Nadine Attal

Bio: Nadine Attal is an academic researcher from Université Paris-Saclay. The author has contributed to research in topics: Neuropathic pain & Chronic pain. The author has an hindex of 5, co-authored 14 publications receiving 398 citations. Previous affiliations of Nadine Attal include CHU Ambroise Paré.

The IASP classification of chronic pain for ICD-11: chronic neuropathic pain.

Abstract: The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.

Pharmacotherapyofneuropathicpain:whichdrugs, which treatment algorithms?

Abstract: Neuropathic pain (NP) is a significant medical and socioeconomic burden. Epidemiological surveys have indicated that many patients with NP do not receive appropriate treatment for their pain. A number of pharmacological agents have been found to be effective in NP on the basis of randomized controlled trials including, in particular, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor antidepressants, pregabalin, gabapentin, opioids, lidocaine patches, and capsaicin highconcentration patches. Evidence-based recommendations for the pharmacotherapy of NP have recently been updated. However, meta-analyses indicate that only a minority of patients with NP have an adequate response to drug therapy. Several reasons may account for these findings, including a modest efficacy of the active drugs, a high placebo response, the heterogeneity of diagnostic criteria for NP, and an inadequate classification of patients in clinical trials. Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms.

Quantitative sensory testing using DFNS protocol in Europe: an evaluation of heterogeneity across multiple centers in patients with peripheral neuropathic pain and healthy subjects.

Abstract: Quantitative sensory testing (QST) in accordance with the DFNS (German Research Network on Neuropathic Pain) protocol assesses the function of afferent nerve fibers on the basis of 13 parameters. Within the consortia IMI (Innovative Medicines Initiative) Europain and Neuropain, QST results from pain research units experienced in QST across Europe can be compared for the first time. Aim of this analysis was to identify possible biases in the QST assessment between 10 centers from 8 different European countries. In total, 188 healthy subjects, 217 patients with painful polyneuropathy, and 150 patients with painful peripheral nerve injury were included in the analysis. Mixed effects models were constructed for each of the 11 normally distributed QST parameters with z-value as the dependent variable, and center as the random effect. The I statistic for heterogeneity was calculated, an index ranging from 0% (no heterogeneity) to 100% (perfect heterogeneity). Data from healthy subjects were comparable with the existing reference data base. Patients with polyneuropathy mainly displayed loss of sensory function, whereas patients with peripheral nerve injury often showed sensory loss combined with mechanical hyperalgesia. Heterogeneity was overall low between different centers and parameters. There was no systematic heterogeneity for patients with painful peripheral nerve injury and painful polyneuropathy. For healthy subjects, only blunt pressure pain threshold showed a considerable heterogeneity of 42% (95% confidence interval: 0%-66%). In conclusion, QST of both healthy subjects and patients with peripheral neuropathic pain is largely homogenous within the European centers, an essential prerequisite for performing multicenter QST-based studies.

Assessment of spinal somatosensory systems with diffusion tensor imaging in syringomyelia

Abstract: OBJECTIVE: We tested the use of diffusion tensor imaging with three-dimensional fiber tracking (DTI-FT) for the assessment of spinal sensory tract lesions. We systematically examined the relationships between tract lesions quantified with DTI-FT, and somatosensory dysfunction assessed with quantitative sensory testing (QST) and laser evoked potentials (LEP), in patients with syringomyelia. METHODS: We studied 28 patients with cervical syringomyelia and thermosensory impairment of the hands, and 19 healthy volunteers. We performed a DTI-FT of the spinal cord focusing on the upper segment (C3-C4) of the syrinx. Three-dimensional DTI-FT parameters (i.e. fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the full, anterior and posterior spinal cord were individually compared to QST (i.e. thermal detection thresholds) and LEP (i.e. amplitude, latency and spinothalamic tract (STT) conduction time) of the hands. RESULTS: Patients had a significantly lower FA, but not ADC, than healthy subjects. Mean FA of the full section of the spinal cord was related both to sensory deficits (i.e. increase of warm (rho = -0.63, p<0.010) and cold thresholds (rho = -0.72;p< 0.001 of the hands) and to changes in LEP parameters, in particular STT conduction time (rho = -0.75;p<0.010). Correlations between FA and the clinical and electrophysiological measurements were higher in the anterior area (where the STT is confined) than in the posterior area of the spinal cord. CONCLUSIONS: These data indicate that diffusion tensor imaging with 3D-fiber tracking is a new imaging method which is suitable for the objective and quantitative anatomical assessment of spinal somatosensory system dysfunction.

Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11).

Abstract: Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperation with the WHO, an IASP Working Group has developed a classification system that is applicable in a wide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in our proposal, we call this subgroup "chronic primary pain." In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as "chronic secondary pain" where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right.

The IASP classification of chronic pain for ICD-11: Chronic primary pain

Abstract: This article describes a proposal for the new diagnosis of chronic primary pain (CPP) in ICD-11. Chronic primary pain is chosen when pain has persisted for more than 3 months and is associated with significant emotional distress and/or functional disability, and the pain is not better accounted for by another condition. As with all pain, the article assumes a biopsychosocial framework for understanding CPP, which means all subtypes of the diagnosis are considered to be multifactorial in nature, with biological, psychological, and social factors contributing to each. Unlike the perspectives found in DSM-5 and ICD-10, the diagnosis of CPP is considered to be appropriate independently of identified biological or psychological contributors, unless another diagnosis would better account for the presenting symptoms. Such other diagnoses are called "chronic secondary pain" where pain may at least initially be conceived as a symptom secondary to an underlying disease. The goal here is to create a classification that is useful in both primary care and specialized pain management settings for the development of individualized management plans, and to assist both clinicians and researchers by providing a more accurate description of each diagnostic category.

Neuropathic Pain: From Mechanisms to Treatment

Abstract: Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia, and central poststroke pain Most patients complain of an ongoing or intermittent spontaneous pain of, for example, burning, pricking, squeezing quality, which may be accompanied by evoked pain, particular to light touch and cold Ectopic activity in, for example, nerve-end neuroma, compressed nerves or nerve roots, dorsal root ganglia, and the thalamus may in different conditions underlie the spontaneous pain Evoked pain may spread to neighboring areas, and the underlying pathophysiology involves peripheral and central sensitization Maladaptive structural changes and a number of cell-cell interactions and molecular signaling underlie the sensitization of nociceptive pathways These include alteration in ion channels, activation of immune cells, glial-derived mediators, and epigenetic regulation The major classes of therapeutics include drugs acting on α2δ subunits of calcium channels, sodium channels, and descending modulatory inhibitory pathways

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

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.