How Should we Use Multicolumn Spinal Cord Stimulation to Optimize Back Pain Spatial Neural Targeting? A Prospective, Multicenter, Randomized, Double-Blind, Controlled Trial (ESTIMET Study).

BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001). CONCLUSION: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.

Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide: a randomized controlled trial in patients with peripheral neuropathic pain.

ABSTRACT: Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to 1 study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (Neuropathic Pain Symptom Inventory), Patient Global Impression of Change, anxiety, depression, and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and 7 days after the last administration were not significantly different between the 2 groups. However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain.

Assessment of procedural pain in French emergency departments: a multi-site, non-interventional, transverse study in patients with minor trauma injury.

Objective: To determine the mean number of procedural painful episodes per patient, and to retrieve information regarding diagnosis, therapeutic procedures and analgesic management, in patients visiting Emergency Departments (EDs) for minor trauma. Methods: This observational, non-interventional, multicenter study in adult patients was performed in 35 French EDs. All patients entering the EDs for minor trauma on a specified day between noon and 10 pm were registered; consenting patients were included in the study. Pain intensity was assessed using a verbal Numerical Rating Scale from 0 (no pain) to 10 (worst possible pain). An episode was described as painful if the difference in pain intensity between pain just before the procedure and maximal pain during the procedure was ≥2. Two independent nurses recorded data on 1 day in each center. Results: Overall, 909 patients were registered, 422 were included in the study, and complete data for 409 patients (1899 procedures) were available for analysis. The mean number of painful episodes per patient was 1.0 ± 1.3. Fifty-one percent of patients reported at least one painful procedure episode. Twenty-one percent of procedures were considered painful. Clinical examination was the procedure most often reported as painful. No preventive or curative analgesic treatment was reported in 95.1% of procedures. Conclusions: There is a need for improvement in routine pain assessment and, therefore, procedural pain management for ED patients. Specific protocols should be developed for procedural pain management, and teams should be trained especially for procedures usually not considered painful.

[Drug management of cancer-related peripheral neuropathic pain: A systematic review of the literature]. / Prise en charge médicamenteuse des douleurs neuropathiques périphériques liées au cancer : une revue systématique de la littérature.

The objective of the present systematic literature review was to provide an update on medical treatment of neuropathic pain in cancer patients. The number of cancer patients is steadily increasing. Pain is frequent in cancer patients. Few studies have focused on medical treatment of pain, and especially of neuropathic pain, in current or former cancer patients. The present systematic review of all studies published between December 2012 and August 2018 was intended to estimate the scale of this lack. In all, 27 articles were identified on a systematic PubMed search and from the authors' personal knowledge, confirming that scant data have been published. The heterogeneity of cancer patients, of cancer, and of pain go some way toward explaining this scarcity. Guidelines, founded mainly on results from non-cancer patients, recommend tricyclic antidepressants and antiepileptic drugs; local treatments have the advantage of good systemic tolerance. Larger-scale studies taking account of the etiology of neuropathic pain, its characteristics (strictly neuropathic or mixed) and patient characteristics (awaiting treatment, under treatment, recent or non-recent survivor, or in terminal phase) along the care pathway are needed to improve knowledge. The results of the present literature analysis can help future research.

Burden of cancer pain in developing countries: a narrative literature review.

Cancer pain is one of the most common, feared, debilitating, and often undertreated symptoms among cancer patients. It needs attention since it has a significant impact on the quality of life (QoL) of the patients. Also, since cancer has emerged as a major health problem in developing countries, there is a need to strengthen preventive strategies for effective cancer pain management and provide comfort to cancer patients. Nonetheless, various barriers limit developing countries toward optimal cancer pain management. To bridge the gap between adequate pain management and burden of cancer pain in developing countries, a comprehensive understanding of the limitations faced and the prevalence of cancer pain should be addressed. The aim of this literature review is to provide a deeper understanding on the factors associated with cancer pain as well as barriers toward optimal cancer pain management in developing countries. Some of the barriers addressed were administrative, judicial, economic, and professional barriers. Also, estimates on the prevalence of cancer pain and detrimental effects of pain on the QoL of cancer patients have been addressed. In summary, pain, which is one of the most debilitating symptoms of cancer, remains uncontrolled and undertreated in developing countries. It has a profound impact on the patient's QoL and can have physical, psychological, and social consequences; therefore, it needs to be managed urgently and appropriately. Most importantly, optimal treatment of cancer pain should be highlighted as a priority in developing countries and concerted efforts should be made to eliminate different barriers discussed in this review for effective and humane care.

Pain associated with health and economic burden in France: results from recent National Health and Wellness Survey data.

PURPOSE: This study aimed to estimate the prevalence of pain among French adults and assess the impact of pain on health-related quality of life (HRQoL), activity impairment, and health care resource use (HRU). PATIENTS AND METHODS: Respondents from the 2015 France National Health and Wellness Survey (N=19,173) were categorized by self-reported pain (experienced pain in the past 12 months vs no pain) and compared on HRQoL (36-Item Short Form Health Survey version 2: Mental Component Summary, Physical Component Summary, and Short Form-6 Dimensions health utilities), activity impairment (Work Productivity and Activity Impairment questionnaire), employment status, and HRU (health care provider visits, emergency room visits, and hospitalizations). Bivariate analyses examined differences between pain groups stratified by age, sex, income, and Charlson comorbidity index (CCI) scores. RESULTS: Pain prevalence was 20.2% (n=4007). Mean Physical Component Summary decrements with pain ranged from 3.4 to 8.1 points among those aged <35 years to those aged 45-54 years, respectively. Results for Mental Component Summary and Short Form-6 Dimensions scores followed similar patterns. Regardless of income, sex, or CCI group, pain was associated with significant decrements on all HRQoL measures (for all, p<0.05). The impact of pain on activity impairment was lowest among those <35 years; this impact was higher in middle age and then tapered off among those aged ≥75 years. Pain was associated with greater activity impairment and more health care provider visits across income, sex, and CCI groups (for all, p<0.05). Generally, emergency room visits were more common among those with pain across age, sex, and CCI, but they were only significantly associated with pain in the lower income group (p<0.01). Pain was associated with significantly more hospitalizations across age and income groups. CONCLUSION: Results suggest pain negatively affects HRQoL, activity impairment, and HRU across demographic subgroups. These findings help underscore the considerable health and economic burden of pain in France.

Tapentadol prolonged-release for moderate-to-severe chronic osteoarthritis knee pain: a double-blind, randomized, placebo- and oxycodone controlled release-controlled study.

OBJECTIVE: To assess efficacy and safety of tapentadol prolonged release (PR) for moderate-to-severe chronic osteoarthritis knee pain. METHODS: Patients (n = 990) were randomized (1:1:1) to tapentadol PR, oxycodone controlled release (CR; reference compound for assay sensitivity), or placebo for a double-blind 3-week titration and 12-week maintenance period. Primary efficacy end-points were change from baseline in average pain intensity at week 12 of maintenance (US end-point) and over the entire maintenance period (non-US end-point) with "last observation carried forward" as imputation method for missing scores. RESULTS: Both primary end-points were not significantly different for tapentadol PR nor for oxycodone CR vs placebo at week 12 (least squares [LS] mean difference = -0.3 [95% CI = -0.61-0.09]; p = 0.152 and 0.2 [95% CI = -0.16-0.54]; p = 0.279, respectively) and over the maintenance period (LS mean difference = -0.2 [95% CI = -0.55-0.07]; p = 0.135 and 0.1 [95% CI = -0.18-0.44]; p = 0.421, respectively). Considerably more patients receiving tapentadol PR than oxycodone CR completed the trial (58.3% vs 36.6%). This is consistent with better results with tapentadol PR on the overall health status (PGIC) compared to oxycodone CR. Indeed, respectively, 56% and 42.5% rated at least "much improved" at the end of treatment. Incidences of gastrointestinal adverse events were higher for both active treatments compared to placebo. Tapentadol PR was associated with a better gastrointestinal tolerability profile with incidences of constipation (17.9% vs 35%) and of the composite of nausea and/or vomiting (23.8% vs 46.8%) significantly lower vs oxycodone CR (p < 0.001). CONCLUSIONS: The study did not demonstrate assay sensitivity. The finding that both primary end-points for tapentadol PR were not met can, thus, not be interpreted. Tapentadol PR was better tolerated than oxycodone CR, largely due to fewer gastrointestinal side-effects.

[Formalized consensus: clinical practice recommendations for the management of the migraine in African adult patients]. / Consensus formalisé: recommandations de pratiques cliniques pour la prise en charge de la migraine du patient adulte africain.

Migraine is a primary headache disorder (according to the latest International Headache Society criteria) affecting approximately 8% of African population. Women are more often affected than men and attacks usually occur before the age of 40 years Although some treatments, hygienic-dietary measures and other non-pharmacological methods can reduce the intensity and frequency of attacks, medicinal treatment of migraine attack is often necessary. Availability of treatments and access to care differ in Africa and led to the implementation of the first expert consensus recommendations for the management of the migraine in african adult patients. This multinational collaborative study is intended for health practitioners. It aims to provide 16 simple, evidence-based recommendations and is adapted to african medical practice.

[Chronic pain management: societal impact]. / La prise en charge de la douleur chronique: un problème de société.

Pain is a real issue of public health, quality and evolution of a system of health test: this is a major social problem. Pain management meets a humanistic, ethical purpose and dignity of man because of the physical and psychological implications. It induces a disability which excludes the patient of society gradually or suddenly. The physical pain and mental suffering to all ages of life make more vulnerable people weakened by disease. Rebel chronic pain are sources of disability, disabilities, disability and major alterations in the quality of life. All of these data shows the impact of pain and its intensity on the professional conditions, on professional activity and productivity, on the use of care systems (very significant increase in medical consultations, hospitalizations), as well as on the mental and physical health. These results confirmed analyses which consider that the unrelieved pain has a major economic impact on care systems and constitutes a public health problem with around two thirds of persons professionally impacted by pain. The progress of medicine has helped the healing of certain serious diseases, but also favoured acute diseases to turn to chronic diseases. The result is an increase in of lifetime sometimes without disease, but this survival may be also accompanied by disease or disability. Progress, pain and suffering, the end of life, ethics will be the core of the basic thoughts of tomorrow.

Acute pain evaluation with Algoplus scale in Cambodian patients.

OBJECTIVE: Evaluation of acute pain in patients with language barriers is often difficult during humanitarian missions. Algoplus, a behavioral scale validated for acute pain evaluation in Caucasians with verbal communication difficulties, was tested during a clinical mission in Cambodia in patients admitted to hospital for acute pain. METHODS: Patients (N = 33, 19 men and 14 women [38 ± 3 years old]) suffering from acute pain were admitted to Calmette Hospital, Phnom Penh, Cambodia during June 2010. Patients spoke Khmer only; a medical trainee who did no speak Khmer performed the Algoplus scale, and a bilingual Khmer pain specialist doctor asked the patient to score pain intensity on a numerical scale (0-10). The relevance of the scale and of each item (facial expression, complaints, look, body position, and atypical behavior yes/no) was studied. Internal consistency was assessed by Cronbach alpha analysis and convergent validity by correlation coefficient. The relationship between Algoplus items and pain intensity was analysed. RESULTS: Pain intensity (6.3 ± 2.2) and Algoplus scores (2.1 ± 1.2) are correlated (r = 0.61, P < 0.001): increases in Algoplus are correlated to increases in pain intensity. Internal consistency is 0.51, and scales comparison per item is significant for facial expression (P = 0.028) and complaints (P = 0.005), but not for the other items. CONCLUSION: This feasibility study shows that despite a correlation with pain intensity, Algoplus may underestimate acute pain in this population. It is, however, an interesting tool for future studies to explore facial expression and complaints as proxies of pain in non-communicative patients.

[Evaluation of chronic pain]. / Evaluation du patient ayant une douleur chronique.

In 2007, the Plan for the improvement of the quality of life of people with chronic diseases stressed that support for pain was the first expectations of patient associations. And pain support is primarily the field of competence of the treating physician. It is in this context, that (HAS) recommendations were developed to promote the implementation of care tailored for people expressing a chronic pain. They advocate the support procedure: the identification and evaluation of the chronic pain in ambulatory (history, etiologic assessment, tests), the establishment of treatment or application with a specialized structure, diagnostic or therapeutic advice.

Barriers and approaches to the successful integration of palliative care and oncology practice.

As management of patients with cancer is evolving, an increased focus is being placed on individualized patient-centered care. Early integration of palliative care into the overall management of patients with cancer can help achieve this paradigm shift. Despite recommendations for earlier integration of palliative care by national and international societies, several barriers remain to achieving this goal. Survey studies have indicated a significant need for increased education regarding palliative care for both medical undergraduates and postgraduate physicians. Key issues in the early integration of palliative care include relationship-building across multiple health systems and specialties; development of a standardized definition of palliative care, making clear that it should be fully integrated with cancer-directed therapy; identification of physician and nonphysician champions; standardization of tools for patient assessment; education programs designed to meet the needs of health care professionals; and ongoing evaluation to assess program benefits and limitations.

Functional brain imaging of trigeminal neuralgia.

We used functional magnetic resonance imaging (fMRI) to analyze changes in brain activity associated with stimulation of the cutaneous trigger zone in patients with classic trigeminal neuralgia (CTN). Fifteen consecutive patients with CTN in the second or third division of the nerve, were included in this study. The fMRI paradigm consisted of light tactile stimuli of the trigger zone and the homologous contralateral area. Stimulation of the affected side induced pain in seven patients, but was not painful in eight patients on the day of the experiment. Painful stimuli were associated with significantly increased activity in the spinal trigeminal nucleus (SpV), thalamus, primary and secondary somatosensory cortices (S1, S2), anterior cingulate cortex (ACC), insula, premotor/motor cortex, prefrontal areas, putamen, hippocampus and brainstem. Nonpainful stimulation of the trigger zone activated all but three of these structures (SpV, brainstem and ACC). After a successful surgical treatment, activation induced by stimulation of the operated side was confined to S1 and S2. Our data demonstrate the pathological hyperexcitability of the trigeminal nociceptive system, including the second order trigeminal sensory neurons during evoked attacks of CTN. Such sensitization may depend on pain modulatory systems involving both the brainstem (i.e. periaqueductal gray and adjacent structures) and interconnected cortical structures (i.e. ACC). The fact that large portions of the classical 'pain neuromatrix' were also activated during nonpainful stimulation of the trigger zone, could reflect a state of maintained sensitization of the trigeminal nociceptive systems in CTN.

Effects of training on general practitioners' management of pain in osteoarthritis: a randomized multicenter study.

OBJECTIVE: To evaluate the effects of a short interactive training program for general practitioners (GP) on pain management in patients with osteoarthritis (OA). METHODS: A multicenter, parallel-group study. GP were randomized to receive training on relationships and communication, pain evaluation, prescription, and negotiation of a patient contract or to a control group receiving a presentation about obtaining consent in trials. Outcomes were patient assessments of pain and functional ability. We invited 1500 GP to take part in the study. Those who volunteered to receive the training recruited outpatients from May 2001 to April 2002. Patients participating in the evaluation of the effects of the general practitioners' training had lower limb OA and pain on motion [> or = 40 mm on a visual analog scale (VAS)] and had indications for treatment with acetaminophen. The primary endpoint: sum of patient pain relief based on the daily VAS self-evaluation during the 2 weeks of the trial. RESULTS: In total, 180 GP (84 trained, 96 nontrained) enrolled 842 patients (414 and 428, respectively). Mean baseline VAS pain was 63 +/- 14 mm. Patients in the trained-GP group had better overall pain relief (316 +/- 290 mm/day vs 265 +/- 243 mm; p < 0.0001), greater improvement in Lequesne and WOMAC scores (p < 0.0001), and better overall perception of treatment (p = 0.002). Acetaminophen use was slightly higher in the trained group; however, the difference in pain relief remained statistically significant (p = 0.0003) after adjustment for this difference. CONCLUSION: This is the first study to demonstrate a positive effect of physician training on patients with a painful condition.

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.