1. IntroductionThe redefinition of neuropathic pain,23 which specifically excludes the concept of “dysfunction,” has left a large group of patients without a valid pathophysiological descriptor for their experience of pain. This group comprises people who have neither obvious activation of nocicepto

Do we need a third mechanistic descriptor for chronic pain states

Summary Small fibre neuropathies are a heterogeneous group of disorders affecting thinly myelinated Aδ-fibres and unmyelinated C-fibres. Although multiple causes of small nerve fibre degeneration have been reported, including via genetic mutations, the cause of small fibre neuropathy remains unknown in up to 50% of cases. The typical clinical presentation of small fibre neuropathy is that of a symmetrical, length-dependent polyneuropathy associated with sensory or autonomic symptoms. More rarely, the clinical presentation is characterised by non-length-dependent, focal, or multifocal symptoms. The diagnostic tests to identify small fibre neuropathy include skin biopsy, quantitative sensory, and autonomic testing. Additional tests, such as those measuring small fibre-related evoked potentials and corneal confocal microscopy, might contribute to a better understanding of these neuropathies. Biochemical markers can also help in screening patients for the presence of small fibre neuropathy and to assess disease progression.

The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes

Summary Neuropathic pain—pain caused by a lesion or disease of the somatosensory nervous system—is underdiagnosed and difficult to treat. However, development of easy-to-use questionnaires based mainly on self-reports of symptoms has improved diagnosis and management. Two types of questionnaires (screening and assessment) have been validated, and rapidly translated and revalidated in several languages, probably because of their simplicity. Screening questionnaires help clinicians to identify neuropathic pain easily, particularly in patients with complex medical conditions (eg, spinal cord injury). Their use in large-scale epidemiological studies has provided estimates of the prevalence of neuropathic pain and identified risk factors for neuropathic pain in the general population and in disorders such as diabetes. Assessment questionnaires measure neuropathic symptoms and have been used to create phenotypic profiles of patients in various neuropathic conditions. These profiles can predict treatment outcomes, and thus enable a personalised therapeutic approach. The dissemination of these questionnaires in different countries should further improve diagnosis and management worldwide and advance knowledge on the mechanisms of neuropathic pain.

Diagnosis and assessment of neuropathic pain through questionnaires

Chemotherapy-induced peripheral neuropathy (CIPN) is a major challenge, with increasing impact as oncological treatments, using potentially neurotoxic chemotherapy, improve cancer cure and survival. Acute CIPN occurs during chemotherapy, sometimes requiring dose reduction or cessation, impacting on survival. Around 30% of patients will still have CIPN a year, or more, after finishing chemotherapy. Accurate assessment is essential to improve knowledge around prevalence and incidence of CIPN. Consensus is needed to standardize assessment and diagnosis, with use of well-validated tools, such as the EORTC-CIPN 20. Detailed phenotyping of the clinical syndrome moves toward a precision medicine approach, to individualize treatment. Understanding significant risk factors and pre-existing vulnerability may be used to improve strategies for CIPN prevention, or to use targeted treatment for established CIPN. No preventive therapies have shown significant clinical efficacy, although there are promising novel agents such as histone deacetylase 6 (HDAC6) inhibitors, currently in early phase clinical trials for cancer treatment. Drug repurposing, eg, metformin, may offer an alternative therapeutic avenue. Established treatment for painful CIPN is limited. Following recommendations for general neuropathic pain is logical, but evidence for agents such as gabapentinoids and amitriptyline is weak. The only agent currently recommended by the American Society of Clinical Oncology is duloxetine. Mechanisms are complex with changes in ion channels (sodium, potassium, and calcium), transient receptor potential channels, mitochondrial dysfunction, and immune cell interactions. Improved understanding is essential to advance CIPN management. On a positive note, there are many potential sites for modulation, with novel analgesic approaches.

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Chemotherapy-induced peripheral neuropathy: where are we now?

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations (vol 156, pg 2337, 2015)

The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses.

Classification algorithm for the International Classification of Diseases-11 chronic pain classification: development and results from a preliminary pilot evaluation.

REPRINTED WITH PERMISSION OF IASP: Pain 2015 (156) 6: 1003-1008. A classification of chronic pain for ICD-11

The EQ-5D and Short Form (SF)12 are widely used generic health-related quality of life (HRQoL) question

Blair H. Smith

Papers

Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations (vol 156, pg 2337, 2015)

Classification algorithm for the International Classification of Diseases-11 chronic pain classification: development and results from a preliminary pilot evaluation.

REPRINTED WITH PERMISSION OF IASP: Pain 2015 (156) 6: 1003-1008. A classification of chronic pain for ICD-11

3 Estimating the burden of disease in chronic pain with and without 4 neuropathic characteristics: Does the choice between the EQ-5D