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  • Review Article
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Reappraising neuropathic pain in humans—how symptoms help disclose mechanisms

Nature Reviews Neurology volume 9, pages 572–582 (2013)Cite this article

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Abstract

Neuropathic pain—that is, pain arising directly from a lesion or disease that affects the somatosensory system—is a common clinical problem, and typically causes patients intense distress. Patients with neuropathic pain have sensory abnormalities on clinical examination and experience pain of diverse types, some spontaneous and others provoked. Spontaneous pain typically manifests as ongoing burning pain or paroxysmal electric shock-like sensations. Provoked pain includes pain induced by various stimuli or even gentle brushing (dynamic mechanical allodynia). Recent clinical and neurophysiological studies suggest that the various pain types arise through distinct pathophysiological mechanisms. Ongoing burning pain primarily reflects spontaneous hyperactivity in nociceptive-fibre pathways, originating from 'irritable' nociceptors, regenerating nerve sprouts or denervated central neurons. Paroxysmal sensations can be caused by several mechanisms; for example, electric shock-like sensations probably arise from high-frequency bursts generated in demyelinated non-nociceptive Aβ fibres. Most human and animal findings suggest that brush-evoked allodynia originates from Aβ fibres projecting onto previously sensitized nociceptive neurons in the dorsal horn, with additional contributions from plastic changes in the brainstem and thalamus. Here, we propose that the emerging mechanism-based approach to the study of neuropathic pain might aid the tailoring of therapy to the individual patient, and could be useful for drug development.

Key Points

  • Clinical symptoms of neuropathic pain can arise through various pathophysiological mechanisms, which has implications for diagnosis and treatment

  • The most common neuropathic pain is ongoing burning pain, which reflects spontaneous hyperactivity in nociceptive-fibre pathways originating from 'irritable' nociceptors, regenerating sprouts or denervated central neurons

  • In patients with burning pain, the clinical sensory deficit is less severe for 'irritable' nociceptors, and more severe in the case of denervated central neurons; sensory deficit without pain probably implies functional deafferentation

  • Electric shock-like paroxysmal sensations probably arise through high-frequency ectopic bursts generated in demyelinated, non-nociceptive Aβ fibres

  • Mechanical dynamic allodynia is mediated by non-nociceptive Aβ fibres that activate central pain pathways; in peripheral neuropathies, sensitized C-nociceptors probably also contribute to maintenance of allodynia and to central sensitization

  • Sensory examination and neurophysiological techniques help to identify patients at high risk of allodynia; in peripheral and central pain syndromes, risk of allodynia increases if thermal-pain pathways are partially preserved

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Figure 1: Laboratory testing in patients with neuropathic pain.
Figure 2: Models for ongoing burning pain in primary sensory neuron disease.
Figure 3: Correlations between neurophysiological abnormalities and pain.18,20,22

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Authors and Affiliations

  1. Department of Neurology and Psychiatry, Sapienza University, Viale Università 30, Rome, 00185, Italy

    Andrea Truini & Giorgio Cruccu

  2. Central Integration of Pain (NeuroPain-CRNL), INSERM and Claude Bernard University of Lyon, Hôpital Neurologique, 59 Boulevard Pinel, Lyon, 69677, Bron, France

    Luis Garcia-Larrea

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  1. Andrea Truini
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All authors researched data for the article, and made substantial contributions to discussion of the content, writing, and to review and/or editing of the manuscript before submission.

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Correspondence to Giorgio Cruccu.

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Truini, A., Garcia-Larrea, L. & Cruccu, G. Reappraising neuropathic pain in humans—how symptoms help disclose mechanisms. Nat Rev Neurol 9, 572–582 (2013). https://doi.org/10.1038/nrneurol.2013.180

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