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There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics.A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results.Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment.This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials.This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment.

International audience; Introduction: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. Materials and Methods: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. Results: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). Discussion: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. Conclusion: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

Background Central post-stroke pain (CPSP) can arise after lesions anywhere in the central somatosensory pathways, essentially within the spinothalamic system (STS). Although the STS can be selectively injured in the mesencephalon, CPSP has not been described in pure midbrain infarcts. Methods Of more than 300 CPSP consecutive cases, we describe five patients who developed definite neuropathic pain following lesions circumscribed to the postero-lateral mesencephalon. Results The mesencephalic lesion responsible for pain was always haemorrhagic and always involved the spinothalamic tract (STT), as demonstrated by suppressed laser-evoked potentials in every case, with or without preserved lemniscal function. In three cases the midbrain injury could be ascribed to trauma, presumably from the cerebellar tentorium. As a result of the paucity of sensory symptoms, the pain was considered as 'psychogenic' in two of the patients until electrophysiological testing confirmed STT involvement. Conclusion Postero-lateral midbrain lesions should be added to potential causes of CPSP. Because pain and spinothalamic deficits may be the only clinical sign, and because small lateral midbrain lesions may be difficult to trail with MRI, mesencephalic CPSP can be misdiagnosed as malingering or psychogenic pain for years. Significance Selective spinothalamic injury caused by small lateral midbrain lesions is a very rare cause of central post-stroke pain that can remain undiagnosed for years. It appears to obey to haemorrhagic, sometimes post-traumatic lesions. Sudden development of contralateral burning pain with isolated spinothalamic deficits may be the only localizing sign, which can be easily objectively detected with electrophysiological testing.

Purpose Intravenous ketamine is often prescribed in severe neuropathic pain. Oral N-methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine. Patients and methods A multicenter randomized controlled clinical trial included 60 patients after ketamine infusion for refractory neuropathic pain. Dextromethorphan (90 mg/day), memantine (20 mg/day) or placebo was given for 12 weeks (n=20 each) after ketamine infusion. The primary endpoint was pain intensity at one month. Secondary endpoints included pain, sleep, anxiety, depression, cognitive function and quality of life evaluations up to 12 weeks. Results At 1 month, dextromethorphan maintained ketamine pain relief (Numeric Pain Scale: 4.01±1.87 to 4.05±2.61, p=0.53) and diminished pain paroxysms (p=0.03) while pain intensity increased significantly with memantine and placebo (p=0.04). At 3 months, pain remained lower than at inclusion (p=0.001) and was not significantly different in the three groups. Significant benefits were observed on cognitive-affective domains and quality of life for dextromethorphan and memantine (p Conclusions Oral dextromethorphan given after ketamine infusion extends pain relief during one month and could help patients to better cope with pain. Future studies should include larger populations stratified on pharmacogenetics screening. Optimization of an oral drug that could extend ketamine antihyperalgesia, with fewer hospital admissions, remains a prime challenge in refractory neuropathic pain.

International audience; BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P

Background T‐type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T‐type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. Methods This proof‐of‐concept, multicentre, double‐blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add‐on therapy) to an inactive control (IC) in 114 patients with non‐diabetic peripheral neuropathic pain. After a 7‐day run‐in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention‐to‐treat population. This study is registered with EudraCT (2013‐004801‐26) and ClinicalTrials.gov (NCT02100046). Results The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per‐protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI −25.8; −5.4) from baseline compared to IC (−7.8%, 95% CI −14.3; −1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. Conclusion Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. Significance This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per‐protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T‐type calcium channel inhibition for the treatment of neuropathic pain.

Aims: To identify structural changes in gray matter in suspected migraine generators (the hypothalamus and/or brainstem nuclei) and pain pathways and to evaluate whether structural changes in migraine are definitive or resolve with age. Methods: Voxel-based morphometry (VBM) was used to assess differences in gray matter between 39 healthy controls (HC), 25 episodic migraine (EM) subjects, and 37 subjects with a history of migraine (HM). In addition, morphometric changes were specifically investigated in suspected migraine generators and/ or pain pathways. For statistical analyses, t tests between the groups were performed, and a correction for multiple comparisons was used. Results: Wholebrain analysis did not reveal any gray or white matter changes. However, when the analysis was limited to the pain matrix, a lower gray matter volume was observed in the left second somatosensory (SII) cortex in EM subjects compared to HC subjects. This volume was significantly reduced in the EM group compared to the HC group and to the HM group, but not in the HM group compared to the HC group. Conclusion: Morphometric abnormalities in the SII in subjects with ongoing migraine but not in subjects with a resolved migrainous disease are likely to characterize a migrainous state rather than be a marker of brain susceptibility to migraine.

Resume Les NPF sont liees a des dysfonctions des fibres de petit calibre peu myelinisees Aδ et/ou amyeliniques C. Cliniquement on distingue des NPF longueur-dependantes et des NPF non longueur-dependantes. Les NPF sont dites mixtes si elles associent egalement une atteinte des fibres sensitives de gros calibre se traduisant par une alteration des vitesses de conduction en electroneuromyographie. Dans le cas contraire elles sont dites pures. Pour les objectiver, il faut recourir a des tests comme la biopsie cutanee ou les potentiels evoques laser. La recherche des etiologies est guidee par l’interrogatoire et l’examen clinique et par un bilan biologique de debrouillage. Le traitement sera si possible etiologique. Le traitement des douleurs neuropathiques est imperatif, mais il s’avere parfois decevant en particulier dans les formes pharmaco-resistantes. La decouverte de chanellopathies associees aux NPF devrait permettre de demembrer un certain nombre de NPF considerees jusqu’a present comme des NPF idiopathiques, et pourrait peut-etre permettre des avancees therapeutiques significatives.

Repetitive transcranial magnetic stimulation (rTMS) is a procedure increasingly used to treat patients with central neuropathic pain, but its efficacy is still under debate. Patients with medically refractory chronic central neuropathic pain were included in 2 randomized phases (active/sham), separated by a wash-out period of 8 weeks. Each phase consisted of 4 consecutive rTMS sessions and a final evaluation session, all separated from one another by 3 weeks. High-frequency (20 Hz) rTMS was delivered over the primary motor cortex (M1) contralateral to the patient's pain using a neuronavigated robotic system. Patients and clinicians assessing outcomes were blinded to treatment allocation during the trial. The primary outcome measured the percentage of pain relief (%R) from baseline. Secondary outcomes were VAS score, Neuropathic Pain Symptom Inventory, analgesic drug consumption, and quality of life (EQ-5D). Thirty-six patients performed the entire study with no adverse effects. The analgesic effect for the main criterion (%R) was significantly higher in the active (33.8% confidence interval [CI]: [23.88-43.74]) than in the sham phase (13.02% CI: [6.64-19.76]). This was also the case for the secondary outcome VAS (-19.34% CI: [14.31-25.27] vs -4.83% CI: [1.96-8.18]). No difference was observed for quality of life or analgesic drug consumption. Seventeen patients (47%) were identified as responders, but no significant interaction was found between clinical and technical factors considered here and the analgesic response. These results provide strong evidence that 3 weeks spaced high-frequency rTMS of M1 results in a sustained analgesic effect and support the clinical interest of this stimulation paradigm to treat refractory chronic pain.

Distortions of body representation have been reported in Complex Regional Pain Syndrome (CRPS). The perception of sensations arising without external triggers (spontaneous sensations or SPS) was assessed here as a means of investigating distortions of body representation and awareness in CRPS. To avoid confounds between CRPS symptoms and SPS, lower-limb CRPS patients were included, whereas SPS were tested on the hands. Patients and controls were required to focus on their hands and to report the spatial and qualitative characteristics of SPS arising there. We found an ipsilateral decrease in the perception of thermal, pain-related and surface/mechanical SPS, as well as in the number of SPS-sensitive areas. The latter finding was predicted by decreased body awareness as assessed through questionnaires. A bilateral decrease in the perception of paresis-like SPS was also observed. Finally, the ipsilateral spatial distribution of SPS frequency and intensity underwent a shift from the fingers towards the lower parts of the palm. CRPS is likely to distort patient’s body perception and awareness of the entire half-body ipsilateral to the affected limb, and even of both sides. Such disturbances are not manifested solely as a decrease in sensitivity, but sometimes as shifts in the spatial distribution of sensitivity.

Background Repetitive transcranial magnetic stimulation (rTMS) appears as a useful tool to alleviate neuropathic pain but only few data are available for the long-term benefit of this treatment. Methods Here we report the effects of rTMS sessions, considered as a possible therapy for pain relief after a failure of different medications in patients with central (neuropathic) pain. We review here the prospectively collected data of the first forty patients treated as follow: 20 Hz stimulation delivered over the contralateral primary motor cortex (M1), each 3–4 weeks. Results A total of 440 rTMS sessions was collected (mean sessions number: 11, range: 1–37, follow-up 312 days on average, maximum 2.8 years). After four sessions, nine patients (22.5%) discontinued rTMS because of a lack of efficiency (

Summary Study aim In this study, evoked potentials (EPs) to a pneumatic, innocuous, and calibrated stimulation of the skin were recorded in 22 volunteers. Methods Air-puff stimuli were delivered through a home-made device (INSA de Lyon, Laboratoire Ampere, CHU de Saint-Etienne, France) synchronized with an EEG recording (Micromed ® ). Results A reproducible EP was recorded in 18 out of 22 subjects (82% of cases) with a mean latency of about 120–130 ms, and maximal amplitude at Cz. This EP actually consisted of two components, an auditory and a somatosensory one. Indeed, it was significantly decreased in amplitude, but did not disappear, when the noise generated by the air-puff was masked. We also verified that a stimulation close to the skin but not perceived by the subject was not associated with any EP. Conduction velocity between hand and shoulder was calculated around 25 m/s. Conclusions This preliminary study demonstrates that pneumatic EPs can be recorded in normal volunteers.

Standard neurophysiological techniques evaluate exclusively large myelinated fibers, but are not useful to explore sensory small fibers. Quantitative sensory tests have been developed to explore the thermal nociceptive function but this exploration is only subjective. Laser evoked potentials (LEPs) represent a noninvasive and objective test to explore thermal and nociceptive pathways. The clinical interest of LEPs have been assessed recently in the diagnosis of small fibers sensory neuropathies. In routine, the determination of detection and nociceptive thresholds, the analysis of N2P2 latencies and amplitudes enable demonstration of a dysfunction of A delta nerve fibers, to quantify these lesions and to determine whether the neuropathies are length-dependent or not. The LEP amplitude is negatively correlated to deafferentation. The interest of LEPs remained to be studied compared to skin biopsy.

The intensity of experimental pain is known to be dependent on stimulation duration. However, it remains unknown whether this effect arises largely from the actual stimulus duration or is substantially influenced by the subject's perception of the stimulus duration. In the present study, we questioned this issue by misleading the perception of the duration of pain in a population of 36 healthy volunteers stimulated with a thermode. To this aim, time was signified by a clock with rotating hands in which imperceptible differences in speed rotation had been introduced. Subjects were therefore immersed in 2 comparative conditions in which time was manipulated to provide the illusion of either long or short duration of the painful stimulus. In a first condition ("full-length" clock), participants were instructed that pain would last for a complete revolution of the clock's hands, whereas in the second condition ("shortened" clock), revolution was reduced by 25%. Although the intensity and the real duration of stimulation were identical in both conditions, the intensity of pain was significantly reduced when the perception of time was misleadingly shortened by the manipulated clock. This study suggests that the perceived duration of a noxious stimulation may influence the perceived intensity of pain. The perceived duration of the length of a noxious stimulation influences (decreases) the intensity of perceived pain.

Objectives To confirm and extend previous results involving repetitive transcranial magnetic stimulation (rTMS) aimed at alleviating refractory central neuropathic pain (CNP). To evaluate pain relief in detail and to assess ongoing benefits after one year of treatment. Design Prospective observational study. Setting University hospital. Outpatient settings. Participants Patients (N=80) with chronic central pain after brain or spinal cord injuries. Interventions High-frequency (20Hz) neuronavigated-rTMS sessions were applied on the primary motor cortex using a figure-of-eight coil positioned by a robotized arm. Patients received a minimum of 4 consecutive sessions, each separated by 3-4 weeks. Main Outcome Measures Percentage of pain relief (%R), duration of pain relief (DPR), numeric rating scale (NRS), neuropathic pain symptom inventory (NPSI), and pain relief score (PRS). Results Seventy-one patients completed the study. On average, after the first 4 sessions, %R was 28% and DPR was 11 days. Fifty-four patients (76%) were responders with a permissive threshold of ≥10%R and 61% (43 patients) with a stringent threshold ≥30%R. After 12 months of treatment (15 sessions) we observed a cumulative effect on %R (48%), DPR (20d), and on the prevailing NPSI sub-score (-28%). This effect reached significance after 4 sessions and was further maintained over 12 months. Across participants, more than 1000 rTMS sessions were delivered over 6 years without any adverse effect. Conclusion These results confirm that multiple rTMS sessions are both safe and have potential as a treatment for CNP. An ongoing randomized controlled trial will allow teasing out of this effect from placebo analgesia.

Central pain with dissociated thermoalgesic sensory loss is common in spinal and brainstem syndromes but not in cortical lesions. Out of a series of 270 patients investigated because of somatosensory abnormalities, we identified five subjects presenting with central pain and pure thermoalgesic sensory loss contralateral to cortical stroke. All of the patients had involvement of the posterior insula and inner parietal operculum. Lemniscal sensory modalities (position sense, graphaestesia, stereognosis) and somatosensory evoked potentials to non-noxious inputs were always preserved, while thermal and pain sensations were profoundly altered, and laser-evoked potentials to thermo-nocoiceptive stimuli were always abnormal. Central pain resulting from posterior parasylvian lesions appears to be a distinct entity that can be identified unambiguously on the basis of clinical, radiological and electrophysiological data. It presents with predominant or isolated deficits for pain and temperature sensations, and is paradoxically closer to pain syndromes from brainstem lesions affecting selectively the spinothalamic pathways than to those caused by focal lesions of the posterior thalamus. The term 'pseudo-thalamic' is therefore inappropriate to describe it, and we propose parasylvian or operculo-insular pain as appropriate labels. Parasylvian pain may be extremely difficult to treat; the magnitude of pain-temperature sensory disturbances may be prognostic for its development, hence the importance of early sensory assessment with quantitative methods.

Background.—Whereas the clinical features of pure triptan overuse headache (TOH) are well known, there are insufficient data regarding the semiological pattern of headaches when triptan overuse is associated with other types of medication overuse. Objective.—To investigate and compare the clinical characteristics of patients with pure TOH and those with medication overuse headaches associating triptan and other medication overuses (combined TOH). Methods.—This cross-sectional, observational study was conducted in 7 tertiary-care headache centers participating in the French Observatory of Migraine and Headaches. From 2004 to 2006, data from 163 patients with TOH were collected in face-to-face structured interviews (according to the International Classification of Headache Disorders, 2nd edition criteria). Results.—Eighty-two patients fulfilled criteria for pure TOH (pTOH patients) and 81 for combined TOH (cTOH) patients. Continuous headaches were reported in 76% of cTOH patients compared with 32% of pTOH patients. Significantly more frequent and severe headaches and more intense phono-/photophobia between attacks were noted in cTOH patients. More cTOH than pTOH patients reported a history of tension-type headaches and a long-standing history of chronic headaches. Finally, compared with pTOH patients, cTOH patients were characterized by stronger dependence on acute treatments of headaches according to the DSM-IV criteria. Conclusions.—Combined therapy with analgesics and/or the total number of drug units taken per day may cause a shift from a pattern of clear-cut headache attacks in patients with pTOH toward more severe clinical presentation in patients with cTOH. These patients should receive more intensive prophylactic therapy and specific behavioral management.

Objective.— The aim of this study was to assess behavioral dependence on migraine abortive drugs in medication-overuse headache (MOH) patients and identify the predisposing factors. Background.— It is common occurrence that MOH patients relapse after medication withdrawal. Behavioral determinants of medication overuse should therefore be identified in MOH patients. Methods.— This was a cross-sectional, multicenter study that included 247 MOH patients (according to International Classification of Headache Disorders, 2nd edition criteria) consulting in French headache specialty centers. Face-to-face interviews were conducted by senior neurologists using a structured questionnaire including the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for the evaluation of dependence, Hospital Anxiety and Depression Scale for the evaluation of anxiety and depression, and 6-item short-form Headache Impact Test scale for the determination of functional impact. Results.— Most MOH patients had pre-existing primary migraine (87.4%) and current migraine-type headaches (83.0%). Treatments overused included triptans (45.8%), opioid analgesics alone or in combination (43.3% of patients), and analgesics (27.9%). Nonmigraine abortive substances (tobacco, caffeine, sedatives/anxiolytics) were overused by 13.8% of patients. Two-thirds of MOH patients (66.8%) were considered dependent on acute treatments of headaches according to the DSM-IV criteria. Most dependent MOH patients had migraine as pre-existing primary headache (85.7%) and current migraine-type headaches (87.9%), and most of them overused opioid analgesics. More dependent than nondependent MOH patients were dependent on psychoactive substances (17.6% vs 6.1%). Multivariate logistic analysis indicated that risk factors of dependence on acute treatments of headaches pertained both to the underlying disease (history of migraine, unilateral headaches) and to drug addiction (opioid overuse, previous withdrawal). Affective symptoms did not appear among the predictive factors of dependence. Conclusion.— In some cases, MOH thus appears to belong to the spectrum of addictive behaviors. In clinical practice, behavioral management of MOH should be undertaken besides pharmacological management.

Introduction : Les activations cerebrales survenant lors d’une stimulation douloureuse sont maintenant bien identifiees en imagerie fonctionnelle [1, 2]. Une des questions restant ouverte est la signification physiologique de chacune des activites observees, et la probable association d’activites de signification physiologique differentes effectuees en parallele au niveau cerebral. Pour l’experience douloureuse, une des questions concerne l’anticipation d’une stimulation connue, deja vecue et reconnue comme telle. Dans cette situation, les donnees d’une experience menee par Cruccu [3] demontrent que l’amplitude du potentiel evoque nociceptif cerebral est d’autant plus importante que l’attente a ete prolongee. Ces donnees suggerent que la phase d’anticipation peut influencer la “matrice d’activation” contemporaine de la phase de stimulation douloureuse effective. Notre etude vise a preciser cet aspect des choses. Elle inclut donc, avant la phase douloureuse proprement dite, une phase d’anticipation douloureuse signalee au sujet volontaire par une alerte sonore lui indiquant l’imminence d’une stimulation douloureuse delivree par laser. Cette periode anticipatoire a une duree aleatoire variant entre des extremes de 3 a 9 secondes. La stimulation laser est constituee d’un train de 5 impulsions permettant ainsi de verifier le recrutement d’une matrice d’activation nociceptive.

Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior-posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients' work up, and the results replicated by other investigators in the field.

Resume A l’heure actuelle, on estime que 12% de la population francaise souffre de migraine, soit 6 a 7 millions de personnes (4). La migraine transformee avec abus medicamenteux est une complication de la migraine se caracterisant par l’augmentation parallele de la frequence des cephalees et des consommations d’antalgiques qui deviennent quotidiennes. En France, la prevalence de cette pathologie est de 3% (10). La migraine transformee est une pathologie invalidante du fait de ses repercussions dans la vie des individus en termes de handicap (dans les activites quotidiennes, professionnelles ou sociales). De meme, la migraine transformee est associee a un mauvais ajustement emotionnel avec des troubles anxio-depressifs plus frequents que chez les patients atteints de migraine (19). La qualite de vie des migraineux transformes est donc tres alteree. L’objectif de notre etude est de mettre en evidence des differences en termes de consequences emotionnelles et fonctionnelles de ces pathologies, mais egalement de rechercher les strategies d’ajustement mises en place par 30 migraineux « simples » (MS) et 32 patients souffrant de migraine transformee avec abus medicamenteux (MT). Differentes analyses statistiques ont permis de mettre en evidence des differences significatives en termes de detresse emotionnelle, avec un score plus important chez les MT. En revanche, on ne retrouve aucune difference significative entre nos 2 populations concernant le handicap lie aux sensations douloureuses. De plus, les MT se caracterisent par l’utilisation de strategies de coping dysfonctionnelles telles que la dramatisation, la distraction et la priere. Au vu de ces resultats, il semble interessant d’etudier plus amplement ces strategies chez les MT, notamment sur un suivi longitudinal au sorti d’un sevrage medicamenteux.

Objectives.—To construct and validate a questionnaire measuring dependence on analgesics and on migraine attack treatments in headache patients. Method.—The items were obtained using the Diagnostic and Statistic Manual of Mental Disorders (4th ed.) (DSM-IV) diagnostic criteria for dependence. The construct validity of the scale was investigated by confirmatory analysis in a sample of 156 patients. Regression analysis was used to explore predictive validity. Results.—The 21 items of the scale were grouped into seven first-order factors corresponding to seven dependence items described in the DSM-IV. There was a second-order factor that may be considered as a general dependence factor. The global questionnaire score predicted the number of units of treatment taken per week, the number of days of headache, the number of days medications were taken, and emotional distress. Patients with headache associated with chronic substance use had a significantly higher score (P < .000) than migraine and tension headache patients. Conclusion.—It is a practical and valid tool for measuring medication dependence, including the behavioral dimension of dependence, in patients with headache associated with chronic substance use. It can prevent patients and clinicians from only focusing on pharmacological dependence.

Resume Propos. – La douleur faciale est un symptome frequent dont l'etiologie est parfois difficile a identifier. Bien que l'interrogatoire et l'examen clinique permettent facilement le diagnostic de certaines entites cliniques bien definies (nevralgie faciale, neuropathie faciale, algie vasculaire), un grand nombre d'affections de la face (sinusites, odontalgies, dysfonctionnement temporomandibulaire) peuvent emprunter certains symptomes de ces grands tableaux expliquant les difficultes diagnostiques. Actualites et points forts. – Les facteurs anatomiques et physiologiques de la nociception faciale expliquent la grande diversite des tableaux cliniques des algies faciales. Bien que leur symptomatologie soit assez bien codifiee leurs mecanismes demeurent encore imparfaitement connus. Plusieurs facteurs (psychogeniques, neuropathiques, endocriniens...) et differents mecanismes (neuropathique, vasculaire, myo-articulaire...) peuvent s'intriquer expliquant les difficultes diagnostiques et therapeutiques. Perspectives et projets. – Une meilleure connaissance des caracteristiques cliniques et implications therapeutiques des causes d'algies faciales typiques et atypiques permet d'ameliorer la prise en charge des patients, d'eviter le nomadisme medical, les procedures medicales inutiles et la non-compliance au traitement.

Il existe peu de donnees sur les facteurs de modulation des PELs chez les patients qu’il s’agit de l’influence de leur douleur chronique, de leur terrain ou des medicaments. Dans ce contexte, nous avons analyse les PELs de 75 patients adresses au CHU de Saint-Etienne pour suspicion de douleurs neuropathiques strictement unilaterales et 33 sujets sains. Les patients devaient avoir beneficie de stimulations par un laser YAP en C3 et/ou sur la main, et d’une exploration clinique standardisee. Il s’agissait de 47 patients avec lesion identifiee du systeme nerveux et 28 sans atteinte electrophysiologie ni en imagerie. 48 patients prenaient des traitements isoles ou combines (32 sous antiepileptiques, 13 sous antidepresseurs, 13 sous benzodiazepines, 7 sous antalgiques). Quel que soit le territoire explore, nous n’avons retrouve aucune difference de seuils perceptifs ou nociceptifs, d’amplitude de N2P2, de latence de N2 ou de P2 entre le cote sain des patients et les temoins. Chez les patients, l’âge etait correle aux latences de N2, de P2 et inversement correle aux amplitudes de N2P2 par stimulation C3 et des mains. L’augmentation d’amplitude de N2P2 notee en l’absence de lesion identifiee du systeme nerveux perdait sa significativite apres ajustement sur l’âge. Nous n’avons pas retrouve d’influence du BMI, du type de douleur sur les PELs. Nous n’avons pas mis en evidence de difference entre les patients avec ou sans traitements tant sur les seuils que sur les PELs. Cette etude rappelle l’importance d’interpreter les resultats des PEL en fonction de l’âge [1] . L’influence des traitements de fond et en particulier des anti-epileptiques semble negligeable contrairement a ce qui a ete observe anterieurement [2] . Toutefois, il sera necessaire de poursuivre ce travail sur un effectif plus large de patients pour etudier specifiquement l’effet de chaque classe pharmaceutique.

Nous rapportons ici notre premiere experience clinique d’utilisation de la stimulation magnetique transcrânienne repetitive (rTMS) dans les douleurs neuropathiques centrales rebelles aux traitements medicamenteux [1] . L’etude porte sur des donnees collectees prospectivement pendant 4 ans sur 40 patients. Les seances etaient organisees toutes les 3-4 semaines avec une neuronavigation et une assistance robotisee corrigeant les mouvements de tete. La stimulation portait sur le cortex moteur primaire (M1) controlateral a la douleur (20 Hz, Intensite a 80 % du seuil moteur, 20 trains consecutifs de 80 stimulations separes de 84 s). L’etude portait sur un total de 440 seances de rTMS (moyenne : 11, ecart de 1 a 37, suivi de 312 jours en moyenne, maximum 2,8 ans). Apres 4 seances, 9 patients (22,5 %) ont arrete la rTMS a cause d’un manque d’efficacite (

Il s’agit d’un probleme important de Sante Publique puisque 30% de la population francaise se plaint de cephalees repetitives. La prise en charge comporte trois etapes successives qui ont chacune leur importance.

Objectifs: etude de la comorbidite pour les troubles lies a l’utilisation de substances psychoactives chez les patients souffrant de cephalees par abus medicamenteux.Methode: etude comparative de quarante et un migraineux (MIG) et quarante et un patients souffrant de cephalees par abus medicamenteux issus de migraines (CAM).Resultats: les CAM ulilisant des medicaments contenant des substances psychoactives (cafeine et codeine) remplissent dans la majorite des cas les criteres du DSM-IV pour la dependance aux substances. Il existe un risque plus important de souffrir de troubles lies a l’utilisation de substances psychoactives autres que les antimigraineux de crise (OR=7,6 [2,2–26,0]) chez les CAM que chez les MIG. L’etude retrospective de la chronologie de survenue des troubles montre que la survenue d’un trouble lie a l’utilisation de substances autres que les antimigraineux de crise est predictive du risque de transformation de la migraine en CAM. Enfin, il y a une transmission familiale croisee entre CAM et troubles lies a l’utilisation de substances autres que les antimigraineux de crise.Conclusion: cette etude donne des arguments en faveur de l’appartenance de certains cas de CAM au spectre des addictions.

Introduction: Aging has been reported to reduce the amplitude of laser evoked potentials. However, it is unknown whether this effect depends on the length of the sensory fibers. This is an important issue, because most painful neuropathies are length-dependent. Methods: We conducted a study of 40 healthy subjects, half of whom were older than age 50 years. Nociceptive stimuli were delivered to the feet and thighs using a CO2 laser stimulator. Results: Detection and pain perception thresholds did not correlate with age. Latencies of N1, N2, and P2 correlated positively with age on the feet but not on the thighs, whereas the amplitude of N2-P2 decreased with age for both areas. Conclusions: The effects of aging on latencies may reflect a distal loss of peripheral inputs and a length-dependent de-synchronization of the ascending nociceptive volley. Additional changes in peripheral and central processes may explain the diffuse decrease of N2-P2 amplitudes observed with aging. Muscle Nerve 51:736–742, 2015

Introduction Une electrode concentrique induisant un stimulus douloureux permet l’enregistrement de potentiels evoques nociceptifs (PENec) caracterises par une reponse de vertex N2/P2. L’objectif de ce travail est de mettre en evidence les eventuelles modifications des PENec suite a l’activation des controles inhibiteurs diffus de la nociception (CIDN) par cold pressor test (CPT) chez le sujet sain. Materiel et methodes Les PENec sont enregistres chez 15 sujets sains (10 femmes, 5 hommes) qui ont signe un consentement. La stimulation utilise une electrode circulaire de type ELEC PAIN placee a l’index droit. L’intensite, constante lors des 4 temps, correspond au seuil nociceptif (moyenne : 7,7 mA). La frequence de stimulation est de 0,2 Hz. Le temps d’analyse est d’une seconde. La bande passante est de 0,3 a 100 Hz. Les reponses N2/P2 sont analysees en Cz avec une reference au nez. Le protocole comprend 4 temps (T1, T2, T3 et T4). Afin d’etudier une eventuelle habituation, T1 et T2 sont realises a 2 minutes d’intervalle avant l’activation du CIDN par CPT (pied gauche dans la glace pendant 5 minutes). T3 debute 2 minutes apres le CPT et T4 30 minutes apres T3. Chaque temps comporte deux series de 20 stimulations. Resultats Les PENec sont superposables aux temps T1 et T2. Le CPT induit une diminution significative de la perception douloureuse (EVA) et de l’amplitude du potentiel N2/P2. Elle est de 16,5 μV en T3, 22,6 μV en T1 et 21,1 μV en T2 (p Conclusions La repetition des stimulations n’induit pas d’habituation. La diminution de la douleur subjective (EVA) et de l’amplitude des PENec apres le CPT serait secondaire a la mise en route du CIDN. La persistance de cette diminution apres 30 minutes pourrait correspondre a un post-effet durable.

Introduction Une stimulation par air pulse permet l’enregistrement de potentiels evoques pneumatiques (PEP) sous la forme d’une reponse de vertex de longue latence N2/P2 (Conde et al., 2013). A temperature ambiante, la stimulation pneumatique est vehiculee par les fibres Abeta ; refroidie, elle l’est aussi par les fibres Adelta ou non myelinisees. Les PEP a l’air ambiant ou froid sont identiques (donnees personnelles). L’objectif de ce travail est d’etudier une eventuelle modification des PEP chez sujet sain, lors de l’activation des controles inhibiteurs diffus de la nociception (CIDN). Materiel et methodes Les PEP ont ete enregistres chez 16 sujets sains (9 hommes, 7 femmes) selon le protocole suivant : air ambiant puis air froid avant et immediatement apres activation du CIDN par 5 minutes de Cold Pressor Test (CPT), puis une demi-heure plus tard. Un protocole complementaire a ete realise chez 12 des sujets (6 hommes, 6 femmes) : deux enregistrements des PEP a l’air pulse ambiant et froid (ordre randomise) a 5 minutes d’intervalle sans CPT. Les reponses N2/P2 etaient mesurees en Cz. Le stimulateur pneumatique de diametre 0,5 mm, delivrait un souffle de 350 kPa pendant 10 ms a un cm perpendiculairement a la peau. Le bruit (55dBHL) induit par la stimulation etait masque par un bruit blanc. La stimulation etait appliquee a la face dorsale de la main droite et le CPT au pied gauche. Chaque test comportait deux series de 20 stimulations. Les parametres d’enregistrement etaient : frequence de 0,2 Hz, bande passante de 0,3 a 100 Hz et temps d’analyse d’1s, reference nez. Resultats Les latences des PEP ne varient pas. Une diminution significative d’amplitude des PEP est observee apres le CPT : de 13,5 μV (SD 5,85) a 9,87 μV (SD 3,66) pour l’air ambiant ( p = 0,005) et de 11,8 μV (SD 5,53) a 9,16 μV (SD 4,82) pour l’air froid ( p = 0,004) et demeure apres une demi-heure. Elle existe aussi lors des deuxiemes mesures sans application de CPT : de 11,14 μV (SD 5,19) a 9,5 μV (SD 4,91) pour l’air ambiant ( p = 0,02) et de 12,19 μV (SD 5,94) a 9,71 μV (SD 3,92) pour l’air froid ( p = 0,02). Une diminution d’amplitude existe toujours entre la premiere et la deuxieme stimulation, independamment de la temperature, respectivement p = 0,005 et 0,04 pour le 1 e et le 2 e protocole. Discussion et conclusions La diminution d’amplitude des PEP apres le CPT peut traduire un effet du CIDN et la persistance de cette diminution d’amplitude lors du test tardif, un post-effet. La diminution d’amplitude des PEP lors du protocole sans CPT traduit un effet « premier test », voire un phenomene d’habituation. Ce phenomene d’habituation peut s’associer a voir mimer un effet du CIDN. La stimulation pneumatique tiede ou froide n’est jamais douloureuse et il n’est pas assure que le CIDN soit active chez le sujet sain. Ce protocole sera utilise chez les patients allodyniques.

Le diagnostic des neuropathies a petites fibres (NPF) pures requiere des tests neurophysiologiques specifiques. L’exploration quantitative de la sensibilite permet de confirmer et/ou depister de facon simple des anomalies de la sensibilite thermo-algique, mais reste un test subjectif. Parmi les differents PE nociceptifs, les PELs constituent une technique electrophysiologique fiable, non invasive, recommandee en premiere intention dans la mise en evidence d’une atteinte des fibres A delta [2] . Leur interpretation peut s’averer toutefois difficile en cas de pathologie centrale associee, chez des patients agites, non compliants. Les PEL sont frequemment normaux en cas d’allodynie isolee ou en cas d’atteinte selective des fibres C [1] . Selon une etude recente de Lefaucheur et al. [3] , les PEL semblent le test le plus sensible dans le diagnostic des NPF (79 %), suivis par conductance electrochimique cutanee (61 %), le seuil de detection au chaud (55 %), les reponses cutanees sympathiques (41 %) et le seuil de detection au froid (29 %), et ce en considerant une population ayant au moins un test anormal sur les cinq realises. Leur combinaison pourrait ameliorer la precision du diagnostic de NPF. Parmi les autres tests explorant le systeme nerveux autonome on citera les explorations cardio-vagales, adrenergiques et les explorations des fibres sudoromotrices post-ganglionnaires par le test quantitatif du reflexe d’axone.

Objective To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on brain nociceptive responses (laser-evoked potentials, LEPs) and pain perception. Methods Twenty healthy subjects were included. Nociceptive CO2-laser pulses were sequentially delivered to the dorsum of both feet. The amplitude of LEPs and nociceptive thresholds were collected in three consecutive conditions: T1: “sham” TENS (2 Hz/low-intensity) positioned heterotopically, over the left thigh; T2: “active” TENS (120 Hz/low-intensity) applied homotopically, over the left common peroneal nerve; and T3: “sham” TENS (replication of condition T1). Results Compared with “sham” TENS, “active” TENS significantly decreased the LEPs amplitude. This effect was observed exclusively when “active” TENS was applied ipsilaterally to the painful stimulus. Nociceptive thresholds increased with sessions in both limbs, but the increase observed during the “active” condition of TENS (T2) exceeded significantly that observed during the condition T3 only on the foot ipsilateral to TENS. Conclusions Compared with a credible placebo TENS, high-frequency TENS induced a significant attenuation of both the acute pain and LEPs induced by noxious stimuli applied on the same dermatome. Significance This modulation of subjective and objective concomitants of pain processing reflects a real neurophysiological TENS-related effect on nociceptive transmission.

Background: Medication-overuse headache (MOH) management usually includes a medication withdrawal. The choice of withdrawal modalities remains a matter of debate. Methods: We compared the efficacy of in-patient versus out-patient withdrawal programmes in 82 consecutive patients with MOH in an open-label prospective randomized trial. The main outcome measure was the reduction in number of headache days after 2 months and after 2 years. The responders were defined as patients who had reverted to episodic headaches and to an intake of acute treatments for headache less than 10 days per month. Results: Seventy-one patients had a complete drug withdrawal (n = 36 in the out-patient group; n = 35 in the in-patient group). The reduction of headache frequency and subjective improvement did not differ between groups. The long-term responder rate was similar in the out- and in- patient groups (44% and 44%; p = 0.810). The only predictive factor of a bad outcome 2 years after withdrawal was an initial consumption of more than 150 units of acute treatments for headache per month (OR = 3.1; 95% confidence interval 1.1–9.3; p = 0.044). Conclusion: Given that we did not observe any difference in efficacy between the in- and out-patient withdrawals, we would recommend out-patient withdrawal in the first instance for patients with uncomplicated MOH.

Symptomatic cluster-like headaches have been described with lesions of the trigeminal and parasympathetic systems. Here, we report the case of a 44-year-old woman with continuous auricular pain and a positional cluster-like headache associated with red ear syndrome. Clinical data and morphological investigations raised the hypothesis of a neurovascular compression between the C3 root and vertebral artery. Neurosurgical exploration found a fibrosis surrounding both the C3 root and the vertebral artery. The excellent outcome after microvascular cervical decompression suggests a causal relationship between the cluster-like headache and the vertebral constraint on the C3 root.

We report here the case of a female patient who developed the following behavioural changes after a brain lesion involving the left posterior insula and SII cortices. She discovered de novo artistic capabilities for painting, with an episodic and compulsive need to paint ("hyperpainting"), but also exhibited changes in her ability to feel emotions. In addition, she had a typical neuropathic pain syndrome, including provoked pain and spontaneous pain, whose intensity was worsened when she painted with cold colours. This case-report suggests some kind of synaesthesiae, which has previously been reported for other sensory modalities. These findings suggest that a cross-talk between emotional, thermosensory, pain, and motivational functions may take place during recovery, at the level of the left insular-SII cortices.

We set out to study the role of psychiatric comorbidity in the evolution of migraine to medication overuse headache (MOH) by a comparative study of 41 migraineurs (MIG) and 41 patients suffering from MOH deriving from migraine. There was an excess risk of suffering from mood disorders [odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.5, 13.5], anxiety (OR = 5, 95% CI 1.2, 10.7) and disorders associated with the use of psychoactive substances other than analgesics (OR = 7.6, 95% CI 2.2, 26.0) in MOH compared with MIG. Retrospective study of the order of occurrence of disorders showed that in the MOH group, psychiatric disorders occurred significantly more often before the transformation from migraine into MOH than after. There was no crossed-family transmission between MOH and psychiatric disorders, except for substance-related disorders. MOH patients have a greater risk of suffering from anxiety and depression, and these disorders may be a risk factor for the evolution of migraine into MOH. Moreover, MOH patients have a greater risk of suffering from substance-related disorders than MIG sufferers. This could be due to the fact that MOH is part of the spectrum of addictive disorders.

Introduction La biopsie cutanee (BC) et les potentiels evoques laser (PEL) sont les deux examens de reference pour le diagnostic de neuropathie des petites fibres (NPF). Pourtant, ils n’ont jamais ete compares. Objectif Comparer les resultats de la BC et des PEL chez des patients presentant une neuropathie sensitive cliniquement pure avec une atteinte des petites fibres pure ou non. Materiel et methodes Nous avons realise une etude prospective monocentrique chez 50 patients. Douze avaient une NPF pure longueur-dependante (LD), 15 une neuronopathie (NNS) petites fibres pure, 12 une neuropathie sensitive distale mixte et 11 une NNS mixte. Les patients ont tous beneficie d’une BC proximale et distale sur un membre inferieur avec determination de la densite en fibres nerveuses intra-epidermiques, et d’un enregistrement du potentiel N2P2 en PEL (YAP ou CO2) sur 8 territoires. Resultats La BC et les PEL ont detecte une atteinte des petites fibres avec une sensibilite de 82 et 84 % respectivement. Cette difference n’est pas statistiquement significative. La concordance entre les deux techniques etait de 74%. Elle etait de 67 % et 82,6 % pour les NPF pures et les neuropathies mixtes respectivement. Les deux techniques ne sont pas performantes pour determiner le caractere LD ou non de la neuropathie avec une sensibilite respective de 46,7 % et 51 %. Discussion Notre etude confirme la bonne sensibilite de la BC et des PEL pour faire le diagnostic de NPF sans superiorite globale d’une technique. Elle montre une concordance correcte des deux explorations et leur faible performance pour determiner le caractere LD ou non de la neuropathie principalement en lien avec la frequence des atteintes proximales infracliniques. Conclusion La BC et les PEL sont deux techniques sensibles et concordantes pour l’etude des petites fibres nerveuses dans le cadre des neuropathies sensitives pures.