Herrero JF, Laird JM, López-García JA. Wind-up of spinal cord neurones and pain sensation: much ado about something?. Prog Neurobiol 2000; 61 (2) 169-203
  • 24 Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992; 38 (4) 397-421
  • 25 Treede RD, Handwerker HO, Baumgärtner U, Meyer RA, Magerl W. Hyperalgesia and allodynia: taxonomy, assessment, and mechanisms. In: Brune K, Handwerker HO, eds. Hyperalgesia: Molecular Mechanisms and Clinical Implications. Seattle, WA: IASP Press; 2004: 1-15
  • 26 Baron R. Mechanisms of disease: neuropathic pain—a clinical perspective. Nat Clin Pract Neurol 2006; 2 (2) 95-106
  • 27 Finnerup NB, Attal N, Haroutounian S , et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14 (2) 162-173
  • 28 Dworkin RH, O'Connor AB, Audette J , et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010; 85 (3, Suppl) S3-S14
  • 29 Deer TR, Mekhail N, Provenzano D , et al; Neuromodulation Appropriateness Consensus Committee. 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 2014; 17 (6) 515-550 , discussion 550
  • 30 Papuć E, Rejdak K. The role of neurostimulation in the treatment of neuropathic pain. Ann Agric Environ Med 2013; 1 (Special issue 1): 14-17
  • 31 Wolter T. Spinal cord stimulation for neuropathic pain: current perspectives. J Pain Res 2014; 7: 651-663
  • 32 Forget P, Boyer T, Steyaert A, Masquelier E, Deumens R, Le Polain de Waroux B. Clinical evidence for dorsal root ganglion stimulation in the treatment of chronic neuropathic pain. A review. Acta Anaesthesiol Belg 2015; 66 (2) 37-41
  • 33 Lefaucheur JP. Cortical neurostimulation for neuropathic pain: state of the art and perspectives. Pain 2016; 157 (Suppl. 01) S81-S89