Characterization of Hyperacute Neuropathic Pain after Spinal Cord Injury: A Prospective Study.

There is currently a lack of information regarding neuropathic pain in the very early stages of spinal cord injury (SCI). In the present study, neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) for the patient's worst pain within the first 5 days of injury (i.e., hyperacute) and on follow-up at 3, 6, and 12 months. Within the hyperacute time frame (i.e., 5 days), at- and below-level neuropathic pain were reported as the worst pain in 23% (n = 18) and 5% (n = 4) of individuals with SCI, respectively. Compared to the neuropathic pain observed in this hyperacute setting, late presenting neuropathic pain was characterized by more intense painful electrical and cold sensations, but less itching sensations. Phenotypic differences between acute and late neuropathic pain support the incorporation of timing into a mechanism-based classification of neuropathic pain after SCI. The diagnosis of acute neuropathic pain after SCI is challenged by the presence of nociceptive and neuropathic pains, with the former potentially masking the latter. This may lead to an underestimation of the incidence of neuropathic pain during the very early, hyperacute time points post-injury. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01279811) PERSPECTIVE: This article presents distinct pain phenotypes of hyperacute and late presenting neuropathic pain after spinal cord injury and highlights the challenges of pain assessments in the acute phase after injury. This information may be relevant to clinical trial design and broaden our understanding of neuropathic pain mechanisms after spinal cord injury.

Nerve Pain after Burn Injury: A Proposed Etiology-Based Classification.

BACKGROUND: Understanding the mechanism of nerve injury may facilitate managing burn-related nerve pain. This proposed classification, based on cause of nerve injury, was developed to enhance the understanding and management of burn-related nerve pain. METHODS: This retrospective investigation included patients aged 15 years or older admitted to the burn center from 2014 to 2019. Burn-related nerve pain was patient-reported and clinically assessed as pain 6 months or more after burn injury, unrelated to preexisting illnesses/medications. The pain classification consisted of direct nerve injury, nerve compression, electrical injury, and nerve dysfunction secondary to systemic injury. The four categories were statistically analyzed between groups, using 52 variables. RESULTS: Of the 1880 consecutive burn patients, 113 developed burn-related nerve pain and were eligible for validation of the classification: direct nerve injury, n = 47; nerve compression, n = 12; electrical injury, n = 7; and nerve dysfunction secondary to systemic injury, n = 47. Factors, significantly increased, that distinguished one category from another were as follows: for direct nerve injury, continuous symptoms (p < 0.001), refractory nerve release response (p < 0.001), nerve repair (p < 0.001), and pruritus (p < 0.001); for nerve compression, Tinel signs (p < 0.001), shooting pain (p < 0.001), numbness (p = 0.003), intermittent symptoms (p < 0.001), increased percentage total body surface area burned (p = 0.019), surgical procedures (p < 0.001), and nerve release (p < 0.001); and for electrical injury, Tinel sign (p < 0.001), intermittent symptoms (p = 0.002), amputations (p = 0.002), fasciotomies (p < 0.001), and nerve release (p < 0.001). Nerve dysfunction secondary to systemic injury was distinguished by significantly less Tinel signs (p < 0.001), shooting pain (p < 0.001), numbness and tingling (p < 0.001), pruritus (p < 0.001), fascial excision (p = 0.004), skin grafts (p < 0.001), amputation (p = 0.004), nerve releases (p < 0.001), and third-degree burns (p = 0.002). CONCLUSION: A classification consisting of direct nerve injury, nerve compression, electrical injury, and nerve dysfunction secondary to systemic injury is presented that may guide patient management and research methods, with the goal of improving pain outcomes in burn-related nerve pain.

Transcranial Direct Current Stimulation and Visual Illusion Effect According to Sensory Phenotypes in Patients With Spinal Cord Injury and Neuropathic Pain.

Treatment of neuropathic pain (NP) in patients with spinal cord injury (SCI) remains a major challenge. The aim of the present study is to investigate if the effect of transcranial direct current stimulation combined with visual illusion, following a previously published protocol, has differential effects on pain-related sensory symptoms according to sensory phenotypes profiles. One hundred and thirty SCI patients with NP participated in this open-label trial. Sixty-five patients were given a daily 20-minutes combined treatment of transcranial direct current stimulation and visual illusion for 2 weeks. Sixty-five patients served as a control group. Clinical assessment was performed before and 2 weeks later, by using Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory, and Patient Health Questionnaire-9. There was significant improvement in the combined treatment group according to NPSI, Brief Pain Inventory, and Patient Health Questionnaire-9, but no changes in the control group. Following a cluster analysis of NPSI items at baseline assessment, 5 subgroups of patients with different pain-related characteristics were identified among the treated group, although differences between clusters were not significant. There was also improvement in mood, sleep quality, and enjoyment of life in the treated group. Despite a reduction of NP with the combined treatment, the analysis of sensory phenotype pain profiles does not provide a predictive value regarding the analgesic results of this combined neuromodulatory treatment. PERSPECTIVE: In this article we confirm the analgesic effect of a combined neuromodulatory therapy, transcranial direct current stimulation associated with visual illusion in patients with NP after an SCI. We have identified 5 clusters of NP with distinct sensory phenotypes, but there was not any specific sensory phenotype cluster that significantly responded to the combined therapy better than the other.

A Historical Review of Headaches: Who First Described Them and When did This Occur?

BACKGROUND: Headache is as old as human history and has been able to report, and the first descriptions were found in Greece and Mesopotamia. OBJECTIVE: Our objective was to know the date of the first description of ICHD-3 headaches, with their respective author. METHODS: We searched for articles that addressed the historical aspects of primary and secondary headaches and painful cranial neuropathies. RESULTS: Twenty-seven different headaches were analyzed according to the occurrence of their first description, with the respective author and country of origin. CONCLUSIONS: The knowledge of the first description of ICHD-3 headaches, with their respective author, showed us how and when the different headaches appeared over the years.

[Basic Knowledge of Drug Pain Therapy in the Palliative Situation]. / Basiswissen zur medikamentösen Schmerztherapie in der Palliativsituation.

This review provides an overview of the basic knowledge of drug pain therapy in the palliative situation. Pain is one of the main symptoms in 60 to 90 % of cancer patients. Pain also develops with neurological and other diseases that occur in end-of-life situations. To address this symptom, a holistic strategy is required that encompasses all physical, psychological, social, and spiritual aspects of the multi-dimensional pain experience ("total pain" concept).Drug treatment for cancer pain has been based on a stepwise approach for many years, starting with non-opioid analgesics, followed by moderate and strong opioids. In contrast, today's pain management is determined more by the actual intensity of this aversive event.The pain assessment should be tailored to identify a nociceptive vs. neuropathic pain component that needs to be challenged by the most appropriate drug therapies. Non-opioid analgesics are ideal substances for relieving nociceptive pain. Antidepressants and anticonvulsants reduce the intensity of new neuropathic pain. Opioids are suitable for all types of pain, but are restricted to a second line choice. Among all opioids are tilidine and tramadol prodrugs, which only relieve pain after activation in the liver. Drug-drug interactions may also block this activation. Rapid release opioids should be used for cancer breakthrough pain. Transdermal opioid applications are recommended for swallowing disorders, but usually not to initiate pain control. An opioid switch can be performed if side effects such as hallucinations for the selected opioid are more pronounced than the pain reduction.

Challenges of neuropathic pain: focus on diabetic neuropathy.

Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.

Therapeutic Approaches for Peripheral and Central Neuropathic Pain.

Neuropathic pain is a chronic secondary pain condition, which is a consequence of peripheral or central nervous (somatosensory) system lesions or diseases. It is a devastating condition, which affects around 7% of the general population. Numerous etiological factors contribute to the development of chronic neuropathic pain. It can originate from the peripheral part of the nervous system such as in the case of trigeminal or postherpetic neuralgia, peripheral nerve injury, painful polyneuropathies, or radiculopathies. Central chronic neuropathic pain can develop as a result of spinal cord or brain injury, stroke, or multiple sclerosis. As first-line pharmacological treatment options, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids are recommended. In trigeminal neuralgia, carbamazepine and oxcarbazepine are the first-choice drugs. In drug-refractory cases, interventional, physical, and psychological therapies are available. This review was structured based on a PubMed search of papers published in the field from 2010 until May 2019.

A Delphi consensus statement of the Neuropathic Pain Special Interest Group of the Italian Neurological Society on pharmacoresistant neuropathic pain.

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when "the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose." Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.

Psychological factors can cause false pain classification on painDETECT.

Background and aims The painDETECT questionnaire (PD-Q) has been widely used as a screening tool for the identification of neuropathic pain (NeP) as well as a tool for the characterization of patients' pain profile. In contrast to other NeP screening tools, the PD-Q is the only screening tool with weighted sensory descriptors. It is possible that responses to the PD-Q sensory descriptors are influenced by psychological factors, such as catastrophizing or anxiety, which potentially might contribute to an overall higher score of PD-Q and a false positive identification of NeP. This study aimed to explore (i) the relationship between psychological factors (catastrophizing, anxiety, depression and stress) and the total PD-Q score and (ii) if psychological factors are associated with false positive identifications of NeP on the PD-Q compared to clinically diagnosed NeP. Methods The study was a retrospective review of 1,101 patients attending an outpatient pain centre. Patients were asked to complete the PD-Q, the Pain Catastrophizing Scale (PCS), the Depression, Anxiety and Stress Scale (DASS) and the Brief Pain Inventory (BPI). For patients who were identified by PD-Q as having NeP, their medical records were reviewed to establish if they had a clinical diagnosis of NeP. Results Accounting for missing data, complete datasets of 652 patients (mean age 51 (SD14) years, range 18-88; 57% females) were available for analysis. Based on PD-Q scoring, NeP was likely present in 285 (44%) patients. Depression, anxiety, stress, catastrophizing, BPI pain and BPI interference were all significantly related to each other (p < 0.0001) and patients displaying these traits were significantly more likely to have a positive PD-Q score (p < 0.0001). For patients classified by PD-Q as having NeP, only 50% of patients had a clinical diagnosis of NeP. Anxiety was significantly associated with a false positive classification of NeP on PD-Q (p = 0.0036). Conclusions Our retrospective study showed that psychological factors including catastrophizing, depression, anxiety, and stress were all influential in producing a higher score on the PD-Q. We observed a high rate of false positive NeP classification which was associated with the presence of anxiety. Implications Clinicians and researchers should be aware that a patient's psychological state may influence the responses to PD-Q and consequently the final PD-Q score and its NeP classification.

Neuropathic pain: Definition, assessment and epidemiology.

Neuropathic pain has been a very active and productive clinical research field over the last 15 years. Studies have concerned multiple aspects of these complex chronic pain syndromes including their very definition, the elaboration of new diagnostic algorithms, the development of specific tools for their screening and measurement and their epidemiology. In this review, we summarize these recent evolutions that have impacted the way these pain syndromes are conceptualized and managed both in daily practice and in the clinical research setting.

Prevalence of Persistent Pain after Total Knee Arthroplasty and the Impact of Neuropathic Pain.

The present study aimed to define the prevalence of pain persisting after total knee arthroplasty (TKA) and determine the impact of neuropathic pain. Knee pain after TKA was evaluated in 154 patients (222 knees with osteoarthritis) using a numerical rating scale (NRS) and followed up for a mean of 4.7 years. The patients were classified according to whether they had no or mild pain (NRS ≤ 3), or moderate-to-severe pain (NRS > 3), and then assigned to groups with nociceptive, unclear, or neuropathic pain based on responses to painDETECT questionnaires. Risk factors for these types of pain were determined. The ratio of patients with moderate-to-severe pain was 28% (62 knees). Thirteen patients (21 knees; 9%) experienced unclear pain. Patients with moderate-to-severe or unclear pain had malalignment and lower Knee Society knee scores. In conclusion, a significant number of patients experienced moderate-to-severe and unclear pain after TKA. Moderate-to-severe pain was associated with unclear pain.

AAPT Diagnostic Criteria for Peripheral Neuropathic Pain: Focal and Segmental Disorders.

Peripheral neuropathic pain is among the most prevalent types of neuropathic pain. No comprehensive peripheral neuropathic pain classification system that incorporates contemporary clinical, diagnostic, biological, and psychological information exists. To address this need, this article covers the taxonomy for 4 focal or segmental peripheral neuropathic pain disorders, as part of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership and the American Pain Society (APS) collaborative to develop a standardized, evidence-based taxonomy initiative: the ACTTION-APS Pain Taxonomy (AAPT). The disorders-postherpetic neuralgia, persistent posttraumatic neuropathic pain, complex regional pain disorder, and trigeminal neuralgia-were selected because of their clinical and clinical research relevance. The multidimensional features of the taxonomy are suitable for clinical trials and can also facilitate hypothesis-driven case-control and cohort epidemiologic studies. PERSPECTIVE: The AAPT peripheral neuropathic pain taxonomy subdivides the peripheral neuropathic pain disorders into those that are generalized and symmetric and those that are focal or segmental and asymmetric. In this article, we cover the focal and segmental disorders: postherpetic neuralgia, persistent posttraumatic neuropathic pain, complex regional pain disorder, and trigeminal neuralgia. The taxonomy is evidence-based and multidimensional, with the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical and psychiatric comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.

The IASP classification of chronic pain for ICD-11: chronic neuropathic pain.

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.

Characteristics of neuropathic pain in individuals with chronic spinal cord injury.

OBJECTIVE: To present the characteristics of neuropathic pain in individuals with chronic spinal cord injury (SCI). METHODS: We recruited all individuals with chronic SCI referred to the Brain and Spine Injury Research center with a diagnosis of neuropathic pain from April 2013 to September 2015 into this historical cohort study. RESULTS: Forty individuals with chronic SCI-induced neuropathic pain entered this study with a mean age of 43.67+/-13.12 years and a majority of who were male (n=30, 75%). Motor vehicle collision (n=25, 62.5%) and fall (n=7, 17.5%) were the most common causes of SCI in our participants. There were 13 (32.5%) cervical, twenty (50%) thoracic, and 7 (17.5%) lumbosacral SCI. The mean `maximal pain intensity`, `overall pain intensity during the past week`, and `the pain intensity at the initial consultation in pain clinic` measured by numerical rating scale (NRS) in this cohort were 8.71+/-1.73, 6.32+/-1.60, and 6.11+/-2.48, respectively. Burning pain was the most frequently used description of pain reported by our participants. Pain intensity significantly decreased after six months of treatment for all three above categories. CONCLUSION: This study provides characteristics of neuropathic pain in a group of individuals with chronic SCI. Further large prospective studies are needed to determine the association between lesion level, completeness of injury, and region of pain.

Stratification of neuropathic pain patients: the road to mechanism-based therapy?

PURPOSE OF REVIEW: It has been demonstrated that within one pain entity, patients may report highly heterogenic sensory signs and symptoms. Although mechanism might differ fundamentally between those patients, yet the treatment recommendations are uniform throughout all phenotypes. Therefore, the introduction of new stratification tools could pave the way to an individualized pain treatment. RECENT FINDINGS: In the past, retrospective stratifications of patients successfully identified responders to certain pharmacological treatments. This indicated predictive validity and reliability of this classification tool in those patient subgroups. Further on, these observations have been confirmed in prospective studies. SUMMARY: This review focusses on recent achievements in neuropathic pain and suggests a promising implementation of an individualized pharmacological therapy in the future.

Prediction of central neuropathic pain in spinal cord injury based on EEG classifier.

OBJECTIVES: To create a classifier based on electroencephalography (EEG) to identify spinal cord injured (SCI) participants at risk of developing central neuropathic pain (CNP) by comparing them with patients who had already developed pain and with able bodied controls. METHODS: Multichannel EEG was recorded in the relaxed eyes opened and eyes closed states in 10 able bodied participants and 31 subacute SCI participants (11 with CNP, 10 without NP and 10 who later developed pain within 6 months of the EEG recording). Up to nine EEG band power features were classified using linear and non-linear classifiers. RESULTS: Three classifiers (artificial neural networks ANN, support vector machine SVM and linear discriminant analysis LDA) achieved similar average performances, higher than 85% on a full set of features identifying patients at risk of developing pain and achieved comparably high performance classifying between other groups. With only 10 channels, LDA and ANN achieved 86% and 83% accuracy respectively, identifying patients at risk of developing CNP. CONCLUSION: Transferable learning classifier can detect patients at risk of developing CNP. EEG markers of pain appear before its physical symptoms. Simple and complex classifiers have comparable performance. SIGNIFICANCE: Identify patients to receive prophylaxic treatment of CNP.

A Canadian Survey of Self-Management Strategies and Satisfaction with Ability to Control Pain: Comparison of Community Dwelling Adults with Neuropathic Pain versus Adults with Non-neuropathic Chronic Pain.

BACKGROUND: Individuals with chronic pain with neuropathic characteristics (CPNC) describe a different pain experience compared with those with chronic pain without neuropathic characteristics (CP). AIMS: The aim of this study was to describe and compare pain, self-management strategies, and satisfaction with ability to control pain between adults with CPNC versus CP. PARTICIPANTS: Seven hundred and ten community-dwelling adults with chronic pain participated in a cross-sectional survey. METHODS: CPNC was defined as a score ≥12 on the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale. Self-management and pain control was compared between participants with CPNC and CP using frequency, percent, relative risk (RR), odds ratios (ORs), and 95% confidence intervals (CIs). RESULTS: Participants with CPNC (188/710) reported lower socioeconomic status, poorer general health, and more intense, frequent, and widespread pain. They were more likely to use prescription medications to manage pain (adjusted OR = 2.25, CI = 1.47-3.42). They were more likely to use potentially negative strategies to ease the emotional burden of living with chronic pain, including substance use (adjusted OR = 1.58, CI = 1.06-2.35), denial (adjusted OR = 2.21, CI = 1.49-3.28), and behavioral disengagement (adjusted OR = 1.68, CI = 1.16-2.45), and they were more likely to be completely dissatisfied with their ability to control pain (RR = 1.77, CI = 1.21-2.58). CONCLUSIONS: Individuals with CPNC have distinct pain and self-management experiences compared with those with CP that may lead to negative coping strategies and dissatisfaction with ability to control pain. Therefore, self-management assessment and support should be tailored by pain condition.

[Practice-oriented pain therapy in dermatology : Concept with special emphasis on pain quality]. / Praxisorientierte Schmerztherapie in der Dermatologie : Konzept mit besonderer Berücksichtigung der Schmerzqualität.

In order to avoid chronification of pain, appropriate treatment has to be started as early as possible. Inpatient dermatology patients not only suffer from old age and associated multimorbidities but also from characteristic pain due to distinct dermatological diseases. In many cases clinicians have little experience with specific pain treatment but instead have many concerns about how to deal with analgesics. So far chronic pain has been treated according to the pain ladder of the World Health Organization (WHO), which prioritizes the intensity of pain. This article presents an easily implementable concept of pain therapy with special emphasis on the quality of pain. This provides information on whether it is neuropathic or nociceptive pain, which can ultimately be differentially treated. The primary aim is to provide treating dermatologists with a concept to assist in the initiation of an efficient and correct pain therapy. This brief introduction of an individualized pain treatment can reduce the risk of chronification of pain, which can severely impair the quality of life particularly in dermatology patients and also the frequent stigmatization due to the dermatosis.

Neuropathic pain and SCI: Identification and treatment strategies in the 21st century.

Pain is a common complication in patients following spinal cord injury (SCI), with studies citing up to 80% of patients reporting some form of pain. Neuropathic pain (NP) makes up a substantial percentage of all pain symptoms in patients with SCI and is often complex. Given the high prevalence of NP in patients with SCI, proper identification and treatment is imperative. Indeed, identification of pain subtypes is a vital step toward determining appropriate treatment. A variety of pharmacological and non-pharmacological treatments can be undertaken including antiepileptics, tricyclic antidepressants, opioids, transcranial direct current stimulation, and invasive surgical procedures. Despite all the available treatment options and advances in the field of SCI medicine, providing adequate treatment of NP after SCI continues to be challenging. It is therefore extremely important for clinicians to have a strong foundation in the identification of SCI NP, as well as an understanding of appropriate treatment options. Here, we highlight the definitions and classification tools available for NP identification, and discuss current treatment options. We hope that this will not only provide a better understanding of NP for physicians in various subspecialties, but that it will also help guide future research on this subject.

Evaluation of Pain Syndromes, Headache, and Temporomandibular Joint Disorders in Children.

After a thorough review of the history and presentation of a child's facial pain, a targeted head and neck examination is critical to the appropriate diagnosis of facial pain and temporomandibular joint disorders. It is critical to distinguish between the structural (trauma, degenerative disease, and tumor) and nonstructural (neurogenic, myogenic, and psychological) causes of pain, which will allow for incorporation of appropriate strategies of medical, psychological, dental, and surgical therapies.