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The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.

Objectives Neurological complications including pain are common after treatment for breast cancer. This prospective study investigated the symptoms, intensity and interference of chemotherapy-induced peripheral neuro-pathy. (CIPN) in the feet and hands compared to surgery- and radiation-induced neuropathy in the breast and upper arm. Methods Consecutive patients referred to surgery for breast cancer were included in a prospective study and completed a questionnaire at baseline and a follow-up questionnaire and interview after one year. CIPN was assessed with the CIPN20 questionnaire and the Michigan Neuropathy Screening Instrument questionnaire (MNSIq). Pain intensity was rated on a numeric rating scale (NRS, 0–10). Results In total 144 patients were included, of which 73 received chemotherapy. At one-year follow-up, symptoms of polyneuropathy were more common in patients treated with chemotherapy. Tingling or numbness in the feet in those treated/not treated with chemotherapy was reported by 44 (62%) and 15 (21%), respectively. Pain was present in 22 (30%) and 10 (14%), respectively. Pain in the area of surgery was reported by 66 (46%). Although less common, pain in the feet in those treated with chemotherapy was rated as more intense and with more daily life interference than pain in the surgical area (NRS 5.5 (SD 1.9) vs. 3.1 (SD 1.9). Conclusions Neurological complications including pain following surgery and chemotherapy represent a burden to breast cancer survivors. In those who had received chemotherapy, pain in the feet was less common than pain in the surgical area, but pain in the feet was more intense and had a higher interference with daily life. Our study emphasizes the need for either baseline data or a control population for improved estimation of the presence and severity of CIPN and pain from questionnaires.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP).METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP.RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases.CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

This chapter presents the case of a woman scheduled for total knee arthroplasty for osteoarthritis who has severe baseline anxiety, sleep disorders, catastrophizing, and depression and overuses opioids for migraine with chronic headache. This case illustrates the risk factors for chronic postsurgical pain, including neuropathic postsurgical pain. Risk factors include preoperative pain, postoperative pain, and opioid use but also many psychological factors, particularly state or trait anxiety, catastrophizing, and depression, as well as lack of cognitive flexibility. Patients with these risk factors should be carefully assessed, undergo psychotherapy before and/or after surgery, and be carefully managed for their pain as soon as possible after surgery to avoid long-term pain chronicization.

This chapter presents a case of a man with chronic sciatica and localized pain area at the leg who has not tolerated prior drug medications. Due to the necessity to maintain intellectual and professional activity because he is an active lawyer, transcutaneous electrical nerve stimulation (TENS) is a relevant therapeutic option. The efficacy of TENS has been shown (weak level) in peripheral neuropathic pain, the best indications being painful radiculopathy, painful neuropathies, and post-traumatic/postsurgical nerve lesions with circumscribed pain area. Safety and tolerability are excellent. TENS may also be used to conduct transcutaneous vagus nerve stimulation. TENS may be recommended as stand-alone therapy or add on to other treatments.

This chapter presents the case of an elderly woman who suffers from chronic bilateral pain in the tongue described as burning. Pain is moderately improved by chewing gum but is worse in the evening or after talking. Examination of the tongue is normal, and there is no apparent sensory deficit. Biological testing is normal. This case is compatible with primary burning mouth syndrome (BMS). Although BMS is not considered as neuropathic, it has many similarities with neuropathic pains in terms of symptoms and mechanisms. Guidelines for neuropathic pain may apply to BMS with emphasis on pregabalin, gabapentin, and duloxetine. Secondary causes include mainly candidosis. Treatment is difficult, with weak evidence for efficacy of topical clonazepam.

This chapter presents the case of a 52-year-old woman suffering from shoulder pain after mastectomy with lymph node dissection. However, her pain is not neuropathic but, rather, related to adhesive capsulitis. Pain is common after mastectomy and may be neuropathic or nociceptive. Patients who undergo breast cancer surgery, radiotherapy, and chemotherapy are at risk for several types of neuropathic pain, but nociceptive pain after mastectomy with or without radiotherapy is even more common. Particularly after a certain age, these patients may also have chronic pain independently of surgery or radiotherapy. It may be difficult to differentiate distinct pain mechanisms when several types of pains are present in the same neuroanatomical territory, and this may require screening questionnaires.

This chapter presents the case of a man operated on for lung cancer who has a unique bone cervical metastasis responsible for nociceptive pain at the neck responding to opioids and neuropathic pain with burning and innumerable pain paroxysms (electric shocks) at the arm, which are not alleviated by opioids. In this case, transmucosal fentanyl is not mandatory because pain paroxysms are innumerable and of neuropathic origin. In this context, it is advisable to introduce an antineuropathic drug, such as pregabalin or gabapentin, in combination with oral morphine. Neuropathic pain affects up to 40% of cancer patients and is associated with increased pain intensity, analgesic consumption, and decreased quality of life.

This chapter presents the case of a 48-year-old woman who was operated from L4–L5 left discal herniation and spinal stenosis. Despite surgery, she continues to suffer from chronic low back and neuropathic leg pain. Lumbar magnetic resonance imaging does not show any new pathological image of discal herniation. She has received acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and epidural corticosteroid infiltrations without any efficacy; does not tolerate weak opioids; and is afraid of moving. Physical reconditioning and psychological advice are recommended. Opioids should not be proposed as first line, and conventional analgesics and NSAIDs are generally ineffective; lumbar epidural steroid injections are controversial. For chronic neuropathic (radicular) pain, recommendations should follow general guidelines for peripheral neuropathic pain.

This chapter presents the case of a 58-year-old woman with a past history of smoking and type II diabetes necessitating insulin therapy who complains of pain in the lower limbs. Electromyography shows an axonal neuropathy of the lower limbs. However, her pain is not due to diabetic neuropathy but, rather, to severe peripheral arterial disease. This woman finally underwent surgical revascularization. Recovery was total, and duloxetine could be stopped. This case reminds that many patients with diabetic neuropathy have pain in the feet, but their pain is not necessarily related to their neuropathy, and other frequent causes include nociceptive pains due to ulcers, infections, bedsores, arthropathy, and peripheral arterial disease.

This chapter presents the case of an elderly woman who suffers from trigeminal neuropathy with severe facial pain secondary to brainstem lesion, refractory to first-, second-, and third-line treatments of neuropathic pain. In this case, noninvasive central brain stimulation may be considered in specialized centers. These techniques encompass repeated high-frequency (≥10 Hz) repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Their efficacy has been mainly established for motor cortex rTMS in peripheral and central refractory neuropathic pain. Best procedures include robot-assisted neuronavigation. Safety is good and main side effects include headache. The efficacy of tDCS of the motor cortex is less established for neuropathic pain.

This chapter presents the case of an elderly woman with intercostal postherpetic neuralgia with a well circumscribed and limited area of pain for whom topical agents are probably the best choice. These include U.S. Food and Drug Administration-approved daily use of 5% lidocaine plasters and capsaicin high-concentration patches every 3 months in specialized settings. Subcutaneous botulinum toxin A (off-label) may also be proposed by specialist use if pain is refractory. Topical agents are expected to have less efficacy if the pain is present in an area of total sensory loss. This case report illustrates that it is possible to combine several topical agents due to their distinct mechanisms and their different modalities of applications.

This chapter presents the case of a young man with spinal cord injury pain who does not respond to fluoxetine. Antidepressants and antiepileptics are the mainstay of therapy for neuropathic pain, but not all have the same efficacy. Effective antidepressants include tricyclic agents and drugs acting on the reuptake of serotonin and noradrenalin such as duloxetine, whereas selective serotonin reuptake inhibitor antidepressants are not effective. Antiepileptics effective in neuropathic pain mainly include gabapentin and pregabalin, whereas sodium channel blockers such as carbamazepine are mainly effective on trigeminal neuralgia. Antidepressants and antiepileptics may be combined at moderate dosages to optimize their efficacy without increasing side effects.

This chapter presents the case of a woman with occipital neuralgia and severe, paroxysmal, shooting pain who is refractory to conservative treatment, including nerve blocks and antineuropathic drugs. She is therefore a good candidate for peripheral nerve stimulation and, to a lesser extent, pulsed radiofrequency. The best potential indication for peripheral nerve stimulation is refractory peripheral neuropathic pain involving one nerve territory, although the level of evidence for efficacy remains low. Occipital nerve stimulation has been mainly studied in occipital neuralgia, migraine, and cluster headache. Pulsed radiofrequency works by delivering a targeted electrical field to the dorsal root ganglion and has been found effective mainly in thoracic postherpetic neuralgia and cervical radiculopathy, with a moderate quality of evidence.

This chapter presents the case of an 11-year-old girl with hip osteosarcoma invading the lumbar plexus who suffers from extreme neuropathic pain with tactile allodynia, which is not relieved by strong opioids. This case illustrates that neuropathic pain in children is often related to cancer. Osteosarcoma is the leading type of cancer in children. It may be responsible for neuropathic pain because of plexus lesion, or it may induce nociceptive pain due to bone lesion. Other causes of neuropathic pain in children and adolescents include complex regional pain syndrome, cancer, Guillain–Barré syndrome, spinal cord injury, nerve trauma, and genetic conditions. Treatment of neuropathic pain in children is mainly based on gabapentin.

This chapter presents the case of a 58-year-old man with phantom limb pain after mid-thigh amputation. The amputation occurred after he stepped on a land mine in Cambodia when he was 23 years old. His pain is described as electric shocks and stabbing. He wears a prosthetic leg. Pain was poorly responsive to oral drug therapy for neuropathic pain and finally responded to mirror therapy. Many patients experience phantom limb pain after amputation. Conventional therapeutic approaches are similar to those of other neuropathic pains, but specific therapeutic approaches include mirror therapy, virtual reality, proprioceptive training, and prosthetic use with somatosensory input.

This chapter presents the case of a 32-year-old man who suffers from persisting neuropathic groin pain after surgery for left inguinal hernia (open surgery). Examination of the painful area discloses mild sensory deficit, allodynia to brush as well as red skin and swelling. Because he did not want to receive oral medications, he was treated by topical agents. Postsurgical pain is commonly neuropathic, with common causes being hernia repair but also thoracotomy, mastectomy, knee/hip replacement, cholecystectomy, and varicose vein stripping. Management is similar to that of other peripheral neuropathic pains, but topical treatments should be preferred if the area of pain is small.

This chapter presents the case of a 48-year-old man with type II diabetes and alcoholism who reports bilateral and symmetrical at both feet described as neuropathic. Blood tests show chronic hepatitis. He satisfies criteria for diabetic and/or alcoholic painful neuropathy. Diabetic painful neuropathy affects 15–35% of patients with diabetes and is more prevalent in type II diabetes. Risks may be enhanced by alcohol. Initial management focuses on glycemic control and lifestyle measures, whereas neuropathic pain requires specific antineuropathic treatments. Since this patient had contraindications or did not tolerate first line recommended drugs for painful diabetic neuropathies (e.g., duloxetine, gabapentin, pregabalin) and his pain area was limited and well circumscribed, second line topical treatments including off label 5% lidocaine plasters (US Food and Drug Administration and European Medical Agency approved for postherpetic neuralgia) and high-concentration capsaicin patches (US Food and Drug Administration approved for diabetic painful neuropathies and postherpetic neuralgia) were proposed.

This chapter presents the case of a patient with chronic postsurgical pain who has serious psychiatric comorbidity, which contributes to enhance his pain and disability, reduce his coping abilities, and reduce the chance of therapeutic success. This case illustrates the importance of detecting psychiatric comorbidities in patients with neuropathic pain and working in close collaboration with psychologists and psychiatrists. Neuropathic pain tends to impair quality of life more than any other type of pain and is often associated with disability, anxiety, depression, disturbed sleep, or catastrophizing. Questionnaires may be helpful in identifying these PROs. The management of psychiatric comorbidities should precede or be associated with the management of pain.

This chapter presents the case of a woman who suffers from central pain associated with multiple sclerosis. Pain is paroxysmal with very severe and frequent electric shocks. She smokes cannabis to relieve her pain paroxysms but has no signs of craving. She appears to be a good candidate for oral or sublingual cannabinoids (oral tetrahydrocannabinol or nabiximols). Contrary to painful spasticity, the efficacy of cannabinoids is still unclear in neuropathic pain based on randomized controlled trials, but a subgroup of patients may likely benefit from these drugs, which seem to be more effective on pain paroxysms. Cannabinoids have been more studied in neuropathic pain than in other types of chronic pain.

This chapter presents the case of a woman with postsurgical neuropathic pain who is suffering considerably because of multiple life events, social isolation, and anxiety. Psychological therapy plays a major role in the management of chronic neuropathic pain. It aims to decrease dysfunctional coping strategies, thoughts about pain, and catastrophizing, which are common consequences of chronic pain, and improve anxiety and mood. Cognitive–behavioral therapy has been the most studied. Psychotherapies may be recommended as stand-alone or add on to other treatments. Best candidates should be motivated and educated subjects, with maladaptive thoughts about their neuropathic pain and/or mood or anxiety disorders.

This chapter presents the case of a young patient with T10 paraplegia who suffers from several types of pain: neuropathic below-level pain at the lower limbs; musculoskeletal pain at the shoulder; and lower pain, visceral abdominal pain, and peripheral neuropathic pain due to ulnar compression at the upper limbs. Pain after spinal cord injury (SCI) is frequent and is often neuropathic, but other types of pain often coexist. Screening questionnaires are helpful to discriminate neuropathic SCI pains from other types of pain. Management should be multimodal and depend on pain mechanisms. For below-level neuropathic pain, oral antineuropathic drugs and physical therapies may be proposed. For at-level or above-level SCI, additional treatments may include topical agents and transcutaneous electrical nerve stimulation.

This chapter presents the case of a man who suffers from chronic back and leg pain despite spinal surgery, generally referred to as failed back surgery syndrome. Because his pain did not respond to drug medications and was predominantly neuropathic, he appears to be a good candidate for spinal cord stimulation. The latter has been mainly studied in failed back surgery syndrome, with best candidates being those with predominant radicular pain, in complex regional pain syndrome, and in diabetic painful neuropathy. Decisions should be taken after pluriprofessional assessment, including advice from a psychologist or a psychiatrist. Newer technologies include high- to very high-frequency stimulations of generally short duration and low amplitude, burst stimulation, and dorsal root ganglion stimulation.

This chapter presents a case of a young woman who suffers from chronic orofacial pain, which appeared after left mandibular third molar avulsion. Pain is continuous, described as hot/burning and aching, without pain paroxysms and involving the whole hemiface. Clinical examination is normal. This case is compatible with persistent idiopathic orofacial pain (formerly atypical facial pain), which may be triggered by minor trauma or surgery particularly involving the dental nerves. There is a continuum between idiopathic orofacial pain and post-traumatic trigeminal neuropathic pain. The management is similar to that of peripheral neuropathic pain and includes psychological therapy because this pain is often associated with psychological or psychiatric comorbidities.

A 66-year-old man with type II diabetes suffers from lower limb pain mainly described as burning, electric shocks, associated with tingling and pins, needles and numbness. On examination, there is thermoalgesic deficit and allodynia to brush, but no motor impairment or abnormal reflexes. Pain is not relieved by acetaminophen 3 g per day. To complete the diagnostic workup, it is mandatory to assess the link between pain onset and diabetes, determine the exact pain area, assess the quality of pain, and complete the clinical examination. The initial detection of neuropathic pain in primary care may be assessed with screening questionnaires such as the DN4, the LANSS, and PainDETECT.

This chapter presents the case of a patient with traumatic spinal cord injury responsible for at-level allodynia and below-level spontaneous pain who is totally refractory to first-, second-, and third-line treatments, including noninvasive brain neurostimulation. He is a good candidate for invasive treatments, after multidisciplinary assessment. Because spinal cord stimulation is difficult due to his spinal cord lesion, invasive therapeutic options include intrathecal analgesic therapy or central invasive neurostimulation. Drugs officially labeled by the U.S. Food and Drug Administration for intrathecal administration include morphine, ziconotide, and baclofen. Trialing and small initial dosages are recommended. Motor cortex stimulation involves the placement of electrodes along the surface of the brain in the precentral gyrus, corresponding to the motor cortex area. The level of evidence regarding the efficacy of deep brain stimulation remains inconclusive in neuropathic pain.

This chapter discusses the case of a man with postherpetic neuralgia who presents with multiple neuropathic symptoms, such as burning pain, electric shocks, and allodynia, and has difficulty rating his average pain intensity on a simple scale. Hence, he has difficulty reporting the efficacy of drug treatments, with a contradiction between his apparently constant pain intensity and his improved disability. This case shows the potential relevance of specific neuropathic pain questionnaires even in routine use to facilitate treatment adaptation. Most treatments of neuropathic pain have an incomplete effect on pain symptoms. Thus, the use of specific neuropathic assessment questionnaires in routine may facilitate treatment adaptation.

This chapter presents the case of a man who suffers from severe neuropathic pain due to cauda equina syndrome refractory to well-conducted treatments without psychiatric comorbidity. For this patient, invasive therapy may be considered. These techniques should only be considered after multidisciplinary evaluation including psychological assessment. Best candidates are patients with regional neuropathic pain. The choice of treatment depends on the clinical context, the origin of pain, and the area of pain. By far the most documented invasive therapy for neuropathic noncancer pain is spinal cord stimulation. Other invasive techniques include peripheral nerve stimulation or pulsed radiofrequency (minimally invasive), deep brain/epidural motor cortex stimulation, intrathecal therapy, and ablation surgery techniques in select conditions.

This chapter presents the case of a woman with severe complex regional pain syndrome CRPS for whom physiotherapy should be implemented as part of multimodal management. It may be beneficial for motor deficit or neglect, major sensory deafferentation, physical deconditioning, and fear of pain and movement. Because physical exercises may be initially very painful, strong analgesics may be proposed before each exercise to facilitate rehabilitation. Physiotherapy includes a large variety of interventions, particularly manual therapy, therapeutic exercises including physical reconditioning, electrotherapy (e.g., transcutaneous electrical nerve stimulation), and sensorimotor rehabilitation strategies including mirror therapy and graded motor imagery. Virtual reality is increasingly investigated for the treatment of acute pain, but there are limited data regarding its efficacy on neuropathic pain.

This chapter presents the case of a 68-year-old woman who has diabetic painful sensory neuropathy, a frequent cause of neuropathic pain. She has used acetaminophen, paracetamol, codeine, and ibuprofen without any efficacy. Duloxetine was proposed and had acceptable efficacy. Neuropathic pain does not respond to conventional analgesics and therapeutic management is minimally dependent on the aetiology of pain. Recommended first line drugs for neuropathic pain in primary care include serotonin and norepinephrine reuptake inhibitors (particularly duloxetine), tricyclic antidepressants (such as amitriptyline), gabapentin and, pregabalin. These drugs should be proposed as monotherapy first under the principle of individual titration (increase the doses up to side effects or efficacy) and should not be discontinued abruptly.

This chapter presents the case of a woman who initially developed pain involving the lower limbs, compatible with sensory neuropathy (specifically small fiber neuropathy), and now reports pain “all over the body,” associated with multiple other symptoms, fulfilling criteria for fibromyalgia. Fibromyalgia may classically develop in the context of rheumatological diseases, such as chronic arthritis or spondylosis, but also in relation with stress, sleep disorders, past traumatic events, or any focal painful injury. Fibromyalgia may also be associated with painful (small fiber) neuropathy, but it is unclear whether the neuropathy is a trigger or may cause the pain and associated symptoms in fibromyalgia syndrome. Therapeutic management should be based on the clinical phenotype and include mainly therapeutic education, physical reconditioning, and cognitive–behavior therapy.

This chapter presents the case of a man who reports chronic perineal pain, described as neuropathic (burning and stabbing), which started after intensive horseback riding and cycling. Pain involves the right genitals only, is increased by sitting, and is alleviated by standing. This is characteristic pudendal entrapment syndrome (Alcock syndrome), the most common cause of pudendal neuralgia. Management is difficult, and there are no international guidelines. Pudendal neuralgia corresponds to a peripheral neuropathic pain and as such may necessitate similar antineuropathic drugs as other neuropathic pains. Pudendal nerve blocks may have a diagnostic value in this context, and they may sometimes induce long-term benefit.

Neuropathic pain is a much more common pain disorder than usually thought, affecting up 10% of the general population worldwide. It encompasses a large number of conditions, such as sciatica, postsurgical pain, painful neuropathies, postherpetic neuralgia, multiple sclerosis, spinal cord injury, and stroke. However, neuropathic pain is still considered by many doctors as difficult to detect and extremely complex to manage. This book provides essential skills for the management of neuropathic pain. Each chapter presents case vignettes inspired by real patients, covering distinct aspects of neuropathic pain from common conditions such as sciatica to rare disorders such as erythromelalgia, but clinical cases sharing similarities with neuropathic pain, such as fibromyalgia or orofacial pain, are also covered. This book will help train unfamiliar physicians to use screening questionnaires; assess neuropathic pain and its causes; and manage patients with non-opioid analgesics, complementary medicine, psychotherapies, neuromodulation, or invasive techniques. To help readers gradually increase their skills, the book is arranged in three sections: Section 1 covers clinical cases often encountered in primary care, Section 2 addresses best therapeutic management, and Section 3 presents assessment and management of more complex cases. Medical students and doctors interested in pain management, from primary care physicians to specialists, should find this book practical, easy to read, and useful for everyday practice.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat neuropathic pain but the quality of evidence remains low. We aimed to assess the efficacy and safety of neuronavigated rTMS to the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in neuropathic pain over 25 weeks. We carried out a randomized double-blind, placebo-controlled trial at four outpatient clinics in France. Patients aged 18–75 years with peripheral neuropathic pain were randomly assigned at a 1:1 ratio to M1 or DLPFC-rTMS and rerandomized at a 2:1 ratio to active or sham-rTMS (10 Hz, 3000 pulses/session, 15 sessions over 22 weeks). Patients and investigators were blind to treatment allocation. The primary end point was the comparison between active M1-rTMS, active DLPCF-rTMS and sham-rTMS for the change over the course of 25 weeks (Group × Time interaction) in average pain intensity (from 0 no pain to 10 maximal pain) on the Brief Pain Inventory, using a mixed model repeated measures analysis in patients who received at least one rTMS session (modified intention-to-treat population). Secondary outcomes included other measures of pain intensity and relief, sensory and affective dimensions of pain, quality of pain, self-reported pain intensity and fatigue (patients diary), Patient and Clinician Global Impression of Change (PGIC, CGIC), quality of life, sleep, mood and catastrophizing. This study is registered with ClinicalTrials.gov NCT02010281. A total of 152 patients were randomized and 149 received treatment (49 for M1; 52 for DLPFC; 48 for sham). M1-rTMS reduced pain intensity versus sham-rTMS (estimate for Group × Session interaction: −0.048 ± 0.02; 95% CI: −0.09 to −0.01; P = 0.01). DLPFC-rTMS was not better than sham (estimate: −0.003 ± 0.01; 95% CI: −0.04 to 0.03, P = 0.9). M1-rRMS, but not DLPFC-rTMS, was also superior to sham-rTMS on pain relief, sensory dimension of pain, self-reported pain intensity and fatigue, PGIC and CGIC. There were no effects on quality of pain, mood, sleep and quality of life as all groups improved similarly over time. Headache was the most common side effect and occurred in 17 (34.7%), 23 (44.2%) and 13 (27.1%) patients from M1, DLPFC and sham groups, respectively (P = 0.2). Our results support the clinical relevance of M1-rTMS, but not of DLPFC-rTMS, for peripheral neuropathic pain with an excellent safety profile.

Spinal cord injury pain encompasses musculoskeletal and neuropathic pain. Its management is often multidisciplinary and involves specific drugs such as antidepressants and antiepileptics, and nonpharmacological treatment including psychotherapy, physical therapy and neuromodulation techniques. Recent progress in the diagnosis, assessment, and understanding of its mechanisms offers the perspective of a more rational therapeutic management, which should result in better therapeutic outcome.

International audience; Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management. Copyright

Les douleurs neuropathiques (DN) restent très difficiles à soulager. Plusieurs recommandations ont été proposées au cours de ces dernières années, mais aucune n’a pris en compte à ce jour l’ensemble des approches thérapeutiques disponibles. Nous avons réalisé une revue systématique portant sur toutes les études concernant le traitement des DN périphériques et centrales de l’adulte et de l’enfant, publiées jusqu’en janvier 2018 et avons évalué la qualité des études et le niveau de preuve des traitements au moyen du système GRADE. Les principaux critères d’inclusion étaient l’existence d’une DN chronique (≥ 3 mois), une méthodologie contrôlée et randomisée, un suivi supérieur ou égal à trois semaines, un nombre de patients supérieur ou égal à dix par groupe et une évaluation en double insu pour les traitements pharmacologiques. Sur la base du GRADE, nous recommandons en première intention les antidépresseurs inhibiteurs mixtes de recapture des monoamines (duloxétine et venlafaxine), les antidépresseurs tricycliques, la gabapentine pour toute DN, et les emplâtres de lidocaïne 5 % et la stimulation électrique transcutanée pour les DN périphériques localisées. Nous recommandons en deuxième intention la prégabaline, le tramadol (avec les précautions d’emploi afférentes aux opioïdes) et certaines associations pharmacologiques (antidépresseurs et gabapentine ou prégabaline) pour toute DN, et les patchs de haute concentration de capsaïcine (8 %) et la toxine botulique de type A (en milieu spécialisé) pour les DN périphériques localisées. Nous recommandons en troisième intention la stimulation magnétique transcrânienne répétitive à haute fréquence du cortex moteur (en milieu spécialisé) et les opioïdes forts (en l’absence d’alternative et en respectant les précautions d’emploi afférentes aux opioïdes) pour toute douleur neuropathique, et la stimulation médullaire pour les douleurs radiculaires chroniques postchirurgicales et la polyneuropathie diabétique douloureuse. La psychothérapie (thérapie cognitivocomportementale et thérapie de pleine conscience) peut être recommandée en deuxième intention en association avec les traitements précédents.

Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.