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.
The traditional translational approach in neuropathic pain research has mainly consisted to date in translating basic findings from animal models of nerve injury to the clinic. Because of the ...difficulty to extrapolate mechanisms from animals to humans, an inverse translational approach ("top-down") has been advocated and contributed to the development of therapy. In particular, a number of treatments such as neurostimulation techniques have been initially assessed in patients and then translated to animal models for further investigation of their mechanisms. Therapeutic approaches based on an in-depth assessment of sensory phenotypes, suggestive of mechanisms, have also been implemented. The biggest trend in recent translational research is to investigate mechanisms or predict therapeutic response in patients by integrating multimodal approaches. The present narrative review emphasizes these various aspects of translational research in neuropathic pain.
Our aim was to estimate the prevalence of distal chronic pain with neuropathic characteristics in patients with type 1 and type 2 diabetes mellitus and its impact on quality of life, mood, anxiety, ...sleep and healthcare utilization.
In total, 885 patients were screened and 766 diabetic patients (38.7% with type 1 diabetes mellitus, 44.8% women, mean age: 57.2 ± 14.9 years) were enrolled consecutively over a three-month period in this observational study by 85 diabetes specialists working in a hospital department or in private practice. All the patients completed a series of questionnaires for the detection of chronic pain (i.e. daily pain for more than three months) in the lower limbs and assessment of health-related quality of life (Medical Outcomes Short Form 12 scale), sleep disturbances (MOS sleep scale), depression and anxiety (Hospital Anxiety and Depression scale). Patients with chronic pain were also assessed with the 7-item DN4-interview questionnaire, the monofilament test and the Michigan Neuropathy Screening Instrument (MNSI).
The overall prevalence of chronic pain with neuropathic characteristics was 20.3% 95% CI 17.4-23.1. The MNSI examination score suggested that pain was related to polyneuropathy, in 80.1% of these patients (89.5% of those with bilateral pain). Patients with chronic pain had a poorer quality of life and more sleep disturbances, anxiety and depression than patients without pain and the presence of neuropathic characteristics was predictive of such impairments. Only 38.6% of the patients had received appropriate treatment for neuropathic pain.
Chronic pain with neuropathic characteristics concerns one in five diabetic patients, has a significant impact on quality of life and is not adequately managed. The close correlation between the DN4 questionnaire and MNSI results suggests that screening tools for neuropathic pain could be used in daily practice for the identification of painful diabetic polyneuropathy.
The redefinition of neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system," which was suggested by the International Association for the ...Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the "definite" level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.
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.
Although coronavirus disease 2019 (COVID-19) most commonly manifests with acute respiratory symptoms, one very common symptom of COVID-19 is pain. As COVID-19 often causes peripheral or central ...neurological complications, it is anticipated that a number of the chronic pain complications of COVID-19 will be neuropathic. This review first examines the most common viral infections responsible for neurological complications including neuropathic pain. These encompass herpes zoster, HIV, poliovirus, enteroviruses, and several tropical viruses. Neurological complications of COVID-19 including in particular Guillain-Barré syndrome, myelitis, and stroke are reviewed with regards to their potential risk of chronic neuropathic pain. Prospective longitudinal cohorts of patients should be implemented to evaluate the exact risk of neuropathic pain after COVID-19.
This nationwide survey of the French general population indicates that pain with neuropathic characteristics induces a specific disease burden as compared to nonneuropathic pain.
We report the first ...nationwide survey of the impact of neuropathic pain, as opposed to nonneuropathic pain, on quality of life and health care utilization in the French general population. A postal questionnaire was sent to a representative sample of 4554 respondents from an initial nationwide survey of 30,155 subjects with or without chronic pain. It included pain characteristics (Neuropathic Pain Symptom Inventory, DN4), quality of life (Medical Outcomes Short Form 12, SF-12), sleep, anxiety/depressive symptoms (Hospital Anxiety and Depression Scale) and health care utilization. In total, 3899 (85.6%) questionnaires were returned, 3816 (97.9%) could be assessed and 3165 subjects (82.9%) confirmed their pain status. Subjects reporting pain and neuropathic characteristics based on the DN4 displayed a higher degree of impairment of all dimensions relating to quality of life and sleep and had higher anxiety/depression scores than those reporting pain without neuropathic characteristics and those without pain (
P
<
.01). They also made greater use of health care facilities, particularly as concerned neurological treatments and visits to neurologists (21% vs 9%;
P
<
.01). Multivariate analyses showed that the neuropathic characteristics of pain made an independent contribution to quality-of-life impairment (
P
<
.0001 and
P
=
.0005 for the physical and mental scores of the SF-12 respectively). Our study indicates that the disease burden of chronic pain depends on the nature of the pain, independently of its intensity and duration.
Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat neuropathic pain but the quality of evidence remains low. We aimed to assess the efficacy and safety of neuronavigated ...rTMS to the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in neuropathic pain over 25 weeks. We carried out a randomized double-blind, placebo-controlled trial at four outpatient clinics in France. Patients aged 18-75 years with peripheral neuropathic pain were randomly assigned at a 1:1 ratio to M1 or DLPFC-rTMS and rerandomized at a 2:1 ratio to active or sham-rTMS (10 Hz, 3000 pulses/session, 15 sessions over 22 weeks). Patients and investigators were blind to treatment allocation. The primary end point was the comparison between active M1-rTMS, active DLPCF-rTMS and sham-rTMS for the change over the course of 25 weeks (Group × Time interaction) in average pain intensity (from 0 no pain to 10 maximal pain) on the Brief Pain Inventory, using a mixed model repeated measures analysis in patients who received at least one rTMS session (modified intention-to-treat population). Secondary outcomes included other measures of pain intensity and relief, sensory and affective dimensions of pain, quality of pain, self-reported pain intensity and fatigue (patients diary), Patient and Clinician Global Impression of Change (PGIC, CGIC), quality of life, sleep, mood and catastrophizing. This study is registered with ClinicalTrials.gov NCT02010281. A total of 152 patients were randomized and 149 received treatment (49 for M1; 52 for DLPFC; 48 for sham). M1-rTMS reduced pain intensity versus sham-rTMS (estimate for Group × Session interaction: -0.048 ± 0.02; 95% CI: -0.09 to -0.01; P = 0.01). DLPFC-rTMS was not better than sham (estimate: -0.003 ± 0.01; 95% CI: -0.04 to 0.03, P = 0.9). M1-rRMS, but not DLPFC-rTMS, was also superior to sham-rTMS on pain relief, sensory dimension of pain, self-reported pain intensity and fatigue, PGIC and CGIC. There were no effects on quality of pain, mood, sleep and quality of life as all groups improved similarly over time. Headache was the most common side effect and occurred in 17 (34.7%), 23 (44.2%) and 13 (27.1%) patients from M1, DLPFC and sham groups, respectively (P = 0.2). Our results support the clinical relevance of M1-rTMS, but not of DLPFC-rTMS, for peripheral neuropathic pain with an excellent safety profile.
The goal of this study was to develop and validate a self-completed questionnaire, the Fibromyalgia Rapid Screening Tool (FiRST), for the detection of fibromyalgia syndrome in patients with diffuse ...chronic pain. Items requiring “yes/no” responses and relating to the most relevant clinical characteristics of fibromyalgia were compiled by a group of rheumatologists and pain experts. The provisional questionnaire was tested in a prospective multicenter study of 162 patients with chronic pain due to fibromyalgia (according to ACR criteria) (
n
=
92) compared with a group of patients with chronic diffuse pain due to other rheumatic conditions, including rheumatoid arthritis (
n
=
32), ankylosing spondylitis (
n
=
25) and osteoarthritis (
n
=
13). Identification of the most discriminant combinations of items for fibromyalgia and the calculation of their sensitivity and specificity were based on both univariate and multivariate (stepwise logistic regression) analyses. The assessment of the psychometric properties of the questionnaire also dealt with face validity, content validity, test–retest reliability and convergent/divergent validity. Based on univariate and multivariate analyses, we retained only six items in the final version of FiRST. These items were used to calculate the sensitivity, specificity and predictive accuracy of the questionnaire. A cut-off score of 5 (corresponding to the number of positive items) gave the highest rate of correct identification of patients (87.9%), with a sensitivity of 90.5% and a specificity of 85.7%. In conclusion, FiRST is a brief, simple and straightforward self-administered questionnaire with excellent discriminative value, of potential value for the detection of fibromyalgia in both daily practice and clinical research.
The potentially serious nature of herpes zoster (HZ) and the long-term complication post-herpetic neuralgia (PHN) are often underestimated. One in four people will contract herpes zoster in their ...lifetime, with this risk rising markedly after the age of 50 years, and affecting one in two in elderly individuals. Pain is the predominant symptom in all phases of HZ disease, being reported by up to 90% of patients. In the acute phase, pain is usually moderate or severe, with patients ranking HZ pain as more intense than post-surgical or labour pains. Up to 20% of patients with HZ develop PHN, which is moderate-to-severe chronic pain persisting for months or years after the acute phase. We review the available data on the effect of HZ and PHN on patients' quality-of-life.
Findings show that HZ, and particularly PHN, have a major impact on patients' lives across all four health domains--physical, psychological, functional and social. There is a clear correlation between increasing severity of pain and greater interference with daily activities. Non-pain complications such as HZ ophthalmicus can increase the risk of permanent physical impairment. Some elderly individuals may experience a permanent loss of independence after an acute episode of HZ. Current challenges in the management of HZ and PHN are highlighted, including the difficulty in administering antiviral agents before pain becomes established and the limited efficacy of pain treatments in many patients. We discuss the clinical rationale for the HZ vaccine and evidence demonstrating that the vaccine reduces the burden of the disease. The Shingles Prevention Study, conducted among >38,000 people aged >or=60 years old, showed that the HZ vaccine significantly reduces the burden of illness and the incidence of both HZ and PHN. In the entire study population, zoster vaccination reduced the severity of interference of HZ and PHN with activities of daily living by two-thirds, as measured by two questionnaires specific to HZ.
A vaccination scheme may positively impact the incidence and course of HZ disease, thereby improving patients' quality-of-life.
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