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Background: The neuropathic characteristics of pain occurring after an osteoporosis (OP)-related fracture are often under-recognized. The aim of this pilot study is to identify, in patients suffering from pain localized on the site of a previous osteoporotic fracture, the presence of neuropathic characteristics, their medical management, and their impact on quality of life. Methods: This pilot cross-sectional study on consecutive patients in University Hospital, Rheumatology Department, Clermont-Ferrand, France, was approved by the Ethics Committee (IRB number 2023-CF34). Pain was evaluated with the Numeric Pain Rating Scale (NPRS), Neuropathic Component of Chronic pain (NCCP) was screened with the DN4 questionnaire, and sleep was assessed with the Pittsburg questionnaire. Depression, anxiety, quality of life, and concomitant treatment were also evaluated. Results were expressed using effect sizes (ESs) and 95% confidence intervals. Results: Fifty new patients with a history of at least one fully documented fragility vertebral fracture (VF) or nonvertebral fracture (NVF) due to osteoporosis, in the last 2 years minus the previous 6 months, were included. Findings show that 21% patients with VF and 28% patients with NVF reported NCCP (DN ≥ 4). NCCP patients had more intense pain (NPRS = 5.1 ± 2.9 vs. 2.9 ± 2.7, ES = 0.82 [0.18; 1.44], p =0.019) and impaired sleep compared to patients without NCCP (ES = 0.71 [0.08; 1.33], p =0.043). A remarkable point was that patients had no specific oral or topical treatment for NCCP and were only taking on demand paracetamol and nonsteroidal anti-inflammatory drugs. Conclusions: Future research should focus on the neuropathic characteristics of pain patients with OP, in order to better manage OP-related pain., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Marie-Eva Pickering et al.)

Abstract: Experimental studies have suggested that nitrous oxide-induced analgesia depends on interactions with opioids. On the basis of these results, we hypothesized that the effects of inhaled nitrous oxide/oxygen (N 2 O/O 2 ) 50%-50% equimolar mixture (EMONO) on patients with neuropathic pain would be higher in those receiving concomitant opioids. To test this hypothesis, we did exploratory post hoc analyses of our recently published ProtoTOP study to compare the effects of EMONO and placebo in patients with or without concomitant opioid treatment. A total of 92 patients of the 221 (ie, 41.6%) included in the ProtoTOP study were concomitantly treated with opioids. In contrast with our previous analyses, average pain intensity was significantly decreased in comparison with placebo one week after the last treatment administration in patients treated with opioids, but not in those treated without opioid, and this effect was maintained over the 4-week follow-up period. Neuropathic pain symptom inventory (NPSI total and subscores) was also significantly more decreased after inhalation of EMONO in comparison with placebo only in patients receiving opioids. The proportion of patients with at least 30% pain reduction and of those reporting an overall improvement with the Patient Global Impression of Change were significantly higher only in this population of patients. In conclusion, these results complement our previous analyses with the identification of a specific population of responders to EMONO inhalation in patients with neuropathic pain. As suggested by experimental studies, we hypothesized that these long-lasting analgesic effects could depend on the anti-N-methyl-D-aspartate properties of N 2 O., (Copyright © 2022 International Association for the Study of Pain.)

Objective: To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application., Design: Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up., Blinding: Open-label., Setting: Multicenter clinical trial., Subjects: STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy., Methods: Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean "interference with sleep" score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment., Results: In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction., Conclusions: Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Objective: Peripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics., Methods: PNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g., drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis., Results: A total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender., Conclusions: This study highlights the need for accessible guidance for non-pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2020 International Association for the Study of Pain.)

Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or small-fibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and non-pharmacological treatments., Competing Interests: Competing interests: FB reports personal fees from Grünenthal, during the conduct of the study; personal fees from Lilly, Boston and Novartis, outside the submitted work; AC reports personal fees from Grunhental, outside the submitted work; PB reports personal fees from Grünenthal, during the conduct of the study; SP reports personal fees from Grünenthal, grants and personal fees from Sanofi and Pfizer, during the conduct of the study; TT reports personal fees from Grünenthal, during the conduct of the study; grants and personal fees from Amgen, Chugai, UCB, Pfizer, MSD and Novartis, personal fees from Gilead, Arrow, Biogen, BMS, Expanscience, Gilead, LCA, Lilly, Medac, Nordic, Sandoz, Sanofi, Theramex, Thuasne and TEVA, grants from Bone Therapeutics, outside the submitted work; TL reports personal fees from Grunenthal, Allergan, IPSEN and MERZ, outside the submitted work; LG reports personal fees from Grünenthal, during the conduct of the study; DW reports personal fees from Grünenthal, during the conduct of the study, personal fees from AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Celgene, Hospira, Lilly and Sandoz, outside the submitted work, indirect interests: AbbVie, Pfizer, Roche Chugai, MSD, UCB, Mylan, Fresenius Kabi. CD reports personal fees from Grünenthal, during the conduct of the study; A-PT reports personal fees from Menarini, personal fees from Recordati, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic postsurgical neuropathic pain (CPSNP) is frequent. While prevalence varies considerably according to type of operation and means of evaluation, it can reach 37% following breast surgery. Identification of risk factors related to the procedure and to the patient and taking into account the development of new, minimally invasive surgical techniques is increasingly nerve-sparing and reduces the likelihood of injury. CPSNP diagnosis in daily practice is facilitated by simple and quickly usable tools such as the NP4 4-question test. Management is based on pharmacological (analgesics, antiepileptics, antidepressants, local anesthetics) and non-pharmacological (kinesitherapy, neurostimulation, psychotherapy) approaches. In light of the present review of the literature, the authors, who constitute an expert group specialized in pain management, anesthesia and surgery, express their support for topical treatments (lidocaine, capsaicin) in treatment of localized postsurgical neuropathic pain in adults., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Patient-Reported Outcome (PRO) instruments have been developed to evaluate pain management in daily practice; the Patients' Global Impression of Change (PGIC) is particularly recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. The prospective non-interventional multicenter PRO-QURE study aimed at assessing correlations between PGIC and pain measurements and treatment effects in patients followed in French pain centres., Methods: Respectively, 495 and 379 patients with peripheral neuropathic pain initiating treatment with capsaicin 8% cutaneous patch(es) (female, 62.6%; mean age, 54.0 ± 14.8 years; post-surgical or traumatic pain, 52.7%; mean pain duration, 42.2 ± 54.1 months; DN4 score >4, 92.9%) completed the PGIC and several other PRO instruments before (baseline) and 3 months (M3) after treatment application., Results: At M3, improvement ("much improved" or "very much improved") was observed in 23.0% of patients, associated with decreases of -3.0 ± 2.2, -2.5 ± 2.4, and -23.1 ± 19.7 in BPI pain intensity, BPI pain interference and NPSI total scores, respectively. The highest Spearman's rank correlation coefficients with PGIC were found for pain intensity (BPI: r = -0.479, p < 0.001), satisfaction with current state (Patient Acceptable Symptomatic State: r = 0.455, p < 0.001), and treatment effectiveness (TSQM: r = 0.431, p < 0.001); correlation coefficients were lower for all NPSI scores, BPI pain interference score, HAD scores and EQ-5D-3L index., Conclusions: In daily clinical practice, significant improvement in peripheral neuropathic pain, as assessed by PGIC scores, significantly correlated with changes in well-established measures of pain intensity, pain interference with activities of daily living, mood and quality of life, confirming its clinical interest as PRO measure in real-world conditions., Significance: Clinically important improvement in peripheral neuropathic pain, as assessed by PGIC scores, significantly correlated with well-established measures of pain intensity, pain interference in daily life and treatment efficacy. This result, associated with the ease of administration and scoring, encourages the widespread use of the PGIC in daily practice., (© 2019 European Pain Federation - EFIC®.)

Objective: To describe the characteristics of patients treated with the capsaicin 8% patch, prescribing conditions, long-term effects of repeat treatment on pain intensity and perception, quality of life, and impact on concomitant medication., Methods: A national, longitudinal, prospective, non-interventional, post-marketing open study was conducted in 50 French pain centers. Adult volunteer non-diabetic patients with peripheral neuropathic pain receiving capsaicin 8% patch treatment were consecutively enrolled. Treatment could be repeated over a 12-month period, with 6 months' follow-up after last application., Results: A total of 684 patients (age: 53.0 ± 14.9 years, mean ± standard deviation; post-traumatic/surgical peripheral neuropathic pain: 76.3%; pain intensity: 6.2 ± 1.7; pain duration: 3.0 years, median) were treated with 1 to 5 patches at 3/4 month intervals; 70.3% were naive to capsaicin 8% patch treatment at inclusion. Six months after last application, treatment was considered as successful for 21.8% (95% confidence interval: 17.5%-26.7%) of patients by a stringent criterion combining improvement according to the patient's global impression of change (PGIC) and at least 30% improvement on a numerical pain rating scale (NPRS). Clinically relevant improvement in health-related quality of life was observed at end-of-study. No unexpected safety concerns were observed with capsaicin 8% patch repeat treatment., Conclusions: The data of this post-marketing study meets the request by the French authorities for additional data on conditions of use in everyday practice. They confirmed the tolerance and long-term effect of capsaicin 8% patch in patients with peripheral neuropathic pain in real-world conditions.

The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.

Cannabis-based medicines are being approved for pain management in an increasing number of European countries. There are uncertainties and controversies on the role and appropriate use of cannabis-based medicines for the management of chronic pain. EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper to empower and inform specialist and nonspecialist prescribers on appropriate use of cannabis-based medicines for chronic pain. The expert panel reviewed the available literature and harnessed the clinical experience to produce these series of recommendations. Therapy with cannabis-based medicines should only be considered by experienced clinicians as part of a multidisciplinary treatment and preferably as adjunctive medication if guideline-recommended first- and second-line therapies have not provided sufficient efficacy or tolerability. The quantity and quality of evidence are such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain. For all other chronic pain conditions (cancer, non-neuropathic noncancer pain), the use of cannabis-based medicines should be regarded as an individual therapeutic trial. Realistic goals of therapy have to be defined. All patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to reach the predefined goals and/or the patient is additionally burdened by an unacceptable level of adverse effects and/or there are signs of abuse and misuse of the drug by the patient, therapy with cannabis-based medicines should be terminated., Significance: This position paper provides expert recommendations for nonspecialist and specialist healthcare professionals in Europe, on the importance and the appropriate use of cannabis-based medicines as part of a multidisciplinary approach to pain management, in properly selected and supervised patients., (© 2018 European Pain Federation - EFIC®.)

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation., Significance: Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development., (© 2017 European Pain Federation - EFIC®.)

Purpose: The prevalence of neuropathic pain is high in the general population, and high priority is given to the management of this pain condition. The treatment of neuropathic pain remains challenging, despite the publication of national and international recommendations. The purpose of this narrative review of venlafaxine (VLX) is to provide a better knowledge of the pharmacology of this drug and a clearer view of its efficacy and tolerability in neuropathic pain., Methods: Two independent reviewers searched PubMed with the following search terms: serotonin and noradrenalin reuptake inhibitors OR VLX hydrochloride AND pain. The reviewers included all clinical studies that investigated VLX in neuropathic pain conditions and excluded animal studies, studies on fibromyalgia, studies that focused on the prevention of neuropathic pain, case reports, and studies that did not clearly describe neuropathic pain in the included patients. We describe the 13 studies that we analyzed., Findings: Eleven were randomized clinical trials, and the comparator was placebo in 8 studies. Nine studies reported that VLX was effective against neuropathic pain. However, among the trials, only one against placebo included a large number of patients with >200 participants and one against prégabaline and carbamazepine had >200 patients. Most of the adverse events reported in the selected studies were consistent with known adverse events of VLX, and most were mild to moderate. However, most studies were of very short duration., Implications: Most of the clinical studies found that VLX was effective and well tolerated. However, given the limited number of study and the limitations of all these studies, further large clinical trials are needed. Currently, considering the limited therapeutic options for treating neuropathic pain and the highly variable nature of responses to all drugs, VLX has a place as a treatment option for neuropathic pain., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Background: This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN)., Methods: Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function., Results: Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%)., Conclusion: In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone., Trial Registration: ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.

Sensory profiles are heterogeneous in neuropathic pain disorders, and subgroups of patients respond differently to treatment. To further explore this, patients in the COMBO-DN study were prospectively assessed by the Neuropathic Pain Symptom Inventory (NPSI) at baseline, after initial 8-week therapy with either duloxetine or pregabalin, and after subsequent 8-week combination/high-dose therapy. Exploratory post hoc cluster analyses were performed to identify and characterize potential subgroups through their scores in the NPSI items. In patients not responding to initial 60 mg/d duloxetine, adding 300 mg/d pregabalin for combination treatment was particularly effective regarding the dimensions pressing pain and evoked pain, whereas maximizing the duloxetine dose to 120 mg/d appeared more beneficial regarding paresthesia/dysesthesia. In contrast, adding 60 mg/d duloxetine to 300 mg/d pregabalin in case of nonresponse to initial pregabalin led to numerically higher decreases in all NPSI dimensions/items compared to maximizing the pregabalin dose to 600 mg/d. Cluster analysis revealed 3 patient clusters (defined by baseline scores for the 10 NPSI sensory items) with different pain profiles, not only in terms of overall pain severity, but also across NPSI items. Mean Brief Pain Inventory average pain improved in all clusters during combination/high-dose therapy. However, in patients with severe pain, the treatment effect showed a trend in favor of high-dose monotherapy, whereas combination therapy appeared to be more beneficial in patients with moderate and mild pain (not significant). These complementary exploratory analyses further endorse the idea that sensory phenotyping might lead to a more stratified treatment and potentially to personalized pain therapy., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Transcranial magnetic stimulation (TMS) is a non-invasive method for activating specific areas of the brain. There are two variants, repetitive TMS (rTMS) and direct TMS. Rapid changes in an electrical current induce a magnetic field, which in turn induces an electrical current in a nearby conductor. When a coil is positioned over the brain, rTMS delivers very brief and painless magnetic pulses to the brain. Initially, rTMS was developed as a treatment for depression. Since then, potential indications have been extended to the treatment of chronic pain, most notably in patients with rheumatic diseases. Thus, active research is being conducted into rTMS effects in fibromyalgia, chronic low back pain, and type I complex regional pain syndrome. Studies have established that rTMS is safe; provides pain relief, at least in the short-term; and improves the psychological correlates of chronic pain. These data support further development efforts with the goal of using rTMS in patients with chronic pain, including those with rheumatic diseases. French physicians have shown a high level of interest in rTMS, and the first French recommendations for using this method were issued in 2011. Further research is needed to determine the optimal stimulation parameters, session frequency, and session duration, as well as the best indications. Physicians who see many patients with chronic pain, such as rheumatologists, should be aware of this developing non-pharmacological and safe treatment modality, which can be of considerable help to their patients., (Copyright © 2013. Published by Elsevier SAS.)

Unlabelled: The present study investigated the neuropathic components of chronic low back pain (LBP) in patients with and without lower limb pain using the DN4 questionnaire and confirmed its psychometric properties. Patients (n = 132) from 11 French multidisciplinary pain or rheumatology centers were classified by a first investigator into 4 groups derived from the Quebec Task Force Classification of Spinal Disorders (QTFSD): group 1 (pain restricted to the lumbar area); group 2 (pain radiating proximally); group 3 (pain radiating below the knee without neurologic signs); and group 4 (pain radiating towards the foot in a dermatomal distribution, with neurological signs, corresponding to typical radiculopathy). A second investigator applied the DN4 questionnaire to the lower limb (groups 2 to 4) and lower back. A comparison of groups 1 and 4 confirmed the psychometric properties of DN4 (sensitivity 80%; specificity 92%, for a cutoff of 4/10, similar to other neuropathic conditions). In the lower limb, the proportion of patients with neuropathic pain (NP) was related to the distality of pain radiation (15, 39, and 80% in groups 2, 3 and 4, respectively; P < .0001). In the lower back, the proportion of patients with NP was higher for patients with typical radicular pain compared with the other groups (P = .006). Thus, typical radiculopathy has similar characteristics as other neuropathic conditions and is confirmed as the commonest neuropathic syndrome in LBP patients. The observation that neuropathic and nociceptive components of LBP vary in the back and lower limb probably accounts for the discrepancies of reported prevalence rates of NP in LBP. As this study was essentially based on a questionnaire, future studies combining standard clinical sensory testing, specific questionnaires, and more objective assessment of the sensory lesion are now required to further investigate the neuropathic component of chronic LBP., Perspective: This study confirms the psychometric properties of the DN4 questionnaire to assess neuropathic pain in patients with low back pain. Neuropathic mechanisms largely contribute to pain in the lower limb as compared to the back, but neuropathic pain is not restricted to typical radiculopathy. This may have significant implications for the choice of treatment strategy in these patients., (Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.)