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      Pharmacological management of chronic neuropathic pain: Revised consensus statement from the Canadian Pain Society

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          Neuropathic pain is defined as a lesion or disease of the somatosensory system, and may involve the central or peripheral nervous systems. Treatment of neuropathic pain is a challenge for clinicians involved in affected patients' care. In 2007, the first guidelines for the treatment of neuropathic pain in the Canadian context were produced by the Canadian Pain Society. This update to these guidelines incorporates new evidence published since the first guidelines were released.



          Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians.


          To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management.


          RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013. Medications were recommended in the consensus statement if their analgesic efficacy was supported by at least one methodologically sound RCT (class I or class II) showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment were based on the degree of evidence of analgesic efficacy, safety and ease of use.


          Analgesic agents recommended for first-line treatments are gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors. Tramadol and controlled-release opioid analgesics are recommended as second-line treatments for moderate to severe pain. Cannabinoids are now recommended as third-line treatments. Recommended fourth-line treatments include methadone, anticonvulsants with lesser evidence of efficacy (eg, lamotrigine, lacos-amide), tapentadol and botulinum toxin. There is support for some analgesic combinations in selected NeP conditions.


          These guidelines provide an updated, stepwise approach to the pharmacological management of NeP. Treatment should be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Additional studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes and treatment of pediatric, geriatric and central NeP.

          Translated abstract

          HISTORIQUE :

          La douleur neuropathique (DNe), redéfinie comme une douleur causée par une lésion ou une maladie du système somatosensoriel, est un trouble invalidant dont sont affligés environ deux millions de Canadiens.

          OBJECTIF :

          Examiner les essais aléatoires et contrôlés (EAC) et les analyses systématiques liées à la prise en charge pharmacologique de la DNe pour préparer une déclaration de consensus révisée, fondée sur des faits probants, à l’égard de sa prise en charge.

          MÉTHODOLOGIE :

          Les EAC, les analyses systématiques et les lignes directrices sur la prise en charge pharmacologique de la DNe ont été évaluées lors d’une réunion de consensus en mai 2012, puis mises à jour en septembre 2013. Les médicaments étaient recommandés dans le document de consensus si leur efficacité analgésique était soutenue par au moins une EAC solide sur le plan méthodologique (classe I ou II), qui démontrait des avantages marqués par rapport à un placebo ou à un autre groupe témoin pertinent. Les recommandations thérapeutiques reposaient sur la qualité des preuves d’efficacité analgésique, d’innocuité et de facilité d’utilisation.

          RÉSULTATS :

          Les analgésiques recommandés pour le traitement de première intention sont les gabapentinoïdes (gabapentine et prégabaline), les antidépresseurs tricycliques et les inhibiteurs spécifiques du recaptage de la sérotonine et de la noradrénaline. Le tramadol et les opioïdes à libération contrôlée sont recommandés en deuxième intention pour la douleur modérée à grave. Les cannabinoïdes sont désormais recommandés en troisième intention, tandis que la méthadone, les anticonvulsivants dont l’efficacité est moins attestée (p. ex., lamotrigine, lacosamide), le tapentadol et la toxine botulique sont recommandés en quatrième intention. Certaines polythérapies analgésiques sont acceptées pour traiter des troubles de DNe particuliers.

          CONCLUSIONS :

          Ces lignes directrices fournissent une démarche mise à jour et graduelle pour la prise en charge pharmacologique de la DNe. Le traitement devrait être personnalisé en fonction de chaque patient, compte tenu de l’efficacité, du profil d’effets secondaires et de l’accessibilité du médicament, y compris son coût. D’autres études s’imposent pour faire des comparaisons directes entre analgésiques et examiner des combinaisons d’analgésiques, les résultats à long terme et le traitement de la DNe en pédiatrie, de la DNe en gériatrie et de la DNe centrale.

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          Most cited references 84

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          Neuropathic pain: redefinition and a grading system for clinical and research purposes.

          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.
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            Chi-Square Tests for Goodness of Fit and Contingency Tables

             Jacob Cohen (1977)
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              Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4).

              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.

                Author and article information

                Pain Res Manag
                Pain Res Manag
                Pain Research & Management : The Journal of the Canadian Pain Society
                Pulsus Group Inc
                Nov-Dec 2014
                : 19
                : 6
                : 328-335
                © 2014, Pulsus Group Inc. All rights reserved

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