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Journal ArticleDOI

Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus.

TL;DR: Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients as discussed by the authors, which has not gained a large acceptance among clinicians for many reasons, and in significant part because of the lack of information about standards for performing QST, its potential utility and interpretation of results.
Abstract: Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients. Although QST shares similarities with the quantitative assessment of hearing or vision, which is extensively used in clinical practice and research, it has not gained a large acceptance among clinicians for many reasons, and in significant part because of the lack of information about standards for performing QST, its potential utility, and interpretation of results. A consensus meeting was convened by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) to formulate recommendations for conducting QST in clinical practice and research. Research studies have confirmed the utility of QST for the assessment and monitoring of somatosensory deficits, particularly in diabetic and small fiber neuropathies; the assessment of evoked pains (mechanical and thermal allodynia or hyperalgesia); and the diagnosis of sensory neuropathies. Promising applications include the assessment of evoked pains in large-scale clinical trials and the study of conditioned pain modulation. In clinical practice, we recommend the use QST for screening for small and large fiber neuropathies; monitoring of somatosensory deficits; and monitoring of evoked pains, allodynia, and hyperalgesia. QST is not recommended as a stand-alone test for the diagnosis of neuropathic pain. For the conduct of QST in healthy subjects and in patients, we recommend use of predefined standardized stimuli and instructions, validated algorithms of testing, and reference values corrected for anatomical site, age, and gender. Interpretation of results should always take into account the clinical context, and patients with language and cognitive difficulties, anxiety, or litigation should not be considered eligible for QST. When appropriate standards, as discussed here, are applied, QST can provide important and unique information about the functional status of somatosensory system, which would be complementary to already existing clinical methods.
Citations
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Journal ArticleDOI
TL;DR: Better understanding of allodynia and hyperalgesia might provide clues to the underlying pathophysiology of neuropathic pain and, as such, they represent new or additional endpoints in pain trials.
Abstract: Summary Allodynia (pain due to a stimulus that does not usually provoke pain) and hyperalgesia (increased pain from a stimulus that usually provokes pain) are prominent symptoms in patients with neuropathic pain. Both are seen in various peripheral neuropathies and central pain disorders, and affect 15–50% of patients with neuropathic pain. Allodynia and hyperalgesia are classified according to the sensory modality (touch, pressure, pinprick, cold, and heat) that is used to elicit the sensation. Peripheral sensitisation and maladaptive central changes contribute to the generation and maintenance of these reactions, with separate mechanisms in different subtypes of allodynia and hyperalgesia. Pain intensity and relief are important measures in clinical pain studies, but might be insufficient to capture the complexity of the pain experience. Better understanding of allodynia and hyperalgesia might provide clues to the underlying pathophysiology of neuropathic pain and, as such, they represent new or additional endpoints in pain trials.

551 citations

Journal ArticleDOI
19 Aug 2017-Pain
TL;DR: A new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles is presented, which may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.
Abstract: Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.

407 citations

Journal ArticleDOI
01 Sep 2016-Pain
TL;DR: Evidence is presented on the most promising phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics.
Abstract: There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice This has led to calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain

244 citations


Cites background from "Value of quantitative sensory testi..."

  • ...Quantitative sensory testing has been used for decades in a variety of research settings, often for the purpose of diagnosing and monitoring sensory neuropathies and pain disorders, as well as for the investigation of pain mechanisms, the characterization of somatosensory profiles in various pain disorders, and the elucidation of individual differences in pain sensitivity and pain modulation.(4,15,15,62,161,190,203,204) Quantita-...

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  • ...clinical deterioration (eg, the development of foot ulcers in patients with diabetes) or the worsening of neuropathy.(15) To date, relatively few phase 2 and 3 analgesic RCTs have used baseline phenotyping by QST to predict treatment response....

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  • ...Recent reviews have called for increased application and study of such brief, bedside QST protocols, which do not require specialized equipment, and which may be feasible additions to large multicenter trials.(15,27,62) In addition, trial-to-trial variability of...

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Journal ArticleDOI
TL;DR: Although evidence suggests that QST may be useful in a mechanism-based classification of pain, there are gaps in current understanding that need to be addressed including making QST more applicable in clinical settings.
Abstract: Objective This review summarizes the scientific literature relating to the use of quantitative sensory testing (QST) for mechanism-based pain management.

219 citations

Journal ArticleDOI
TL;DR: This article provides a contemporary review of the acute effects of exercise on pain and pain sensitivity, including in people with chronic pain conditions, and discusses possible biological mechanisms and potential influence of sex and psychosocial factors.

217 citations

References
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Journal ArticleDOI
TL;DR: A grading system of definite, probable, and possible neuropathic pain is proposed, which includes the grade possible, which can only be regarded as a working hypothesis, and the grades probable and definite, which require confirmatory evidence from a neurologic examination.
Abstract: 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.

2,342 citations


"Value of quantitative sensory testi..." refers background in this paper

  • ...The diagnosis of neuropathic pain is based on the combination of clinical symptoms (pain and positive sensory phenomena) and signs (sensory deficits and evoked pains) [105]....

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Journal ArticleDOI
01 Aug 2006-Pain
TL;DR: Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes as well as judge plus or minus signs in patients.
Abstract: The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

2,030 citations

Journal ArticleDOI
TL;DR: A comprehensive QST protocol is compiled using well established tests for nearly all aspects of somatosensation to test for patterns of sensory loss or gain, and to assess both cutaneous and deep pain sensitivity.

1,147 citations


"Value of quantitative sensory testi..." refers background or methods in this paper

  • ...Description In the last 2 decades, several groups have published normative data sets for thermal threshold detection and pain threshold testing, with various algorithms used [22,29,76,93,94,109,113,114]....

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  • ...The instructions should be concise and to the point, as well as clear and short in terms of wording so subjects can easily remember the instructions for the duration of the QST [93,94]....

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  • ...For subjects, a set of training stimuli are generally used in an unaffected area before testing on the same day (clinical use) or, if possible, 1 to 2 days before (research use) in order to familiarize the subject with the stimulus administration and response procedures [93,94,109]....

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  • ...Most commonly, computerized systems are used to deliver thermal stimuli, while handheld devices are generally used for application of mechanical and vibratory stimuli [10,21,94] (Appendix A)....

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  • ...QST instructions are generally prepared in standardized written form and presented verbally; they are written in such a way as to avoid influencing subjects’ expectations—for example, by not telling them what they should or should not feel [93,94]....

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Journal ArticleDOI
TL;DR: These findings suggest that the pathophysiology of migraine involves not only irritation of meningeal perivascular pain fibers but also a transient increase in the responsiveness of central pain neurons that process information arising from intracranial structures and skin.
Abstract: Recent animal studies on the mechanism of migraine show that intracranial pain is accompanied by increased periorbital skin sensitivity. These findings suggest that the pathophysiology of migraine involves not only irritation of meningeal perivascular pain fibers but also a transient increase in the responsiveness (ie, sensitization) of central pain neurons that process information arising from intracranial structures and skin. The purpose of this study was to determine whether the increased skin sensitivity observed in animal also develops in humans during migraine attacks. Repeated measurements of mechanical and thermal pain thresholds of periorbital and forearm skin areas in the absence of, and during, migraine attacks enabled us to determine the occurrence of cutaneous allodynia during migraine. Cutaneous allodynia is pain resulting from a nonnoxious stimulus to normal skin. In 79% of the patients, migraine was associated with cutaneous allodynia as defined, and in 21% of the patients it was not. The cutaneous allodynia occurred either solely within the referred pain area on the ipsilateral head, or within and outside the ipsilateral head. Cutaneous allodynia in certain well-defined regions of the skin during migraine is an as yet unreported neurological finding that points to hyperexcitability of a specific central pain pathway that subserves intracranial sensation.

926 citations


"Value of quantitative sensory testi..." refers background or methods in this paper

  • ...QST has largely contributed to characterize allodynia and hyperalgesia to brush and to static mechanical or thermal stimuli in neuropathic syndromes, particularly postherpetic neuralgia, painful polyneuropathies, and central pain [11,25,28,39,56,77, 84,88,95], as well as in other pain disorders, such as headache, fibromyalgia, osteoarthritis, migraine, and orofacial pain [9,14,18,19,40,63,66,101,103,108] (Table 5)....

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  • ...This may contribute to characterize various painful conditions; for Table 1 Differences and similarities between quantitative sensory testing and conventional electro Characteristic Electrophysiological techniques: NCS and SEP [24,31] Type of information obtained Functional status of large myelinated sensory fiber system terms of conduction, velocity and size of the amplitude, refl status of myelination and fiber loss Localization along neuroaxis, of entire length for SEP and P NCS No ability to assess positive phenomena Do not assess small fibers and spinothalamic tract Nature of the subject participation in the testing Does not require responses from the subject No active cooperation required Need for training Training required for investigators but not for subjects Normative data Published normative data and available data from most e physiological laboratories NCS, nerve conduction studies; SEP, somatosensory-evoked potential. example, brush-induced allodynia is frequent in traumatic nerve lesions or postherpetic neuralgia [77,95], mechanical static hyperalgesia is common in complex regional pain syndrome, fibromyalgia, or osteoarthritis [63,72,77,102], and hyperalgesia to cold stimuli is a hallmark of oxaliplatin-induced neuropathy [7,77]....

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  • ...Painful and painless neuropathic patients [ NP and NNP in patients [52] Suggestive of mechanisms [18,19,26,39] Longitudinal studies...

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  • ...One retrospective study assessed the relationship between individual outcomes of bedside sensory examination and thermal and Table 4 Clinical utility of QST to assess sensory deficits in research studies and consensus recomm Deficit Evidence from research studies Diabetic neuropathy (thermal, mechanical, vibration) Documentation of sensory deficits Cold deficits: 27–98% sensitivitya [21] Warm deficits: 22–88% sensitivitya [21] Vibration: 58–84% sensitivity, 51–86% specificity [ Early impairment of thermal testing [74,119] Correlation with the clinical staging of neurop [29,74,88,119] Moderate correlation with NCS [19,42,61,78,92] Longitudinal studies Monitoring of sensory function [30,37,64,98,120] Response to disease modifying agentsb [3,4,120] Prediction of clinical deterioration [38,44] Small fiber neuropathies (thermal testing) Sensitivity 36–100% but criteria of small fiber neuropathy var [20,27,117] to skin punch biopsy (62–88%)c [27] Diagnostic value Lower diagnostic efficiency (47...

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  • ...Correlation with the clinical staging of neurop [29,74,88,119] Moderate correlation with NCS [19,42,61,78,92] Longitudinal studies Monitoring of sensory function [30,37,64,98,120] Response to disease modifying agents [3,4,120] Prediction of clinical deterioration [38,44]...

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Journal ArticleDOI
01 Jan 2011-Pain
TL;DR: Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes and quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes.
Abstract: This is a revision of guidelines, originally published in 2004, for the assessment of patients with neuropathic pain. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level. Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes. Clinical examination, including accurate sensory examination, is the basis of neuropathic pain diagnosis. For more accurate sensory profiling, quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes. Measurement of trigeminal reflexes mediated by A-beta fibers can be used to differentiate symptomatic trigeminal neuralgia from classical trigeminal neuralgia. Measurement of laser-evoked potentials is useful for assessing function of the A-delta fiber pathways in patients with neuropathic pain. Functional brain imaging is not currently useful for individual patients in clinical practice, but is an interesting research tool. Skin biopsy to measure the intraepidermal nerve fiber density should be performed in patients with clinical signs of small fiber dysfunction. The intensity of pain and treatment effect (both in clinic and trials) should be assessed with numerical rating scale or visual analog scale. For future neuropathic pain trials, pain relief scales, patient and clinician global impression of change, the proportion of responders (50% and 30% pain relief), validated neuropathic pain quality measures and assessment of sleep, mood, functional capacity and quality of life are recommended.

909 citations


"Value of quantitative sensory testi..." refers background or methods in this paper

  • ...Several studies have reported that the presence and severity of allodynia to brush could discriminate patients with a painful neurological lesion from those without pain [26,28,39,91] or with nonneuropathic pain [52]....

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  • ...Response to analgesic treatments [6,52] Prediction of the response to therapy [6,17 Prediction of postsurgical pain [15,49,79]...

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  • ...This is despite the existence of published guidelines and recommendations for the diagnosis and follow-up of sensory abnormalities in diabetic neuropathy using QST [23,59,99] and for the assessment of neuropathic pain [25,52]....

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  • ...In particular, mechanical and thermal QST has been extensively used in double-blind pharmacological clinical trials conducted by single centers (see [52] for references) and has been able to reveal antihyperalgesic properties of various drugs (eg, iv sodium channel blockers, NMDA antagonists)....

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  • ...QST has sometimes revealed modality-specific effects on distinct subtypes of hyperalgesia (ie, thermal vs mechanical allodynia, predominant effects on enhanced temporal summation) [52]....

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