Nociceptive Pain Component Research Articles

Unraveling the physiological and psychosocial signatures of pain by machine learning.

Pain is a complex subjective experience, strongly impacting health and quality of life. Despite many attempts to find effective solutions, present treatments are generic, often unsuccessful, and present significant side effects. Designing individualized therapies requires understanding of multidimensional pain experience, considering physical and emotional aspects. Current clinical pain assessments, relying on subjective one-dimensional numeric self-reports, fail to capture this complexity. To this aim, we exploited machine learning to disentangle physiological and psychosocial components shaping the pain experience. Clinical, psychosocial, and physiological data were collected from 118 chronic pain and healthy participants undergoing 40 pain trials (4,697 trials). To understand the objective response to nociception, we classified pain from the physiological signals (accuracy >0.87), extracting the most important biomarkers. Then, using multilevel mixed-effects models, we predicted the reported pain, quantifying the mismatch between subjective level and measured physiological response. From these models, we introduced two metrics: TIP (subjective index of pain) and Φ (physiological index). These represent possible added value in the clinical process, capturing psychosocial and physiological pain dimensions, respectively. Patients with high TIP are characterized by frequent sick leave from work and increased clinical depression and anxiety, factors associated with long-term disability and poor recovery, and are indicated for alternative treatments, such as psychological ones. By contrast, patients with high Φ show strong nociceptive pain components and could benefit more from pharmacotherapy. TIP and Φ, explaining the multidimensionality of pain, might provide a new tool potentially leading to targeted treatments, thereby reducing the costs of inefficient generic therapies. RESC-PainSense, SNSF-MOVE-IT197271.

Application of painDETECT in Pediatric Chronic Pain: How Well Does It Identify Neuropathic Pain and Its Characteristics?

Pediatric neuropathic pain is difficult to diagnose, and when undetected is associated with functional disability, mental health concerns, and decreased quality of life. PainDETECT is a screening tool developed to differentiate neuropathic from nociceptive pain components, thus guiding treatment decision-making and improving outcomes. Therefore, the purpose of this study was to evaluate how well painDETECT can identify neuropathic pain and its characteristics in a pediatric population. Adolescents (10-24yo) were recruited from two major children's hospitals. Participants completed painDETECT and two quantitative sensory tasks (QST) that assess mechanical allodynia (brush) and pressure pain (algometer) as part of an ongoing study. Pain diagnoses were collected via parent report and participant medical chart, when unclear. Descriptive statistics and ANOVAs were used to characterize participants and assess painDETECT in relation to diagnosis and QST measures. Participants with chronic pain diagnoses (N=110, Mage=15.05±2.4, Nfemale=88) and peers without pain (N=55, Mage=15.84±3.9, Nfemale=39) were included. As expected, painDETECT scores for participants with pain (M=11.51±6.59) were higher than peers without pain (M=1.42±2.15). Among those diagnosed with neuropathic pain, painDETECT identified 88.5% as having neuropathic pain. Among those diagnosed with abdominal, endometriosis, and fibromyalgia, 75% were identified as having nociceptive pain and 0% as having neuropathic pain. For those diagnosed with musculoskeletal and pain amplification, 61% were identified as having nociceptive pain and 19.6% as having neuropathic pain. Individuals in the neuropathic pain category had significantly higher mechanical allodynia (p=.021) and lower pressure pain thresholds (p=.059). PainDETECT differentiated participants with pain from their peers without pain and demonstrated accuracy in identifying participants as having nociceptive vs. neuropathic pain, consistent with their existing pain diagnosis. Moreover, QST results were consistent with a positive neuropathic screening. Taken together, results support the use of painDETECT as a pediatric neuropathic pain screening tool. Grant support from 5R01HD83270.

Pain syndrome in oncology. Possibilities of dexketoprofen administration

Pain is an important problem in oncology patients. Depending on its intensity, for pain treatment, analgesics of different pharmacological classes are used. According to WHO recommendations, for nociceptive pain treatment in oncology patients, non-steroidal antiinflammatory drugs (NSAIDs), mild and potent opioids are the essential medications. If in pain formation along with the nociceptive pain component, a neuropathic one is present, antiepilepsy drugs, tricyclic antidepressants, local anesthetics are added. Apart from these medicines, adjuvants are used. These agents potentiate the analgesic endpoint of NSAIDs and opioids, correct their adverse effects. Often, intensive pain development is driven by bone metastases, which form in oncologic processes of different primary localization. Herewith, patients could suffer from constant as well as from paroxysmal, “breakthrough” pain. The efficacy of NSAIDs in oncology patients is due not only to analgesic effect but also to their action on inflammatory processes in areas of tumor formation and growth as well as in metastatic foci. Dexketoprofen trometamol is an effective and safe NSAID, a water-soluble salt of a dexketoprofen dextrorotatory stereoisomer. The preparation has a good lipid and water solubility. Thus, dexketoprofen trometamol can rapidly absorb, create therapeutic concentrations in blood serum, and penetrate through brain-blood barrier. It produces a significant and fast analgesic action in different diseases, which is related both to central analgesic mechanisms and to anti-inflammatory effect in peripheral tissues. Dexketoprofen trometamol efficacy is proven in bone pain related to oncological disease. The availability of intravenous solution and the prompt action at oral administration allow using the medicine for “breakthrough” pain. The medication significantly potentiates the action of mild and potent opioids at combined therapy, which allows to use opioid analgesics in lower doses.

Characterizing Abdominal Pain in Patients With Gastroparesis Into Neuropathic and Nociceptive Components.

The cause of abdominal pain (AP) in gastroparesis (Gp) is often not known; hence, its treatment can be challenging. Preoccupation with or increased attention (hypervigilance) to pain is associated with perceived pain severity and psychosocial disability. The aims of this study were to (1) characterize AP in Gp patients into neuropathic and nociceptive pain components; (2) assess these patients for hypervigilance to pain. Gp patients with AP as an important symptom, seen from June 2017 to November 2017 were given validated questionnaires to characterize their AP. Carnett's sign (worsened AP/tenderness on head/shoulder lift and/or leg lift) was assessed on examination. Of 32 patients (87% females), 20 had idiopathic Gp, and 9 had diabetic Gp. AP severity using Patient Assessment of Gastrointestinal Symptoms averaged 4.3±0.2 (standard error of mean) for upper AP and 2.3±0.3 for lower AP. AP was typically located in epigastrium (53.1%), and described as sharp (75%). Eleven patients (35.5%) met criteria for neuropathic pain on Neuropathic Pain Questionnaire. Twenty patients (62.5%) had positive Carnett's sign suggesting somatic pain. Fifteen patients (48.4%) were hypervigilant to pain on Pain Vigilance and Awareness Questionnaire. Of Gp patients with AP, over one third have a neuropathic component to their pain whereas nearly two thirds have characteristics of somatic pain. Almost half of the Gp patients with AP are hypervigilant to pain. Determining the underlying cause of AP and hypervigilance to pain in Gp patients may assist in devising appropriate treatment strategies.

Clinical characteristics of pain in patients with pituitary adenomas.

Clinical presentation of pituitary adenomas frequently involves pain, particularly headache, due to structural and functional properties of the tumour. Our aim was to investigate the clinical characteristics of pain in a large cohort of patients with pituitary disease. In a cross-sectional study, we assessed 278 patients with pituitary disease (n=81 acromegaly; n=45 Cushing's disease; n=92 prolactinoma; n=60 non-functioning pituitary adenoma). Pain was studied using validated questionnaires to screen for nociceptive vs neuropathic pain components (painDETECT), determine pain severity, quality, duration and location (German pain questionnaire) and to assess the impact of pain on disability (migraine disability assessment, MIDAS) and quality of life (QoL). We recorded a high prevalence of bodily pain (n=180, 65%) and headache (n=178, 64%); adrenocorticotropic adenomas were most frequently associated with pain (n=34, 76%). Headache was equally frequent in patients with macro- and microadenomas (68 vs 60%; P=0.266). According to painDETECT, the majority of the patients had a nociceptive pain component (n=193, 80%). Despite high prevalence of headache, 72% reported little or no headache-related disability (MIDAS). Modifiable factors including tumour size, genetic predisposition, previous surgery, irradiation or medical therapy did not have significant impact neither on neuropathic pain components (painDETECT) nor on headache-related disability (MIDAS). Neuropathic pain and pain-related disability correlated significantly with depression and impaired QoL. Pain appears to be a frequent problem in pituitary disease. The data suggest that pain should be integrated in the diagnostic and therapeutic work-up of patients with pituitary disease in order to treat them appropriately and improve their QoL.

Assessment of Neuropathic Pain in Patients with Cancer: The Interobserver Reliability. An Observational Study in Daily Practice

Background: Neuropathic pain (NeP) is a burdensome problem in all stages of cancer. Although clinical judgment is accepted as a surrogate for an objective gold standard in diagnosing NeP, no publications were found about its reliability. Objectives: Therefore, levels of agreement on the clinical examination of NeP were estimated by calculating kappa-value (Κ) and percentage of pair wise agreement (PA) to determine the interobserver reliability of diagnosing NeP. Setting: The outpatient clinic of medical oncology of the Radboud University Nijmegen Medical Centre. Methods: Patients with cancer with potential NeP complaints were recruited from the outpatient clinic of medical oncology. Physicians were recruited from the department of pain and palliative medicine. Physicians and patients were recruited for participation in an observational study in daily practice. Each patient (N = 34) was examined by 2 specialists via independent clinical assessment. All consultations were video recorded. After each assessment, physicians were asked to indicate the most adequate characterization of the pain: pure NeP, pure nociceptive pain (NoP), mixed pain (MiP), or no pain (NP). Results: Kappa (Κ) for the diagnosis of the most adequate pain characterization was 0.50, PA 64.7%. For diagnosing pure NeP k was 0.78 (PA 91.2%), for the NeP component (NeP + MiP) and NoP component (NoP + MiP), it was respectively 0.52 (PA 76.5%) and 0.61 (PA 82.4%). For the diagnosis on the basis of the grading system between physicians, Κ was 0.34 (PA 52.9%). The intrarater reliability for the diagnosis of an NeP component on the basis of clinical assessment and the NeP component on the basis of the grading system, for pain specialists Κ was 0.69 (PA 85.3%) and for palliative care specialists Κ was 0.61 (PA 79.4%). Limitations: The values of Κ and the PA for the existence of an NeP component are not satisfying and the clinical agreement between physicians around findings from physical examination should encourage a better standardization of the clinical assessment and classification of pain in patients with cancer in respect with the identification of NeP. Conclusions: A substantial level of agreement was found for the diagnosis of pure NeP and a moderate level of agreement for the diagnosis of the NeP component was found, both with a PA ≥ 70%. There was only a fair agreement between the physicians regarding the grading system. However, there was a substantial level of (interrater) agreement for the diagnosis of an NeP component and the outcome of the grading system. The findings in this study also suggest that a better standardization of the clinical assessment and classification of pain in patients with cancer with respect to the identification of neuropathic pain is necessary. Key words: Neuropathic pain, diagnosis, interobserver reliability, agreement, cancer observational study, pain, clinical assessment, diagnostic test