Neuropathic Pain Component Research Articles

Effects of Intense Pulsed Light on Presumed Neuropathic Pain Associated with Meibomian Gland Dysfunction: A Before-After Study.

Purpose: Meibomian gland dysfunction (MGD) may cause chronic ocular surface pain (COSP) with a neuropathic component that can significantly impact quality of life and be poorly responsive to conventional treatments of MGD. Intense pulsed light (IPL) is an emerging treatment already acknowledged as improving refractory MGD, potentially modulating inflammatory mediators on the ocular surface. This study aimed to assess the impact of IPL on COSP associated with unresponsive MGD. Methods: A monocentric prospective study has been conducted from 2021 to 2023 on patients presenting with moderate MGD and COSP non-responsive to conventional treatments of MGD. Neuropathic pain components were suspected when severe discomfort (OSDI score above 33/100) was observed despite moderate objective signs. Three sessions of IPL were performed at a two-week interval. The primary outcome was change in OSDI at day 60. Secondary outcomes included OSDI modification at D120, DEQ-5, and Pentascore results at D60/D120, together with changes in clinical [Schirmer I, Fluorescein Break-up time (BUT), fluorescein staining, and MGD classification] and paraclinical tests [noninvasive BUT, tear meniscus height (TMH), and meibography]. Results: A significant improvement of COSP (p < 0.05 for changes in OSDI and Pentascore results) was observed 2 and 4 months after the last IPL session, together with an improvement in tear film stability, corneal epitheliopathy, meibomian gland obstruction, and TMH. Conclusion: The results of this study suggest the beneficial effect of IPL on neuropathic component of COSP associated with MGD. The underlying mechanisms involved in that improvement, presumably related to downgrading of inflammatory effectors, remain however to be explored.

Post-Torakotomi Ağrı Sendromu: İnsidans, Nöropatik Bileşen ve Risk Faktörleri

Objective: Pain that recurs or persists at least two months after thoracotomy is defined as post-thoracotomy pain syndrome (PTPS), and neuropathic pain (NP) is expected to develop in approximately half of these patients. This study aimed to examine the frequency of PTPS, the neuropathic component of pain, and the effecting risk factors in patients who underwent thoracotomy. Methods: 862 patients who underwent thoracotomy were monitored between January 2010 and May 2013 at Gazi University Faculty of Medicine Hospital. The study continued with 277 patients who could be contacted by phone at least three months after the operation. In these patients, the presence of pain was questioned, if present, the severity of pain, NP and affecting risk factors were investigated. The pain severity and NP component were evaluated using the Numeric Rating Scale (NRS) and Douleur Neuropathique 4 (DN4) questionnaires, respectively. Results: Severe PTPS frequency after thoracotomy was found to be 19.1 % and NP was present in 53% of patients with NRS 3-10. As the severity of pain increased, the frequency of NP and analgesic drug consumption increased (p&lt;0.05). As risk factors gender, age, operation duration and epidural analgesia application did not significantly affect the frequency and severity of PTPS and NP. As the time after the operation increased; PTSP frequency, neuropathic pain frequency and pain intensity were decreased (p&lt;0.05). Conclusion: Severe PTPS is detected in approximately one in five patients who undergone thoracotomy and half of them had NP. The neuropathic component of pain increases as pain intensity increases and decreases as time passes after surgery. The development of PTPS and NP should be reduced by providing effective analgesia. Keywords: Thoracotomy, chronic pain, post-thoracotomy pain syndrome, neuropathic pain

A Meta-analysis Exploring the Efficacy of Neuropathic Pain Medication for Low Back Pain or Spine-Related Leg Pain: Is Efficacy Dependent on the Presence of Neuropathic Pain?

Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed todetermine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy. EMBASE, MEDLINE,Cochrane Central,CINAHL[EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry weresearched from inception to 14 May, 2024.Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework. Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] - 9.30 [95% confidence interval [CI] - 13.71, - 4.88], I2 = 87%) and medium term (MD - 5.49 [95% CI - 7.24, - 3.74], I2 = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD - 16.65 [95% CI - 35.95, 2.65], I2 = 84%; probable; MD - 10.45 [95% CI - 14.79, - 6.12], I2 = 20%) than studies including people with possible (MD - 5.50 [95% CI - 20.52, 9.52], I2 = 78%), unlikely (MD - 6.67 [95% CI - 10.58, 2.76], I2 = 0%), or unclear neuropathic pain (MD - 8.93 [95% CI - 20.57, 2.71], I2 = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD - 3.35 [95% CI - 9.00, 2.29], I2 = 93%) and medium term (MD - 4.06 [95% CI - 5.63, - 2.48], I2 = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD - 9.25 [95% CI - 12.59, - 5.90], I2 = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD -1.57 [95% CI - 8.96, 5.82] I2 = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes. Most studies using neuropathic pain medication for low back pain or spine-related leg pain fail to adequately consider the presence of neuropathic pain. Meta-analyses suggest neuropathic pain medication may be most effective in people with low back pain or spine-related leg pain with a definite/probable neuropathic pain component. However, the low to very low certainty of evidence and poor identification of neuropathic pain in most studies prevent firm recommendations.

Activation of TGR5 in the injured nerve site according to a prevention protocol mitigates partial sciatic nerve ligation-induced neuropathic pain by alleviating neuroinflammation.

Neuropathic pain is a pervasive medical challenge currently lacking effective treatment options. Molecular changes at the site of peripheral nerve injury contribute to both peripheral and central sensitization, critical components of neuropathic pain. This study explores the role of the G-protein-coupled bile acid receptor (GPBAR1 or TGR5) in the peripheral mechanisms underlying neuropathic pain induced by partial sciatic nerve ligation in male mice. TGR5 was upregulated in the injured nerve site and predominantly colocalized with macrophages. Perisciatic nerve administration of the TGR5 agonist, INT-777 according to a prevention protocol (50 μg/μL daily from postoperative day [POD] 0 to POD6) provided sustained relief from mechanical allodynia and spontaneous pain, whereas the TGR5 antagonist, SBI-115 worsened neuropathic pain. Transcriptome sequencing linked the pain relief induced by TGR5 activation to reduced neuroinflammation, which was further evidenced by a decrease in myeloid cells and pro-inflammatory mediators (eg, CCL3, CXCL9, interleukin [IL]-6, and tumor necrosis factor [TNF] α) and an increase in CD86-CD206+ anti-inflammatory macrophages at POD7. Besides, myeloid-cell-specific TGR5 knockdown in the injured nerve site exacerbated both neuropathic pain and neuroinflammation, which was substantiated by bulk RNA-sequencing and upregulated expression levels of inflammatory mediators (including CCL3, CCL2, IL-6, TNF α, and IL-1β) and the increased number of monocytes/macrophages at POD7. Furthermore, the activation of microglia in the spinal cord on POD7 and POD14 was altered when TGR5 in the sciatic nerve was manipulated. Collectively, TGR5 activation in the injured nerve site mitigates neuropathic pain by reducing neuroinflammation, while TGR5 knockdown in myeloid cells worsens pain by enhancing neuroinflammation.

Postoperative pain after parotid surgery-comparison between superficial/total parotidectomy and extracapsular dissection: a prospective observational study.

To evaluate postoperative pain and discomfort after parotid surgery with regard to different surgical approaches. This clinical study was carried out at a single tertiary referral center (2021-2022) and included 2 groups of adult patients (mean age 56.6 ± 12.7 vs. 53.4 ± 14.1years) following elective parotid surgery due to a parotid tumor of any entity.The first group (SP/TP group) consisted of 31 patients after superficial parotidectomy (SP) or total parotidectomy (TP) (n = 31). The second group (ECD group) included all patients who had undergone extracapsular dissection (ECD) (n = 51). Primary endpoints comprised pain on ambulation as well as maximum and minimum pain (NRS 0-10) on the first three postoperative days (PODs). A neuropathic pain component (evaluated on POD 1 and 3), the analgesic score (collected from the patient file on POD 1-3), treatment-related side-effects/pain-associated impairments, and patient satisfaction (all measured on the 1st POD) were defined as secondary endpoints. Patients were surveyed using the standardized and validated "Quality Improvement in Postoperative Pain Treatment" (QUIPS) questionnaire and the painDETECT® questionnaire. Comparisons were performed using independent t tests, Wilcoxon tests, and χ2 tests, and the respective effect sizes were calculated. Looking at the first postoperative day, patients of both groups (SP/TP vs. ECD) reported comparable pain on ambulation (2.8 ± 2.0 vs. 2.6 ± 1.8; p = 0.628, r = 0.063), maximum (3.5 ± 2.2 vs. 3.5 ± 2.3; p = 0.992, r = 0.002) and minimum pain (1.1 ± 1.04 vs. 1.0 ± 1.2; p = 0.206, r = 0.157). Furthermore, there were no significant differences in pain-related restrictions or pain medication requirement. The patients in both groups were equally satisfied with their pain therapy (p = 0.282, R = 0.135). The sum score of the painDETECT® questionnaire delivered clearly negative (< 12) results on average (POD1: 6.81; POD3: 6.59); no significant difference between the groups was found (p = 0.991, R2 < .001). Neither surgical technique on the parotid gland was significantly superior to the other in terms of postoperative pain perception. Overall, postoperative pain can be classified as mild to moderate following parotid surgery. A neuropathic pain component could be excluded for the acute postoperative phase. The study was registered in the German Registry for Clinical Studies (DRKS) (application No.: DRKS00016520).

On the problem of neuropathic pain component diagnosis in patients with cancer pain syndrome

Neuropathic pain component occurs in every second patient with pain syndrome caused by a malignant tumor. Detection of the neuropathic component of pain syndrome is crucial for selection of effective analgesia.The review presents an application algorithm for an updated system of neuropathic pain component assessment in oncological patients.

People with osteoarthritis have a higher component of neuropathic pain as compared to those with rheumatoid arthritis: A cross-sectional study.

Neuropathic pain may be present in a proportion of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Its presence may lead to the requirement of altered management approaches in these conditions. This study investigated the prevalence of neuropathic pain in OA as compared to that in RA. Patients with OA and RA were included cross-sectionally if they had no other known neuropathic disorder. The PainDETECT questionnaire was used to assess neuropathic pain. WOMAC and CDAI scores were used to assess disease severity in OA and RA respectively. 69 patients with OA with a mean WOMAC score of 53.30 ± 16.39 and 98 patients with RA with a mean CDAI of 25.48 ± 16.99 were compared. The median PainDETECT score for OA was 13 (0-30) and RA was 5 (0-37) [p<0.001]. 15 patients with OA and six patients with RA were highly likely to have neuropathic pain, while 15 patients with OA and 30 patients with RA were classified as possibly having neuropathic pain. Thus, the proportion of patients free from neuropathic pain was higher in the RA group (63.3%) than in the OA group (39.1%) [p = 0.003]. Both the prevalence and the severity of neuropathic pain were significantly higher in OA than in RA. These findings suggest that neuropathic pain is an important factor in OA, as in RA, and must be considered in management as well as in future research in both these conditions.

Determining the frequency of occurrence of the neuropathic component of chronic cancer pain

The original study was conducted to study the prevalence and incidence of the neuropathic component of chronic pain in patients with malignant neoplasms. The cohort study sample was formed in the Regional Oncology Dispensary of Karaganda. The study included 374 cancer patients. Neuropathic chronic pain of varying intensity and localization was diagnosed in 106 patients. The sample patients were divided into the main and control groups using the envelope method. Each group was analyzed in detail, the main clinical characteristics of each patient were described. Gender, age, localization and prevalence of the primary focus of malignant neoplasm, and the type of antitumor treatment were analyzed.The original study found that the neuropathic component of chronic pain is more common in women over 50 years of age. In the vast majority of cases, such patients are diagnosed with stage III breast cancer who have undergone complex or combined treatment. Given the identified cohort of patients who develop chronic neuropathic pain, it is possible to begin preventive measures earlier. These measures will reduce the burden of developing a difficult-to-treat type of chronic pain among cancer patients.

Neuropathic component of chronic musculoskeletal pain in patients with post-COVID-19: A cross-sectional study.

This study aimed to evaluate the neuropathic component of chronic musculoskeletal pain in post-coronavirus disease 2019 (COVID-19) and examine the relationship between neuropathic pain and clinical and demographic characteristics. This cross-sectional study included 163 adult patients (85 females, 78 males; mean age: 41.7±4.3 years; range, 22 to 50 years) with post-COVID-19 musculoskeletal pain between February 1, 2021, and April 30, 2021. Demographic and clinical characteristics, including age, sex, affected site, duration, and severity of post-COVID-19 musculoskeletal pain using the Visual Analog Scale (VAS), as well as a neuropathic component of pain using the Leeds assessment of neuropathic symptoms and signs (LANSS), were collected. The most common post-COVID-19 symptoms, presence of hospitalization, and length of hospital stay during active COVID-19 infection were recorded from the patient records. The mean duration and severity of pain were 7.85±1.53 months and 5.09±1.95, respectively. Half of the patients were hospitalized, and the mean length of hospital stay was 12.15±18.06 days. The most common pain sites were upper and lower back pain, followed by leg and arm pain. A total of 92 (56.4%) patients had previously received pharmacological or nonpharmacological treatment for post-COVID-19 musculoskeletal pain. Based on the LANSS (scores >12), 31 (19%) patients had neuropathic pain. There was a significant correlation between the presence of neuropathic pain and pulmonary involvement/symptoms. The presence and length of hospital stay were correlated with LANNS scores (p<0.05). The frequency, LANSS scores, and VAS-pain scores of the patients with and without neuropathic pain were similar between male and female patients (p>0.05). The neuropathic component of chronic musculoskeletal pain may be common, as one-fifth of our patients had neuropathic pain as assessed by the LANNS. Therefore, the awareness of post-COVID-19 chronic neuropathic musculoskeletal pain should be increased. We believe that focusing on the identification of pain phenotypes would provide adequate and tailored chronic neuropathic musculoskeletal pain management in the post-COVID-19 period.

Conservative combination therapy of sciatica due to lumbar disc herniation with mechanical physiotherapy (McKenzie), gabapentin, and transforaminal epidural injections

Treatment of sciatica due to lumbar disc herniation can be surgical or conservative. Conservative management has been described to be effective in 90% of patients; however, in most studies no consistent treatment concept was used. In the present study, we evaluated the effect of acombined nonsurgical management (McKenzie physiotherapy, gabapentin, and periradicular injections) in 40patients during a10-day inpatient treatment. In addition to the neuro-orthopedic examination, pain severity at rest and after walking were assessed. The Oswestry pain disability scale, the pain severity scale, and the painDETECT scale were examined to assess neuropathic pain components. The duration of incapacity for work and the requirement of alater surgery were recorded. Examinations were performed on the day of admission, on days3, 6, 10, and84, 3months after discharge. During conservative treatment, acontinuous reduction of pain and an improvement of the straight leg raise test as well as finger-to-floor distance could be documented. As the three treatment options were introduced with atime delay, it could be demonstrated that all significantly contributed to the improvement. All treatments were tolerated without side-effects and persistent improvement after 12weeks. On admission, 32% of patients revealed aneuropathic pain component which decreased to 7% at the follow-up. A total of 28patients showed impaired muscle strength on admission, which decreased to 7patients on follow-up. Electromyography revealed pathological results in 70% of patients examined. Asignificant improvement of quality of life (Oswestry Disability Index [ODI]) could be observed and the patients returned to work after 5.8weeks. Only 3/40patients required surgical management due to persistent pain. The combined nonsurgical operative treatment program is effective and well tolerated.

Pain Detect as A Tool for The Screening of Neuropathic Pain in Patients with Diabetes Mellitus

Background: Diabetic neuropathy (DN) is a prevalent long-term complication of diabetes mellitus (DM), affecting more than 50% of patients. In addition, several studies also showed that distal symmetric polyneuropathy (DSPN) accounts for 75% of all DN cases. To facilitate the treatment of DN, painDETECT questionnaire, a self-reported tool with 85% sensitivity and 80% specificity, has been recommended for detecting neuropathic component in pain. Objective: This study aimed to promptly diagnose DN using painDETECT questionnaire in DM patients. Methods: The study procedures were carried out using a descriptive, cross-sectional design with 67 DM patients from Cibabat Regional Hospital Department of Internal Medicine outpatient clinic through consecutive sampling in October–November 2022. Primary data were obtained using the adapted and validated Indonesian painDETECT questionnaire. Results: Among the 67 patients, 32.9% experienced neuropathic pain with a score of 19–38, indicating the involvement of &gt;90% of neuropathic pain components. Sensory deficits, such as numbness, burning sensation, pins-and-needles, and allodynia, were observed in 86.3%, 90.1%, and 72.7% of patients with neuropathic pain, respectively. In addition, a total of 59.7% of participants (n=40) reported the presence of mild pain (NRS 3). Conclusion: Based on the results, the majority of patients had complaints of neuropathic or mild pain (40 subjects; 59.7%). Among the 22 patients experiencing neuropathic pain, 54.5% reported mild intensity.

DN4 questionnaire as a useful tool for evaluating the pharmacotherapeutic response to opioid pharmacotherapy in malignant neuropathy.

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Discovery of a CCR2-targeting pepducin therapy for chronic pain

Targeting the CCL2/CCR2 chemokine axis has been shown to be effective at relieving pain in rodent models of inflammatory and neuropathic pain, therefore representing a promising avenue for the development of non-opioid analgesics. However, clinical trials targeting this receptor for inflammatory conditions and painful neuropathies have failed to meet expectations and have all been discontinued due to lack of efficacy. To overcome the poor selectivity of CCR2 chemokine receptor antagonists, we generated and characterized the function of intracellular cell-penetrating allosteric modulators targeting CCR2, namely pepducins. In vivo, chronic intrathecal administration of the CCR2-selective pepducin PP101 was effective in alleviating neuropathic and bone cancer pain. In the setting of bone metastases, we found that T cells infiltrate dorsal root ganglia (DRG) and induce long-lasting pain hypersensitivity. By acting on CCR2-expressing DRG neurons, PP101 attenuated the altered phenotype of sensory neurons as well as the neuroinflammatory milieu of DRGs, and reduced bone cancer pain by blocking CD4+ and CD8+ T cell infiltration. Notably, PP101 demonstrated its efficacy in targeting the neuropathic component of bone cancer pain, as evidenced by its anti-nociceptive effects in a model of chronic constriction injury of the sciatic nerve. Importantly, PP101-induced reduction of CCR2 signaling in DRGs did not result in deleterious tumor progression or adverse behavioral effects. Thus, targeting neuroimmune crosstalk through allosteric inhibition of CCR2 could represent an effective and safe avenue for the management of chronic pain.

Assessing the effects of distinct biologic therapies on rheumatoid arthritis pain by nociceptive, neuropathic and nociplastic pain components: a randomised feasibility study

BackgroundPain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies.MethodsThe BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134.ResultsDuring the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19.ConclusionsThis first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation.Trial registrationNCT04255134, Registered on Feb 5, 2020.

Current understanding of nociplastic pain.

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.

Prevalence and Management of Chronic Pain, Including Neuropathic Pain, in Dialysis Patients with End-Stage Renal Disease.

BACKGROUND Chronic kidney disease (CKD) is a growing global health concern. Chronic pain, as a common symptom of CKD, particularly among patients with end-stage renal disease (ESRD), is influenced by complications, dialysis procedures, and comorbidities. We aimed to evaluate chronic pain and probable neuropathic pain in 96 dialysis patients with ESRD using the Douleur Neuropathique 4 (DN4) questionnaire. MATERIAL AND METHODS A total of 96 patients from a single dialysis center were enrolled for the purpose of this study. ESRD was caused by diseases causing kidney damage, such as diabetes. The average duration of maintenance dialysis was 4.6±5.67 years. Comorbidities, functional and mental assessment, and pharmacological treatment data were collected using a questionnaire. The satisfaction with life scale was also used. Chronic pain was defined as lasting more than 3 months. The DN4 was used to determine the neuropathic component of pain. RESULTS Chronic pain was observed in 63.5% of the study participants, with 47.5% of them reporting the presence of neuropathic pain accompanied by a neuropathic component. Significantly more patients with chronic pain reported mood disorders and reduced life satisfaction, but there was no difference in their activities of daily living-assessed functional status or duration of dialysis. Patients experiencing chronic pain received non-steroidal anti-inflammatory drugs, paracetamol, and opioids. CONCLUSIONS Chronic pain, especially with a neuropathic component, is highly prevalent in patients with CKD, and its treatment remains ineffective. Undiagnosed components of pain can contribute to underdiagnosis and inadequate therapy. Further studies and staff education are needed to address this important issue.

Can we achieve pain stratification in musculoskeletal conditions? Implications for clinical practice.

In the last few years there has been an increased appreciation that pain perception in rheumatic and musculoskeletal diseases (RMDs) has several mechanisms which include nociceptive, inflammatory, nociplastic and neuropathic components. Studies in specific patient groups have also demonstrated that the pain experienced by people with specific diagnoses can present with distinctive components over time. For example, the pain observed in rheumatoid arthritis has been widely accepted to be caused by the activation of nociceptors, potentiated by the release of inflammatory mediators, including prostaglandins, leukotrienes and cytokine networks in the joint environment. However, people with RA may also experience nociplastic and neuropathic pain components, particularly when treatments with disease modifying anti-rheumatic drugs (DMARDs) have been implemented and are insufficient to control pain symptoms. In other RMDs, the concept of pain sensitisation or nociplastic pain in driving ongoing pain symptoms e.g. osteoarthritis and fibromyalgia, is becoming increasingly recognised. In this review, we explore the hypothesis that pain has distinct modalities based on clinical, pathophysiological, imaging and genetic factors. The concept of pain stratification in RMD is explored and implications for future management are also discussed.

Chronic postsurgical pain: A European survey.

Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. To find predictive factors for CPSP in an international survey. Observational study. Multicentre European prospective observational trial. Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA). Standardised questionnaires were completed by the patients at 1, 3, and 7 days, and at 1, 3, and 6 months after surgery, with follow-up via E-mail, telephone, or interview. The primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery. A total of 3297 patients were included from 18 hospitals across Europe and 2494 patients were followed-up for 6 months. The mean incidence of CPSP at 6 months was 10.5%, with variations depending on the type of surgery: sternotomy 6.9%, breast surgery 7.4%, TKA 12.9%, endometriosis 16.2%. At 6 months, neuropathic characteristics were frequent for all types of surgery: sternotomy 33.3%, breast surgery 67.6%, TKA 42.4%, endometriosis 41.4%. One-third of patients experienced CPSP at both 3 and 6 months. Pre-operative pain was frequent for TKA (leg pain) and endometriosis (abdomen) and its frequency and intensity were reduced after surgery. Severe CPSP and a neuropathic pain component decreased psychological and functional wellbeing as well as quality of life. No overarching CPSP risk factors were identified. Unfortunately, our findings do not offer a new CPSP predictive score. However, we present reliable new data on the incidence, characteristics, and consequences of CPSP from a large European survey. Interesting new data on the time course of CPSP, its neuropathic pain component, and CPSP after endometriosis surgery generate new hypotheses but need to be confirmed by further research. clinicaltrials.gov ID: NCT03834922.

Association of nociplastic and neuropathic pain components with the presence of residual symptoms in patients with axial spondyloarthritis receiving biological disease-modifying antirheumatic drugs

ObjectiveTo evaluate the association of nociplastic (NoP) and neuropathic pain (NP) components with residual symptoms in patients with radiographic axial spondyloarthritis (r-axSpA) receiving biological disease-modifying antirheumatic drugs (bDMARDs).Methods78 patients with...

Chronic neuropathic pain components in whiplash-associated disorders correlate with metabolite concentrations in the anterior cingulate and dorsolateral prefrontal cortex: a consensus-driven MRS re-examination.

Whiplash injury (WHI) is characterised by a forced neck flexion/extension, which frequently occurs after motor vehicle collisions. Previous studies characterising differences in brain metabolite concentrations and correlations with neuropathic pain (NP) components with chronic whiplash-associated disorders (WAD) have been demonstrated in affective pain-processing areas such as the anterior cingulate cortex (ACC). However, the detection of a difference in metabolite concentrations within these cortical areas with chronic WAD pain has been elusive. In this study, single-voxel magnetic resonance spectroscopy (MRS), following the latest MRSinMRS consensus group guidelines, was performed in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and occipital cortex (OCC) to quantify differences in metabolite concentrations in individuals with chronic WAD with or without neuropathic pain (NP) components. Healthy individuals (n = 29) and participants with chronic WAD (n = 29) were screened with the Douleur Neuropathique 4 Questionnaire (DN4) and divided into groups without (WAD-noNP, n = 15) or with NP components (WAD-NP, n = 14). Metabolites were quantified with LCModel following a single session in a 3 T MRI scanner within the ACC, DLPFC, and OCC. Participants with WAD-NP presented moderate pain intensity and interference compared with the WAD-noNP group. Single-voxel MRS analysis demonstrated a higher glutamate concentration in the ACC and lower total choline (tCho) in the DLPFC in the WAD-NP versus WAD-noNP group, with no intergroup metabolite difference detected in the OCC. Best fit and stepwise multiple regression revealed that the normalised ACC glutamate/total creatine (tCr) (p = 0.01), DLPFC n-acetyl-aspartate (NAA)/tCr (p = 0.001), and DLPFC tCho/tCr levels (p = 0.02) predicted NP components in the WAD-NP group (ACC r 2 = 0.26, α = 0.81; DLPFC r 2 = 0.62, α = 0.98). The normalised Glu/tCr concentration was higher in the healthy than the WAD-noNP group within the ACC (p < 0.05), but not in the DLPFC or OCC. Neither sex nor age affected key normalised metabolite concentrations related to WAD-NP components when compared to the WAD-noNP group. This study demonstrates that elevated glutamate concentrations within the ACC are related to chronic WAD-NP components, while higher NAA and lower tCho metabolite levels suggest a role for increased neuronal-glial signalling and cell membrane dysfunction in individuals with chronic WAD-NP components.