Neuropathic Pain: Redefinition and a grading system for clinical and research purposes

Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany.
Neurology (Impact Factor: 8.29). 05/2008; 70(18):1630-5. DOI: 10.1212/01.wnl.0000282763.29778.59
Source: PubMed


Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.

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Available from: Jonathan O Dostrovsky, Feb 02, 2015
    • "Neuropathic pain is commonly accompanied by sensory abnormalities such as hypoesthesia, hyperesthesia, or allodynia . 3,4 Recently, we have reported a strong association between self-reported symptoms of altered sensory function and the presence and intensity of PPSP. 5 A grading system, classifying pain as " possible " , " probable " , and " definite " neuropathic pain was proposed by Treede et al. in 2008. 6 Pain may be of possible neuropathic origin if pain distribution is neuroanatomically plausible and the patient's history suggests a relevant lesion or disease affecting the peripheral or central somatosensory system. "
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    ABSTRACT: Background: The contribution of nerve lesions and neuropathic pain to persistent post-surgical pain (PPSP) is poorly established. The aim of this study was to assess the association between PPSP and symptoms and signs of possible nerve injury in an unselected surgical sample. Methods: Eighty-one individuals with and without persistent pain after surgical procedures, were recruited from a cross-sectional study. Follow-up examination with questionnaires and quantitative sensory testing was performed 15-32 months later (21-64 months after surgery). Results: The median rating of maximum pain intensity among individuals with PPSP decreased from numerical rating scale 4/10 at baseline to 2/10 at follow-up, but considerable changes occurred in both directions. Individuals with PPSP at follow-up were significantly more likely to self-report sensory abnormalities than those without PPSP; however, results from sensory testing did not differ significantly between the groups. Self-report of sensory disturbances at the site of surgery was associated with increased warm detection thresholds and tactile pain thresholds. Among individuals with PPSP, 61% had positive findings on sensory testing, suggesting probable neuropathic pain. Conclusion: In this study, associations between self-reported symptoms and PPSP were stronger than associations between self-reported symptoms and results of psychophysical tests. Fluctuations in pain intensity together with wide ranges for normal variability in sensory functions, hampers detection of significant group differences. Methodological aspects of quantitative sensory testing applied in a mixed clinical sample are discussed.
    No preview · Article · Nov 2015 · Acta Anaesthesiologica Scandinavica
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    • "Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system (Treede et al., 2008). Voltage-gated sodium channel have a major role in the generation and conduction of the electrical pain information in the central and peripheral nervous system (Dib-Hajj et al., 2010; Catterall, 2012). "
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    ABSTRACT: Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. In a previous study, we evaluated the analgesic activity of sumatriptan, an agonist of serotonin 5HT1B/D receptors, and some new chiral bioisosteres, using the hot plate test in the mouse. Interestingly, we observed that the analgesic effectiveness was not necessarily correlated to serotonin agonism. In this study, we evaluated whether sumatriptan and its congeners may inhibit heterologously expressed hNav1.7 sodium channels using the patch-clamp method. We show that sumatriptan blocks hNav1.7 channels only at very high, supratherapeutic concentrations. In contrast, its three analogs, namely 20b, (R)-31b, and (S)-22b, exert a dose and use-dependent sodium channel block. At 0.1 and 10 Hz stimulation frequencies, the most potent compound, (S)-22b, was 4.4 and 1.7 fold more potent than the well-known sodium channel blocker mexiletine. The compound induces a negative shift of voltage dependence of fast inactivation, suggesting higher affinity to the inactivated channel. Accordingly, we show that (S)-22b likely binds the conserved local anesthetic receptor within voltage-gated sodium channels. Combining these results with the previous ones, we hypothesize that use-dependent sodium channel blockade contributes to the analgesic activity of (R)-31b and (S)-22b. These later compounds represent promising lead compounds for the development of efficient analgesics, the mechanism of action of which may include a dual action on sodium channels and 5HT1D receptors.
    Full-text · Article · Aug 2015 · Frontiers in Pharmacology
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    • "Pathological pain, including neuropathic pain and fibromyalgia, is a frequent condition and is very challenging to manage. Neuropathic pain is described as " pain arising as a direct consequence of a lesion or disease affecting the somatosensory system " (Treede et al., 2008). The definition and causes of fibromyalgia are vague. "
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    ABSTRACT: Antidepressant drugs of the SSRI family are used as a third-line treatment for neuropathic pain. In contrast MAOi antidepressants, that also increase extracellular serotonin bioavailability have little or no effects on this condition. In addition to their action of the serotonin transporter, some SSRI have been shown to inhibit voltage gated sodium channels. Here we investigated the potential inhibition of SSRIs and MAOi antidepressants on Nav1.7 or Nav1.8, which are expressed in sensory neurons and play an important role in pain sensation. We used the whole-cell patch-clamp technique on HEK293 cells expressing either Nav1.7 or Nav1.8, and evaluated the effects of the SSRIs fluoxetine, paroxetine, and citalopram as well as one MAOi antidepressants on the electrophysiological properties of the Na(+) channels. Paroxetine exhibited the greatest affinity for Na(+) channels. In ascending order of affinity for Nav1.7 were paroxetine (IC50=10µM), followed by fluoxetine (IC50=66µM), then citalopram (IC50=174µM). In ascending order of affinity for Nav1.8 were paroxetine (IC50=9µM), followed by fluoxetine (IC50=49µM), then citalopram (IC50=100µM). Paroxetine and fluoxetine accelerated the onset of slow-inactivation and delayed the time-course of recovery from inactivation for both channels. Paroxetine and fluoxetine also had a prominent effect on the frequency-dependent inhibition, with a greater effect on Nav1.7. In contrast to SSRIs, MAOi did not affect Na(+) channels currents. These results suggest that, in certain conditions, the analgesic effect of SSRIs may in part be due to their interactions with Na(+) channels. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · European journal of pharmacology
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