Search

Abstract: The 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) aims at improving the lives of persons with the lived experience of chronic pain by providing clearly defined and clinically useful diagnoses that can reduce stigma, facilitate communication, and improve access to pain management, among others. The aim of this study was to assess the perspective of people with chronic pain on these diagnoses. An international web-based survey was distributed among persons with the lived experience of chronic pain. After having seen an information video, participants rated the diagnoses on 8 endorsement scales (eg, diagnostic fit, stigma) that ranged from -5 to +5 with 0 representing the neutral point of no expected change. Overall ratings and differences between participants with chronic primary pain (CPP) and chronic secondary pain (CSP) were analyzed. N = 690 participants were included in the data analysis. The ratings on all endorsement scales were significantly higher than the neutral point of 0. The highest ratings were obtained for "openness" (2.95 ± 1.93) and "overall opinion" (1.87 ± 1.98). Participants with CPP and CSP did not differ in their ratings; however, those with CSP indicated an improved diagnostic fit of the new diagnoses, whereas participants with CPP rated the diagnostic fit of the new diagnoses similar to the fit of their current diagnoses. These results show that persons with the lived experience of chronic pain accept and endorse the new diagnoses. This endorsement is an important indicator of the diagnoses' clinical utility and can contribute to implementation and advocacy., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause of functional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD both in prodromal phases and during the subsequent stages of the disease, negatively affecting patient's quality of life and function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. Targeting motor symptoms by dopamine replacement or with neuromodulatory approaches may only partially control PD-related pain. Pain in general has been classified in PwPD according to the motor signs, pain dimensions, or pain subtypes. Recently, a new classification framework focusing on chronic pain was introduced to group different types of PD pains according to mechanistic descriptors: nociceptive, neuropathic, or neither nociceptive nor neuropathic. This is also in line with the International Classification of Disease-11 , which acknowledges the possibility of chronic secondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinion article, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced when classifying it as a stepping stone to discuss an integrative view of the current classification approaches and how clinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeutic efforts are presented, as well as a potential framework to address them in a patient-oriented manner., (Copyright © 2023 International Association for the Study of Pain.)

Abstract: Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. Across 5 diagnostically determined subgroups, we found features which are common across different aetiologies, eg, gain of function in pressure pain threshold (PPT) when assessing responses from the lower abdomen or pelvis (referred pain site). However, disease-specific phenotypes were also identified, eg, greater mechanical allodynia in endometriosis, despite there being large heterogeneities within diagnostic groups. The most common QST sensory phenotype was mechanical hyperalgesia (>50% across all the groups). A "healthy' sensory phenotype was seen in <7% of CPP participants. Specific QST measures correlated with sensory symptoms assessed by the painDETECT questionnaire (pressure-evoked pain [painDETECT] and PPT [QST] [ r = 0.47, P < 0.001]; mechanical hyperalgesia (painDETECT) and mechanical pain sensitivity [MPS from QST] [ r = 0.38, P = 0.009]). The data suggest that participants with CPP are sensitive to both deep tissue and cutaneous inputs, suggesting that central mechanisms may be important in this cohort. We also see phenotypes such as thermal hyperalgesia, which may be the result of peripheral mechanisms, such as irritable nociceptors. This highlights the importance of stratifying patients into clinically meaningful phenotypes, which may have implications for the development of better therapeutic strategies for CPP., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Abstract: The decades since the inauguration of the International Association for the Study of Pain have witnessed major advances in scientific concepts (such as the biopsychosocial model and chronic primary pain as a disease in its own right) and in new technologies and approaches (from molecular biology to brain imaging) that have inspired innovations in pain research. These have guided progress in pain management and education about pain for healthcare professionals, the general public, and administrative agencies., (Copyright © 2023 International Association for the Study of Pain.)

Abstract: The International Classification of Diseases ( ICD ) is applied worldwide for public health data collection among other use cases. However, the current version of the ICD ( ICD-10 ), to which the reimbursement system is linked in many countries, does not represent chronic pain properly. This study aims to compare the ICD-10 with the ICD-11 in hospitalized patients in terms of specificity, clinical utility, and reimbursement for pain management. The medical records of hospitalized patients consulted for pain management at Siriraj Hospital, Thailand, were reviewed, and all pain-related diagnoses were coded into ICD-10 and ICD-11 . The data of 397 patients showed unspecified pain was coded 78% in the ICD-10 and only 0.5% in the ICD-11 version. The difference gap in the proportion of unspecified pain between the 2 versions is wider than in the outpatient setting. The 3 most common codes for ICD-10 were other chronic pain, low back pain, and pain in limb. The 3 most common codes for ICD-11 were chronic cancer pain, chronic peripheral neuropathic pain, and chronic secondary musculoskeletal pain. As in many other countries, no pain-related ICD-10 codes were coded for routine reimbursement. The simulated reimbursement fee remained the same when adding 397 pain-related codings, even if the cost of pain management, such as cost of labor, existed. Compared with the ICD-10 version, the ICD-11 is more specific and makes pain diagnoses more visible. Thus, shifting from ICD-10 to ICD-11 has the potential to improve both the quality of care and the reimbursement for pain management., (Copyright © 2023 International Association for the Study of Pain.)

Pain perception can be studied as an inferential process in which prior information influences the perception of nociceptive input. To date, there are no suitable psychophysical paradigms to measure this at an individual level. We developed a quantitative sensory testing paradigm allowing for quantification of the influence of prior expectations versus current nociceptive input during perception. Using a Pavlovian-learning task, we investigated the influence of prior expectations on the belief about the varying strength of association between a painful electrical cutaneous stimulus and a visual cue in healthy subjects (N = 70). The belief in cue-pain associations was examined with computational modelling using a Hierarchical Gaussian Filter (HGF). Prior weighting estimates in the HGF model were compared with the established measures of conditioned pain modulation (CPM) and temporal summation of pain (TSP) assessed by cuff algometry. Subsequent HGF-modelling and estimation of the influence of prior beliefs on perception showed that 70% of subjects had a higher reliance on nociceptive input during perception of acute pain stimuli, whereas 30% showed a stronger weighting of prior expectations over sensory evidence. There was no association between prior weighting estimates and CPM or TSP. The data demonstrates relevant individual differences in prior weighting and suggests an importance of top-down cognitive processes on pain perception. Our new psychophysical testing paradigm provides a method to identify individuals with traits suggesting greater reliance on prior expectations in pain perception, which may be a risk factor for developing chronic pain and may be differentially responsive to learning-based interventions., (© 2023. The Author(s).)

Abstract: An improved classification of chronic pain is included in the 11 th revision of the International Classification of Diseases and Related Health Problems . For all diagnoses of chronic pain, an optional dimensional code for the chronic pain severity will supplement the categorical diagnoses. Pain severity combines pain intensity, pain-related interference, and pain-related distress. Each component is rated by the patient on a numerical rating scale (NRS) from 0 to 10 and subsequently translated into severity stages ("mild," "moderate," and "severe"). This study aimed to evaluate this severity code by comparing the ratings with established psychometric measures of pain-related interference and distress. An online survey was posted to self-help groups for chronic pain, and 595 participants (88.7% women, 59.5 ± 13.5 years) rated each of the severity parameters (pain intensity, pain-related interference, and pain-related distress) on an NRS from 0 to 10 and completed the Pain Disability Index and the Pain Coping Questionnaire (FESV, 3 subscales). The participants reported a mean pain intensity of 6.4 ± 1.9, mean pain-related interference of 6.7 ± 2.1, and mean pain-related distress of 5.7 ± 2.5. The respective NRS ratings showed substantial correlations with the Pain Disability Index score ( r = 0.65) and the FESV subscales ( r = 0.65, r = 0.56, r = 0.37). The extension code for pain severity is a valid and efficient way of recording additional dimensional pain parameters, which can be used to monitor the course of chronic pain and its treatment. The specifier's efficiency makes it possible to use the code when a questionnaire would not be feasible due to time constraints, such as in primary care., (Copyright © 2022 International Association for the Study of Pain.)

Abstract: The transient receptor potential ion channel TRPM3 is highly prevalent on nociceptive dorsal root ganglion (DRG) neurons, but its functions in neuronal plasticity of chronic pain remain obscure. In an animal model of nonspecific low back pain (LBP), latent spinal sensitization known as nociceptive priming is induced by nerve growth factor (NGF) injection. Here, we address the TRPM3-associated molecular basis of NGF-induced latent spinal sensitization at presynaptic level by studying TRPM3-mediated calcium transients in DRG neurons. By investigating TRPM3-expressing HEK cells, we further show the dynamic mitochondrial activity downstream of TRPM3 activation. NGF enhances TRPM3 function, attenuates TRPM3 tachyphylaxis, and slows intracellular calcium clearance; TRPM3 activation triggers more mitochondrial calcium loading than depolarization does, causing a steady-state mitochondrial calcium elevation and a delayed recovery of cytosolic calcium; mitochondrial calcium buffering accounts for approximately 40% of calcium influx subsequent to TRPM3 activation. TRPM3 activation provokes an outbreak of pulsatile superoxide production (mitoflash) that comes in the form of a surge in frequency being tunable. We suggest that mitoflash pulsations downstream of TRPM3 activation might be an early signaling event initiating pain sensitization. Tuning of mitoflash activity would be a novel bottom-up therapeutic strategy for chronic pain conditions such as LBP and beyond., (Copyright © 2022 International Association for the Study of Pain.)

Abstract: For the first time, the upcoming International Classification of Diseases and Related Health Problems, Eleventh Revision (ICD-11) will include a comprehensive classification of chronic pain, which is based on the biopsychosocial definition of chronic pain. This presents a great opportunity for pain research and clinical practice. The new classification consists of 7 main diagnostic categories of chronic pain, which are further divided into increasingly specific levels of diagnoses. Each diagnosis is characterized by clearly defined operationalized criteria. Future users will need to familiarize themselves with the new system and its application. The aim of the present publication is to provide users of the ICD-11 chronic pain classification with answers to frequently asked questions regarding the ICD-11 as a whole, the ICD-11 chronic pain classification, and its application to common pain syndromes. The questions compiled in this study reached the International Association for the Study of Pain Task Force through different routes (eg, at conferences, by letter, or during field testing). Furthermore, the authors collected questions posted to the ICD-11 browser and contacted early users of the classification to enquire about their most frequent difficulties when applying the new diagnoses. The authors of the present publication prepared answers to these frequently asked questions. This publication intends to act as a guide for the future users of the new ICD-11 chronic pain classification, hence facilitating its implementation., (Copyright © 2022 International Association for the Study of Pain.)

Abstract: 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 © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Abstract: Chronic pain affects 1 in 5 persons and contributes substantially to the global burden of disease. The 11th Revision of the International Classification of Diseases (ICD-11) includes a comprehensive classification of chronic pain. The aim of this ecological implementation field study was to evaluate the classification's interrater reliability and clinical utility in countries with different income levels. The study was conducted in 4 pain clinics in Cuba, India, and New Zealand. Twenty-one clinicians used the ICD-11 to diagnose and code n = 353 patients with chronic pain. Of these, 111 were assessed by 2 clinicians, and Fleiss' kappa was calculated to establish interrater reliability for any diagnosis assigned to ≥15 patients. The clinicians rated the clinical utility of all diagnoses. The interrater reliability could be calculated for 11 diagnoses. It was substantial for 10 diagnoses and moderate for 1 (kappa: 0.596-0.783). The mean clinical utility of the ICD-11 chronic pain diagnoses was rated as 8.45 ± 1.69/10. Clinical utility was rated higher for ICD-11 than for the commonly used classification systems (P < 0.001, η2 = 0.25) and differed between all centers (P < 0.001, η2 = 0.60). The utility of the ICD-11 diagnoses was rated higher than the commonly used diagnoses in Dunedin and Havana, and no difference was found in Kolkata and Hyderabad. The study showed the high interrater reliability of the new chronic pain diagnoses. The perceived clinical utility of the diagnoses indicates their superiority or equality compared with the classification systems currently used in pain clinics. These results suggest the global applicability of the classification in specialized pain treatment settings., (Copyright © 2021 International Association for the Study of Pain.)

Abstract: Because chronic pain has been poorly represented in the International Statistical Classification of Diseases and Related Health Problems (ICD) despite its significant contribution to the burden of disease worldwide, the International Association for the Study of Pain (IASP) developed a classification of chronic pain that was included in the ICD-11 version as "MG30" and approved by the World Health Assembly in 2019. The objective of this field test was to determine how well the classification of chronic pain works in the context of the ICD-11. A web-based survey using the WHO-FiT platform recruited 177 healthcare professionals from all WHO regions. After a training on coding chronic pain hosted by the IASP Web site, participants evaluated 18 diagnostic codes (lines) of the 2017 frozen version of the ICD-11 and 12 vignettes (cases) describing chronic pain conditions. Correctness, ambiguity, and perceived difficulty of the coding were compared between the ICD-11 and the ICD-10 and the applicability of the morbidity rules for the ICD-11 verified. In the line coding, 43.0% of correct chronic pain diagnoses assigned with the ICD-10 contrasted with 63.2% with the ICD-11. Especially in cases in which the chronic pain is regarded as the symptom of an underlying disease, the ICD-11 (63.5%) commanded more correct diagnoses than the ICD-10 (26.8%). The case coding was on average 83.9% accurate, only in 1.6% of cases any difficulty was perceived. The morbidity rules were applied correctly in 74.1% of cases. From a coding perspective, the ICD-11 is superior to the ICD-10 in every respect, offering better accuracy, difficulty, and ambiguity in coding chronic pain conditions., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Abstract: Postoperative pain management is still insufficient, leading to major deficits, including patient suffering, impaired surgical recovery, long-term opioid intake, and postsurgical chronic pain. Yet, identifying the best treatment options refers to a heterogeneous outcome assessment in clinical trials, not always reflecting relevant pain-related aspects after surgery and therefore hamper evidence synthesis. Establishing a core outcome set for perioperative pain management of acute pain after surgery may overcome such limitations. An international, stepwise consensus process on outcome domains ("what to measure") for pain management after surgery, eg, after total knee arthroplasty, sternotomy, breast surgery, and surgery related to endometriosis, was performed. The process, guided by a steering committee, involved 9 international stakeholder groups and patient representatives. The face-to-face meeting was prepared by systematic literature searches identifying common outcome domains for each of the 4 surgical procedures and included breakout group sessions, world-café formats, plenary panel discussions, and final voting. The panel finally suggested an overall core outcome set for perioperative pain management with 5 core outcome domains: physical function (for a condition-specific measurement), pain intensity at rest, pain intensity during activity, adverse events, and self-efficacy. Innovative aspects of this work were inclusion of the psychological domain self-efficacy, as well as the specific assessment of pain intensity during activity and physical function recommended to be assessed in a condition-specific manner. The IMI-PROMPT core outcome set seeks to improve assessing efficacy and effectiveness of perioperative pain management in any clinical and observational studies as well as in clinical practice., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Abstract: The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses., (Copyright © 2021 International Association for the Study of Pain.)

Abstract: Pain is a frequent reason for patients to ask for medical services. However, systematic information about the extent and impact of pain, especially in developing countries, has not been available up to now. We evaluated whether the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD) can fill this gap by coding all electronic out-patient medical records of the pain clinic at Siriraj Hospital in Thailand in 2019 (8714 visits), using the ICD-10 and ICD-11 browsers referenced on the WHO websites. The 3 most frequent pain-related codes in ICD-10 were R52.2 "other chronic pain" (29%), M54.5 "low back pain" (18%), and M79.6 "pain in limb" (13%). In ICD-11, the 3 most frequent codes were MG30.31 "chronic secondary musculoskeletal pain associated with structural changes" (28%), MG30.51 "chronic peripheral neuropathic pain" (26%), and MG30.10 "chronic cancer pain" (23%). Thus, using the currently valid ICD-10 system, roughly one-third of patient encounters were coded as "other chronic pain," and the next 2 were specifying the pain region rather than any underlying cause. By contrast, ICD-11 coding of the same patients identified underlying causes (bones and joints, somatosensory nervous system, cancer, or surgery), which provide guidance towards differential patient management. In our pain clinic, most patients suffered from chronic cancer pain, chronic neuropathic pain, and chronic secondary musculoskeletal pain, which were poorly defined or nonexistent in the current ICD-10 coding system. Compared with the ICD-10, the ICD-11 provides more detailed diagnostic categories and is more informative for clinical use, research, and resource allocation for pain-related conditions., (Copyright © 2021 International Association for the Study of Pain.)

Background: The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients., Methods: At total of 240 neuropathic pain patients and 253 healthy volunteers were included. Patients were phenotypically characterized using standardized quantitative sensory testing (QST). Patients and controls were genotyped for HTR2A g.-1438G > A (rs6311) and c.102C > T (rs6313). Genotype-related differences in QST parameters were assessed considering QST profile clusters, principal somatosensory components and sex., Results: There was an equal distribution of rs6313 and linked rs6311 between patients and controls. However, the rs6313 variant was significantly associated with a principal component of pinprick hyperalgesia and dynamic mechanical allodynia, indicating enhanced CS in patients with sensory loss (-0.34 ± 0.15 vs. +0.31 ± 0.11 vs., p < .001). In this cluster, the variant allele was also associated with single QST parameters of pinprick hyperalgesia (MPT, +0.64 ± 0.18 vs. -0.34 ± 0.23 p = .002; MPS, +0.66 ± 0.17 vs. -0.09 ± 0.23, p = .009) and ongoing pain was increased by 30%., Conclusions: The specific association of the rs6313 variant with pinprick hyperalgesia and increased levels of ongoing pain suggests that the HTR2A receptor might be an important modulator in the development of CS in neuropathic pain., Significance: This article presents new insights into serotonin receptor 2A-mediating mechanisms of central sensitization in neuropathic pain patients. The rs6313 variant allele was associated with increased mechanical pinprick sensitivity and increased levels of ongoing pain supporting a contribution of central sensitization in the genesis of ongoing pain providing a possible route for mechanism-based therapies., (© 2020 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

The hippocampus is an important region for the interaction between depression and pain. Studies show that the P2X4 receptor plays key role in neuropathic pain. This work investigated the potential implication of the P2X4 receptor in the hippocampus in comorbidity of chronic pain and depression. The rat model induced by chronic constriction injury (CCI) plus unpredictable chronic mild stress (UCMS) was used in this study. Our data showed that CCI plus UCMS treatment resulted in abnormal changes in pain and depressive-like behaviors in the rat, accompanied by the upregulated expression of P2X4, NLRP3 (NOD-like receptor protein 3) inflammasome, and interleukin-1β and the activation of p38 MAPK in the hippocampus. The P2X4 antagonist 5-BDBD reversed these abnormal changes in the hippocampus, relieved hippocampal neuronal damage, and alleviated the abnormal pain and depressive-like behaviors in the CCI plus UCMS treated rats. These findings suggest that the P2X4 receptor in the hippocampus may mediate and significantly contribute to the pathological processes of comorbid pain and depression.

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.

Quantitative sensory testing (QST) is a formal variant of a time-honoured clinical examination technique in neurology, the sensory examination. Prototypical QST profiles have been found in human surrogate models of peripheral sensitization, central sensitization, and deafferentation. Probabilistic sorting of individual patients to any combination of these profiles has been developed, and there is emerging evidence for the predictive value of such sensory profiles for treatment efficacy. This way, QST aids in diagnostics of individual patients and may help guide their care in the future. Deficits in "dynamic" QST have been proposed as predictors of chronic pain (impaired descending inhibition and delayed recovery from central sensitization). Several psychological factors had previously been found to be predictors of pain chronicity (catastrophizing, self-efficacy, and neuroticism). The relative importance of psychological vs sensory testing predictors has not been evaluated. It is likely that both will have differential roles in clinical practice.

Background: Chronic pain is often accompanied by comorbidities like anxiety and depression. The temporal correlations, as well as the underlying mechanisms of these reciprocal correlations, are unclear. Moreover, preclinical studies examining emotional behaviour are very controversial, and a chronological analysis of anxiety-like behaviour in mouse pain models considering both genders has not been performed so far., Methods: We used several behavioural tests to assess and validate anxiety-like behaviour in complete Freund's adjuvant (CFA) and spared nerve injury (SNI) pain models in C57BL/6 mice. Among these were the elevated plus maze test, open field test, hole-board test and light-dark test. Additionally, we included a late stage analysis of depression-like behaviour using the forced swim test. All tests were applied once for each cohort of mice. Importantly, we used C57BL/6N mice of both genders; we investigated the effect of social isolation, the impact of pain induction to either the right or left hind limb and also investigated C57BL/6J mice., Results: The validity of test conditions was confirmed using the anxiogenic drugs Yohimbine and Pentylenetetrazol. Anxiety-like behaviour was analysed throughout the time period when mice exhibited hypersensitivity to mechanical stimuli. We did not observe any consistent alteration in anxiety-like behaviour at any of the investigated time points between 1 and 14 days following CFA-induced inflammation or 3 and 84 days following SNI surgery using different behavioural tests., Conclusions: Inflammatory and neuropathic pain conditions do not primarily evoke anxiety- and depression-like behavioural alterations within the herein investigated time period., Significance: Anxiety-like behaviour is not primarily altered following CFA and SNI in C57BL6 mice, irrespective of the gender, mouse sub-strain, housing conditions or affected body side within the herein investigated time period., (© 2018 European Pain Federation - EFIC®.)

Chronic musculoskeletal pain is defined as chronic pain arising from musculoskeletal structures such as bones or joints. Although comprising the most prevalent set of chronic pain conditions, it was not represented appropriately in the 10th edition of the International Classification of Diseases (ICD-10), which was organized mainly according to anatomical sites, was strongly focused on musculoskeletal disease or local damage, and did not consider the underlying mechanisms of pain. The new ICD-11 classification introduces the concept of chronic primary and secondary musculoskeletal pain, and integrates the biomedical axis with the psychological and social axes that comprise the complex experience of chronic musculoskeletal pain. Chronic primary musculoskeletal pain is a condition in its own right, not better accounted for by a specific classified disease. Chronic secondary musculoskeletal pain is a symptom that arises from an underlying disease classified elsewhere. Such secondary musculoskeletal pain originates in persistent nociception in musculoskeletal structures from local or systemic etiologies, or it may be related to deep somatic lesions. It can be caused by inflammation, by structural changes, or by biomechanical consequences of diseases of the nervous system. It is intended that this new classification will facilitate access to patient-centered multimodal pain management and promote research through more accurate epidemiological analyses.

This article describes chronic secondary headache and chronic orofacial pain (OFP) disorders with respect to the new International Classification of Diseases (ICD-11). The section refers extensively to the International Classification of Headache Disorders (ICHD-3) of the International Headache Society that is implemented in the chapter on Neurology in ICD-11. The ICHD-3 differentiates between primary (idiopathic) headache disorders, secondary (symptomatic) headache disorders, and OFP disorders including cranial neuralgias. Chronic headache or OFP is defined as headache or OFP that occurs on at least 50% of the days during at least 3 months and lasting at least 2 hours per day. Only chronic secondary headache and chronic secondary OFP disorders are included here; chronic primary headache or OFP disorders are listed under chronic primary pain syndromes that have been described in a companion publication. The subdivisions of chronic secondary OFP of ICHD-3 are complemented by the Diagnostic Criteria for Temporomandibular Disorders and contributions from the International Association for the Study of Pain Special Interest Group on Orofacial and Head Pain and include chronic dental pain. The ICD-11 codes described here are intended to be used in combination with codes for the underlying diseases, to identify patients who require specialized pain management. In addition, these codes shall enhance visibility of these disorders in morbidity statistics and motivate research into their mechanisms.

This article describes a proposal for the new diagnosis of chronic primary pain (CPP) in ICD-11. Chronic primary pain is chosen when pain has persisted for more than 3 months and is associated with significant emotional distress and/or functional disability, and the pain is not better accounted for by another condition. As with all pain, the article assumes a biopsychosocial framework for understanding CPP, which means all subtypes of the diagnosis are considered to be multifactorial in nature, with biological, psychological, and social factors contributing to each. Unlike the perspectives found in DSM-5 and ICD-10, the diagnosis of CPP is considered to be appropriate independently of identified biological or psychological contributors, unless another diagnosis would better account for the presenting symptoms. Such other diagnoses are called "chronic secondary pain" where pain may at least initially be conceived as a symptom secondary to an underlying disease. The goal here is to create a classification that is useful in both primary care and specialized pain management settings for the development of individualized management plans, and to assist both clinicians and researchers by providing a more accurate description of each diagnostic category.

Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperation with the WHO, an IASP Working Group has developed a classification system that is applicable in a wide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in our proposal, we call this subgroup "chronic primary pain." In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as "chronic secondary pain" where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right.

Physical, mental, and social well-being are part of the concept of health according to the World Health Organization, in addition to the absence of disease and infirmity. Therefore, for a full description of a person's health status, the International Classification of Functioning, Disability and Health (ICF) was launched in 2001 to complement the existing International Classification of Diseases (ICD). The 11th version of the ICD (ICD-11) is based on so-called content models, which have 13 main parameters. One of them is functioning properties (FPs) that, according to the WHO, consist of the activities and participation components of the ICF. Recently, chronic pain codes were added to the 11th edition of the ICD, and hence, a specific set of FPs for chronic pain is required as a link to the ICF. In addition, pain is one of the 7 dimensions of the generic set of the ICF, which applies to any person. Thus, assessment and management of pain are also important for the implementation of the ICF in general. This article describes the current consensus proposal by the International Association for the Study of Pain (IASP) and the International Society of Physical and Rehabilitation Medicine (ISPRM) for a specific set of FPs of chronic pain, which will have to be empirically validated in a next step. The combined use of ICD-11 and ICF is expected to improve research reports on chronic pain by a more precise and adequate coding, as well as patient management through better diagnostic classification.

The International Classification of Diseases, 11th Revision (ICD-11), proposes, for the first time, a coding system for chronic pain. This system contains 1 code for "chronic primary pain," where chronic pain is the disease, and 6 codes for chronic secondary pain syndromes, where pain developed in the context of another disease. This provides the opportunity for routine, standardised coding of chronic pain throughout all health care systems. In primary care, this will confer many important, novel advantages over current or absent coding systems. Chronic pain will be recognized as a centrally important condition in primary care. The capacity to measure incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address chronic pain in primary care. Finally, opportunities to match evidence-based treatment pathways to distinct chronic pain subtypes will be enhanced.

Chronic visceral pain is a frequent and disabling condition. Despite high prevalence and impact, chronic visceral pain is not represented in ICD-10 in a systematic manner. Chronic secondary visceral pain is chronic pain secondary to an underlying condition originating from internal organs of the head or neck region or of the thoracic, abdominal, or pelvic regions. It can be caused by persistent inflammation, by vascular mechanisms or by mechanical factors. The pain intensity is not necessarily fully correlated with the disease process, and the chronic visceral pain may persist beyond successful treatment of the underlying cause. This article describes how a new classification of chronic secondary visceral pain is intended to facilitate the diagnostic process and to enable the collection of accurate epidemiological data. Furthermore, it is hoped that the new classification will improve the tailoring of patient-centered pain treatment of chronic secondary visceral pain and stimulate research. Chronic secondary visceral pain should be distinguished from chronic primary visceral pain states that are considered diseases in their own right.

Background: A task force of the International Association for the Study of Pain (IASP) has developed a classification of chronic pain for the ICD-11 consisting of seven major categories. The objective was to test whether the proposed categories were exhaustive and mutually exclusive. In addition, the perceived utility of the diagnoses and the raters' subjective diagnostic certainty were to be assessed., Methods: Five independent pain centers in three continents coded 507 consecutive patients. The raters received the definitions for the main diagnostic categories of the proposed classification and were asked to allocate diagnostic categories to each patient. In addition, they were asked to indicate how useful they judged the diagnosis to be from 0 (not at all) to 3 (completely) and how confident they were in their category allocation., Results: The two largest groups of patients were coded as either chronic primary pain or chronic secondary musculoskeletal pain. Of the 507 patients coded, 3.0% had chronic pain not fitting any of the proposed categories (97% exhaustiveness), 20.1% received more than one diagnosis. After adjusting for double coding due to technical reasons, 2.0% of cases remained (98% uniqueness). The mean perceived utility was 1.9 ± 1.0, the mean diagnostic confidence was 2.0 ± 1.0., Conclusions: The categories proved exhaustive with few cases being classified as unspecified chronic pain, and they showed themselves to be mutually exclusive. The categories were regarded as useful with particularly high ratings for the newly introduced categories (chronic cancer-related pain among others). The confidence in allocating the diagnoses was good although no training regarding the ICD-11 categories had been possible at this stage of the development.

Chronic pain is the greatest source of disability globally and claims related to chronic pain feature in many insurance and medico-legal cases. Brain imaging (for example, functional MRI, PET, EEG and magnetoencephalography) is widely considered to have potential for diagnosis, prognostication, and prediction of treatment outcome in patients with chronic pain. In this Consensus Statement, a presidential task force of the International Association for the Study of Pain examines the capabilities of brain imaging in the diagnosis of chronic pain, and the ethical and legal implications of its use in this way. The task force emphasizes that the use of brain imaging in this context is in a discovery phase, but has the potential to increase our understanding of the neural underpinnings of chronic pain, inform the development of therapeutic agents, and predict treatment outcomes for use in personalized pain management. The task force proposes standards of evidence that must be satisfied before any brain imaging measure can be considered suitable for clinical or legal purposes. The admissibility of such evidence in legal cases also strongly depends on laws that vary between jurisdictions. For these reasons, the task force concludes that the use of brain imaging findings to support or dispute a claim of chronic pain - effectively as a pain lie detector - is not warranted, but that imaging should be used to further our understanding of the mechanisms underlying pain.

Findings considering conditioned pain modulation (CPM) in chronic back pain (CBP) are contradictory. This might be because many patients with CBP report pain in further areas of the body, and altered CPM might influence spatial extent of pain rather than CBP per se. Therefore, we compared CPM in patients with CBP with different pain extent. Patients with fibromyalgia syndrome (FMS), for whom CPM impairment is reported most consistently, were measured for comparison. Based on clinical evaluation and pain drawings, patients were categorized into chronic local back pain (CLP; n = 53), chronic widespread back pain (CWP; n = 32), and FMS (n = 92). Conditioned pain modulation was measured by the difference in pressure pain threshold (test stimuli) at the lower back before and after tonic heat pain (conditioning stimulus). We also measured psychosocial variables. Pressure pain threshold was significantly increased in CLP patients after tonic heat pain (P < 0.001) indicating induction of CPM. Conditioned pain modulation in CLP was significantly higher than that in CWP and FMS (P < 0.001), but CPM in CWP and FMS did not differ. Interestingly, a higher number of painful areas (0-10) were associated with lower CPM (r = 0.346, P = 0.001) in CBP but not in FMS (r = -0.013, P = 0.903). Anxiety and depression were more pronounced in FMS than in CLP or CWP (P values <0.01). Our findings suggest that CPM dysfunction is associated with CWP and not with FMS as suggested previously. FMS seems to differ from CWP without FMS by higher psychosocial burden. Moreover, patients with CBP should be stratified into CLP and CWP, and centrally acting treatments targeting endogenous pain inhibition seem to be more indicated the higher the pain extent.

Childhood maltreatment (CM) has been associated with an increased risk of nonspecific chronic low back pain (nsCLBP). However, the mechanisms underlying this association are unclear. Therefore, this study considered whether distinct types of CM are accompanied by specific alterations in somatosensory function. A total of 176 subjects with nsCLBP and 27 pain-free controls (PCs) were included. The Childhood Trauma Questionnaire (CTQ) was used to categorize patients into 2 groups (abused/neglected vs nonabused/nonneglected) for 5 types of CM (emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect). The standardized quantitative sensory testing protocol of the "German Research Network on Neuropathic Pain" was performed to obtain comprehensive profiles on somatosensory function, including detection and pain thresholds, pain sensitivity, and assessments of temporal summation (wind-up). Between 17.7% and 51.4% of subjects with nsCLBP reported CM, depending on the type of CM. Childhood Trauma Questionnaire subscores for emotional and sexual abuse were significantly higher in subjects with nsCLBP than in PCs. Compared with PCs, subjects with CM showed reduced pressure pain thresholds (PPTs), irrespective of the type of CM. Regarding distinct types of CM, subjects with nsCLBP with emotional abuse reported significantly higher wind-up than those without, and sexual abuse was accompanied by enhanced touch sensitivity. Our findings suggest that CM is nonspecifically associated with a decreased PPT in nsCLBP. Emotional abuse apparently leads to enhanced spinal pain summation, and sexual abuse leads to enhanced touch sensitivity. These results emphasize the importance of emotional abuse in nsCLBP and suggest that CM can induce long-term changes in adult somatosensory function.

Objectives: Whether chronic localized pain (CLP) and chronic widespread pain (CWP) have different mechanisms or to what extent they overlap in their pathophysiology is controversial. The study compared quantitative sensory testing profiles of nonspecific chronic back pain patients with CLP (n=48) and CWP (n=29) with and fibromyalgia syndrome (FMS) patients (n=90) and pain-free controls (n = 40)., Materials and Methods: The quantitative sensory testing protocol of the "German-Research-Network-on-Neuropathic-Pain" was used to measure evoked pain on the painful area in the lower back and the pain-free hand (thermal and mechanical detection and pain thresholds, vibration threshold, pain sensitivity to sharp and blunt mechanical stimuli). Ongoing pain and psychometrics were captured with pain drawings and questionnaires., Results: CLP patients did not differ from pain-free controls, except for lower pressure pain threshold (PPT) on the back. CWP and FMS patients showed lower heat pain threshold and higher wind-up ratio on the back and lower heat pain threshold and cold pain threshold on the hand. FMS showed lower PPT on back and hand, and higher comorbidity of anxiety and depression and more functional impairment than all other groups., Discussion: Even after long duration CLP presents with a local hypersensitivity for PPT, suggesting a somatotopically specific sensitization of nociceptive processing. However, CWP patients show widespread ongoing pain and hyperalgesia for different stimuli that is generalized in space, suggesting the involvement of descending control systems, as also suggested for FMS patients. Because mechanisms in nonspecific chronic back pain with CLP and CWP differ, these patients should be distinguished in future research and allocated to different treatments.

Psychological trauma is associated with an increased risk for chronification of nonspecific chronic back pain (nsCLBP) independent of posttraumatic stress disorder (PTSD). However, the mechanisms underlying the role of psychological trauma in nsCLBP are less clear than in PTSD. Therefore, this study considered whether psychological trauma exposure (TE) is accompanied by specific alterations in pain perception. The study included 56 participants with nsCLBP and TE (nsCLBP-TE), 93 participants with nsCLBP without TE (nsCLBP-W-TE), and 31 pain-free controls. All participants underwent a thorough clinical evaluation. The standardized quantitative sensory testing protocol of the "German Research Network on Neuropathic Pain" was used to obtain comprehensive profiles on somatosensory functions in painful (back) and non-painful areas (hand). The protocol consisted of thermal and mechanical detection as well as pain thresholds, vibration thresholds, and pain sensitivity to sharp and blunt mechanical stimuli. Psychological trauma was validated by structured clinical interview. Trauma-associated symptom severity, anxiety, and depressive symptomatology were assessed by self-report questionnaires. Differences in somatosensory function were seen only for pressure pain thresholds. Compared with controls, nsCLBP-TE revealed hyperalgesia generalized in space with lower thresholds in painful and non-painful areas, whereas nsCLBP-W-TE demonstrated localized alterations with decreased thresholds only in the pain-affected area of the back (P ≤ 0.006). Our findings suggest an augmented central pain processing in nsCLBP-TE (alterations in painful and non-painful areas), whereas nsCLBP-W-TE show only local changes (alterations only in the painful area) suggesting regional sensitization processes. This finding might explain why TE without PTSD is associated with an increased prevalence of chronic pain.

Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

Copyright of Pain Research / Ból is the property of Index Copernicus International and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development. [ABSTRACT FROM AUTHOR]