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.

Neuropathic pain Redefinition and a grading system for clinical and research purposes

Sex, Gender, and Pain: A Review of Recent Clinical and Experimental Findings

Objective: Nociceptive and neuropathic components both contribute to pain. Since these components require different pain management strategies, correct pain diagnosis before and during treatment is highly desirable. As low back pain (LBP) patients constitute an important subgroup of chronic pain patients, we addressed the following issues: (i) to establish a simple, validated screening tool to detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to determine the prevalence of neuropathic pain components in LBP in a large-scale survey, and (iii) to determine whether LBP patients with an NeP component suffer from worse, or different, co-morbidities.Methods: In co-operation with the German Research Network on Neuropathic Pain we developed and validated the painDETECT questionnaire (PD‐Q) in a prospective, multicentre study and subsequently applied it to approximately 8000 LBP patients.Results: The PD‐Q is a reliable screening tool with high sensitivity, specificity and positive pred...

https://informahealthcare.com/doi/pdf/10.1185/030079906x132488

painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain

We conducted a large nationwide postal survey to estimate the prevalence of chronic pain with or without neuropathic characteristics in the French general population. A questionnaire aimed at identifying chronic pain (defined as daily pain for at least 3 months), evaluating its intensity, duration and body locations, was sent to a representative sample of 30,155 subjects. The DN4 questionnaire was used to identify neuropathic characteristics. Of the questionnaires, 24,497 (81.2%) were returned and 23,712 (96.8%) could be assessed. Seven thousand five hundred and twenty-two respondents reported chronic pain (prevalence=31.7%; [95%CI: 31.1-32.3]) and 4709 said the pain intensity was moderate to severe (prevalence=19.9%; [95%CI: 19.5-20.4]). Neuropathic characteristics were reported by 1631 respondents with chronic pain (prevalence=6.9%; [95%CI: 6.6-7.2]), which was moderate to severe in 1209 (prevalence=5.1% [95%CI: 4.8-5.4]). A higher prevalence of chronic pain with neuropathic characteristics was associated with middle age (50-64 years), manual professions and those living in rural areas. It was more frequently located in the lower limbs and its intensity and duration were higher in comparison with chronic pain without neuropathic characteristics. This large national population-based study indicates that a significant proportion of chronic pain patients report neuropathic characteristics. We identified distinctive socio-demographic profile and clinical features indicating that chronic pain with neuropathic characteristics is a specific health problem.

/pdf/prevalence-of-chronic-pain-with-neuropathic-characteristics-1sscp7ap0z.pdf

Prevalence of chronic pain with neuropathic characteristics in the general population

Most patients with neuropathic pain symptoms present and are managed in primary care, with only a minority being referred for specialist clinical assessment and diagnoses. Previous reviews have focused mainly on specific neuropathic pain conditions based in specialist settings. This is the first systematic review of epidemiological studies of neuropathic pain in the general population. Electronic databases were searched from January 1966 to December 2012, and studies were included where the main focus was on neuropathic pain prevalence and/or incidence, either as part of a specific neuropathic pain-related condition or as a global entity in the general population. We excluded studies in which data were extracted from pain or other specialist clinics or focusing on specific population subgroups. Twenty-one articles were identified and underwent quality assessment and data extraction. Included studies differed in 3 main ways: method of data retrieval, case ascertainment tool used, and presentation of prevalence/incidence rates. This heterogeneity precluded any meta-analysis. We categorised comparable incidence and prevalence rates into 2 main subgroups: (1) chronic pain with neuropathic characteristics (range 3–17%), and (2) neuropathic pain associated with a specific condition, including postherpetic neuralgia (3.9–42.0/100,000 person–years [PY]), trigeminal neuralgia (12.6–28.9/100,000 PY), painful diabetic peripheral neuropathy (15.3–72.3/100,000 PY), glossopharyngeal neuralgia (0.2–0.4/100,000 PY). These differences highlight the importance of a standardised approach for identifying neuropathic pain in future epidemiological studies. A best estimate of population prevalence of pain with neuropathic characteristics is likely to lie between 6.9% and 10%.

/pdf/neuropathic-pain-in-the-general-population-a-systematic-y9gq8optf0.pdf

Neuropathic pain in the general population: A systematic review of epidemiological studies

Few studies have directly compared the clinical features of neuropathic and non-neuropathic pains. For this purpose, the French Neuropathic Pain Group developed a clinician-administered questionnaire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination. This questionnaire was used in a prospective study of 160 patients presenting with pain associated with a definite neurological or somatic lesion. The most common aetiologies of nervous lesions (n=89) were traumatic nerve injury, post herpetic neuralgia and post stroke pain. Non-neurological lesions (n=71) were represented by osteoarthritis, inflammatory arthropathies and mechanical low back pain. Each patient was seen independently by two experts in order to confirm the diagnosis of neuropathic or non-neuropathic pain. The prevalence of pain descriptors and sensory dysfunctions were systematically compared in the two groups of patients. The analysis of the psychometric properties of the DN4 questionnaire included: face validity, inter-rater reliability, factor analysis and logistic regression to identify the discriminant properties of items or combinations of items for the diagnosis of neuropathic pain. We found that a relatively small number of items are sufficient to discriminate neuropathic pain. The 10-item questionnaire developed in the present study constitutes a new diagnostic instrument, which might be helpful both in clinical research and daily practice.

http://www.meduniwien.ac.at/phd-iai/fileadmin/ISMED/Literaturhinweise/Bouhassira_DN4-Pain_2005_114.pdf

Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4)

Parmi les douleurs du cancer qui echappent aux traitements medicaux, certaines sont particulierement difficiles a traiter en raison de leur localisation ou de leur extension comme les douleurs craniofaciales, les douleurs cervico-brachiales ou les douleurs osseuses diffuses. La decouverte des recepteurs aux opiaces en 1973 et la confirmation de l’efficacite antalgique des injections intra-thecales de morphine ont permis le developpement de l’analgesie intrathecale qui s’est imposee comme un des premiers traitements neurochirurgicaux de la douleur des cancers ne remontant pas au-dessus de la region cervicale [1]. L’injection directe de morphine dans le LCS a proximite des recepteurs specifiques permet de diminuer fortement les doses en evitant l’obstacle de la barriere hemato-encephalique, les limitations dues a l’absorption intestinale et au metabolisme de la drogue, tout en obtenant une meilleure efficacite et moins d’effets secondaires [2–4]. En 1982, Leavens publie les resultats satisfaisants obtenus par les injections intra-cerebro-ventriculaires (ICV) de morphine comme alternative a la voie intrathecale, rapidement suivi par differentes equipes, ce qui va permettre de developper la methode [5].

Morphine intra-cérébro-ventriculaire dans les douleurs cancéreuses

Douleur Neuropathique 4 Questionnaire

Objectif : savoir reconnaitre une douleur neuropathique et la prendre en charge. Les douleurs neuropathiques, liees a une lesion du systeme nerveux, representent une part importante des douleurs chroniques. Leur reconnaissance, qui s'appuie exclusivement sur la clinique, peut etre facilitee par l'utilisation d'outils comme le questionnaire DN4. Elles ne repondent pas ou peu aux antalgiques usuels et leur prise en charge repose, pour l'essentiel, sur les antiepileptiques et (ou) les antidepresseurs.

Douleurs neuropathiques : un diagnostic exclusivement clinique

Oligomannose‐type glycans on the spike protein of HIV‐1 constitute relevant epitopes to elicit broadly neutralizing antibodies (bnAbs). Herein we describe an improved synthesis of α‐ and β‐linked hepta‐ and nonamannosyl ligands that were subsequently converted into BSA and CRM197 neoglycoconjugates. We assembled the ligands from anomeric 3‐azidopropyl spacer glycosides from select 3‐O‐protected thiocresyl mannoside donors. Chain extensions were achieved using [4+3] or [4+5] block synthesis of thiocresyl and trichloroacetimidate glycosyl donors. Subsequent global deprotection generated the 3‐aminopropyl oligosaccharide ligands. ELISA binding data obtained with the β‐anomeric hepta‐ and nonamannosyl conjugates with a selection of HIV‐1 bnAbs showed comparable binding of both mannosyl ligands by Fab fragments yet lesser binding of the nonasaccharide conjugate by the corresponding IgG antibodies. These results support previous observations that a complete Man9 structure might not be the preferred antigenic binding motif for some oligomannose‐specific antibodies, and have implications for glycoside designs to elicit oligomannose‐targeted HIV‐1‐neutralizing antibodies.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbic.202200061

Jean Bruxelle

Papers

Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4)

Morphine intra-cérébro-ventriculaire dans les douleurs cancéreuses

Douleur Neuropathique 4 Questionnaire

Douleurs neuropathiques : un diagnostic exclusivement clinique

Synthetic Neoglycoconjugates of Hepta‐ and Nonamannoside Ligands for Eliciting Oligomannose‐Specific HIV‐1‐Neutralizing Antibodies