Neuropathic pain, mood, and stress-related disorders: A literature review of comorbidity and co-pathogenesis.

Neuropathic pain can be caused by multiple factors, and its prevalence can reach 10% of the global population. It is becoming increasingly evident that limited or short-lasting response to treatments for neuropathic pain is associated with psychological factors, which include psychiatric comorbidities known to affect quality of life. It is estimated that 60% of patients with neuropathic pain also experience depression, anxiety, and stress symptoms. Altered mood, including stress, can be a consequence of several painful conditions but can also favor pain chronicization when preexisting. Despite the apparent tight connection between clinical pain and mood/stress disorders, the exact physiological mechanisms remain unclear. This review aims to provide an overview of state-of-the-art research on the mechanisms of pain related to the pathophysiology of depression, anxiety, and stress disorders.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

Neuropathic pain in patients with osteoarthritis of the hip before and after total hip arthroplasty.

OBJECTIVES: The pain associated with osteoarthritis (OA) was thought to be nociceptive; however, neuropathic pain is also observed. We investigated the relationship between hip OA and neuropathic pain using the PainDETECT questionnaire (PDQ). METHODS: A total of 159 hips of 146 consecutive patients who underwent total hip arthroplasty (THA) with a diagnosis of OA were enrolled in this study. The prevalence of each pain phenotype was evaluated preoperatively and at 6 months postoperatively using the PDQ. Patient characteristics and numerical rating scale (NRS) scores were compared between a group with possible neuropathic pain (NP group) and a group with nociceptive pain (non-NP group). RESULTS: Before THA, neuropathic, unclear, and nociceptive pain was observed in 18, 36, and 105 hips, respectively. The prevalence in the NP group was 54 hips, accounting for approximately one-third of all hips, which decreased significantly to seven hips after THA. A significantly higher NRS score was observed in the NP group, both before and after THA. CONCLUSION: Approximately one-third of the patients with hip OA had neuropathic pain. Therefore, neuropathic pain should be considered when treating patients with hip OA.

Neuropathic pain and mood disorders in earthquake survivors with peripheral nerve injuries.

Background and purpose:

        Natural disasters, such as earthquakes, frequently result in mood disorders among affected individuals. It is established that neuropathic pain arising from traumatic neuropathies is also linked to mood disorders. This study investigates the influence of neuropathic pain on the development of mood disorders in earthquake survivors with peripheral nerve injuries, following the earthquake centered in Kahramanmaras on February 6, 2023. Additionally, we aim to assess the electro­physiological aspects of neuropathic injuries in these survivors.

The study comprised 46 earth-quake survivors with electrophysiologically confirmed peripheral nerve injuries, with 39 trauma-free survivors serving as the control group. Neuropathic pain, anxiety and depression were assessed using the Douleur Neuropathique 4 (DN4) questionnaire and the Hospital Anxiety and Depression Scale (HADS).

Our findings revealed that the ulnar and peroneal nerves were the most commonly injured structures. Among the survivors with peripheral nerve injury, 31 out of 46 (67%) were found to experience neuropathic pain. Furthermore, plexopathy and multiple extremity injuries were associated with more severe neuropathic pain. However, there was no significant difference in anxiety and depression scores between the two groups and neuropathic pain was found to have no independent effect.

The study indicates that the intensity of neuropathic pain varies based on the localization and distribution of peripheral nerve injuries. However, the presence of peripheral nerve damage or neuropathic pain was not directly associated with HADS scores, suggesting that mood disorders following disasters may have multifactorial causes beyond physical trauma.

Anti-Plexin-D1 Seropositive Small Fiber Neuropathy: Clinical Phenotype, Demographics, and Literature Review.

OBJECTIVES: Small fiber neuropathy (SFN) is a subtype of painful neuropathies defined by dysfunction of the Aδ and unmyelinated C fibers. It presents with both neuropathic pain and dysautonomia symptoms, posing a significant diagnostic and therapeutic challenge. To address this challenge, research has been conducted to identify autoantibodies and define their association with phenotypes. METHODS: Eleven cases of anti-plexin-D1 seropositive SFN were reviewed, along with relevant literature, in attempt to better define anti-plexin-D1 SFN demographics, symptoms, associated medical conditions, and therapeutics. RESULTS: Anti-plexin-D1 SFN typically presents in female patients, with neuropathic pain, normal skin biopsy findings, and normal nerve conduction studies. Anti-plexin-D1 shows an association with concurrent chronic pain, with almost half of the patients undergoing an interventional procedure. CONCLUSIONS: Anti-plexin-D1 represents a unique subgroup of SFN, defined by distinct demographics, phenotype, biopsy findings, and therapeutic management.

Incidence and risk factors for developing chemotherapy-induced neuropathic pain in 500 cancer patients: A file-based observational study.

OBJECTIVE: To define the incidence and risk factors for developing chemotherapy-induced neuropathic pain (CINP). METHODS: Retrospective, file-based analysis on cancer patients who received any type of conventional chemotherapy and for whom neurological evaluation was asked to reveal the extent of chemotherapy-induced peripheral neurotoxicity (CIPN) with or without CINP. CINP was assessed by means of the PI-NRS and Douleur Neuropathique-4 questionnaire. The total neuropathy score-clinical version graded the severity of CIPN. RESULTS: The medical files of 500 chemotherapy-treated cancer patients were reviewed. Any grade chronic CIPN was disclosed in 343 (68.6%) patients and CINP in 127 (37%) of them, corresponding to an overall percentage of 25.4% among all 500 included patients. The logistic regression analysis identified as independent predictors for CINP development the presence of uncomplicated diabetes (OR: 2.17; p = .039) and grade 2-3 chronic CIPN (OR: 1.61; p < .001) as also the administration of combined paclitaxel plus cisplatin (reference variable), compared to oxaliplatin (OR: 0.18; p = .001) and taxanes (OR: 0.16; p < .001). The increased severity of acute OXAIPN was associated with CINP (OR: 4.51; p < .001). OXA-treated patients with persistent CINP presented a worst likelihood to improve after chemotherapy discontinuation, than patients receiving combined paclitaxel plus cisplatin (OR: 50; p < .001). CONCLUSION: The incidence of CINP in our cohort was comparable to previous reports, with severities fluctuating upwards during chemotherapy and declined post-chemotherapy. Uncomplicated diabetes, the combined paclitaxel plus cisplatin treatment and the increased severity of acute oxaliplatin neurotoxicity mostly increase the risk for developing CINP. OXA-treated patients present less possibilities to recover from CINP after chemotherapy discontinuation, than other chemotherapies.

In subjects with chronic low back pain, does neuropathia exclusively correlated to neuronal compression? A correlation study of PainDETECT questionnaire and corresponding MRI and X-ray findings.

INTRODUCTION: Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP), nociceptive (NoP), and ambiguous pain. This study aimed to investigate the relationship between pain classification and lumbar intervertebral degenerative parameters obtained from imaging. METHODS: A cohort study was conducted involving 279 patients, aged 18 years and above, who completed PainDETECT questionnaires and underwent lumbar MRI and/or X-ray scans. RESULTS: The study included 102 patients with NoP, 78 with ambiguous pain, and 99 with NeP. The NeP group had lower mean age (58.21 vs. 53.63, p < 0.05) and higher mean numerical rating scale score (7.9 vs. 5.9, p < 0.001) compared to the NoP group. A negative correlation was found between PainDETECT scores and pelvic incidence (τ = - 0.177, p = 0.043). The NeP group exhibited significantly higher severity of foraminal stenosis (U = 18.962, p = 0.002), spinal stenosis (U = 14.481, p = 0.005), and Pfirrmann grade (U = 14.221, p = 0.028) compared to the NoP group. A higher proportion of NeP patients had intervertebral disk bulge (96% vs. 78% vs. 78%, p = 0.002) and high-intensity zones (51% vs. 41% vs. 19%, p < 0.001) compared to those with NoP and ambiguous pain. CONCLUSION: NeP, as determined by the PainDETECT questionnaire, is associated with more severe neural compression, increased presence of discogenic disease and inflammatory disk severity, and decreased pelvic incidence. This pioneering study establishes a connection between pathological findings and pain categorization, providing clinicians with valuable guidance for formulating tailored management plans and reducing the need for unnecessary pharmacotherapy, imaging, and non-targeted surgical interventions.

Risk factors of neuropathic pain in multiple sclerosis: a retrospective case-cohort study.

Background: Pain is a common symptom in multiple sclerosis (MS), especially neuropathic pain, which has a significant impact on patients' mental and physical health and quality of life. However, risk factors that related to neuropathic pain, still remain unclear. Objective: The study aimed to explore the risk factors of neuropathic pain among MS patients. Materials and methods: This retrospective study examined the consecutive patients diagnosed with MS in the Department of Neurology of Guangdong Provincial Hospital of Chinese Medicine between August 2011 and October 2022. Neuropathic pain was defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". Demographic and clinical features were obtained from the electronic system of the hospital. Results: Our cohort revealed that the prevalence of patients with neuropathic pain in MS was 34.1%. The results indicated that the longer the spinal lesions, the greater the neuropathic pain risks (2-4: OR, 13.3(2.1-82), >5: OR, 15.2(2.7-86.8), p for tread: 0.037). Meanwhile, multivariate regression analysis showed that cervical and thoracic lesions (OR 4.276, 95% CI 1.366-13.382, P = 0.013), upper thoracic lesions (T1-T6) (OR 3.047, 95% CI 1.018-9.124, P = 0.046) were positively correlated with neuropathic pain, while basal ganglia lesions (OR 0.188, 95% CI 0.044-0.809, P = 0.025) were negatively correlated with neuropathic pain among MS patients. Conclusion: Extended spinal lesions (≥3 spinal lesions), cervical and thoracic lesions, upper thoracic lesions were independent risk factors of neuropathic pain among MS patients. Furthermore, our study found that the longer the spinal lesions, the greater the neuropathic pain risks.

Prevalence and clinical profiles of anti-myelin-associated glycoprotein neuropathy in Japan: A nationwide survey study of 133 patients.

BACKGROUND AND PURPOSE: The aim of this study was to determine the prevalence of anti-myelin-associated glycoprotein (MAG) neuropathy and the current status of such patients in Japan. METHODS: We conducted a nationwide survey in 2021 using established epidemiological methods. Questionnaires were sent to all neurology and pediatric neurology departments throughout Japan to identify patients with anti-MAG neuropathy. An initial questionnaire was used to determine the number of patients, with a second one used to collect detailed clinical information. RESULTS: The estimated number of patients with anti-MAG neuropathy was 353, with a prevalence of 0.28 per 100,000 and an incidence of 0.05 per 100,000. The detailed clinical profiles of 133 patients were available. The median (range) age of onset was 67 (30-87) years, with a prominent peak in the age range 66-70 years, and the male-to-female ratio was 3.6. Most patients had distal sensory-predominant polyneuropathy, and neuropathic pain (50%), or sensory ataxia (42%), while 18% had Waldenström's macroglobulinemia or multiple myeloma. Intravenous immunoglobulin was the most frequently used treatment (65%), but the response rate was <50%, whereas rituximab was given in 32% of patients, and 64% of these showed improvement. At the last visit, 27% of patients could not walk independently. CONCLUSIONS: This study on anti-MAG neuropathy provides updated insights into the epidemiology of this disease, clinical profiles, and treatment approaches in Japan. Rituximab therapy, used for only one-third of the patients, demonstrated efficacy. During the final visit, a quarter of the patients were unable to walk independently. Further studies are warranted to determine the optimal management of this rare and intractable disorder.

Chronic postsurgical pain: A European survey.

BACKGROUND: Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. OBJECTIVE: To find predictive factors for CPSP in an international survey. DESIGN: Observational study. SETTING: Multicentre European prospective observational trial. PATIENTS: Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA). METHOD: 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. MAIN OUTCOME MEASURE: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03834922.

Frequency of idiopathic intracranial hypertension with ultrasound in patients with fibromyalgia: Relation with function, central sensitization, and neuropathic pain.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of idiopathic intracranial hypertension (IIH) in fibromyalgia (FMS) patients by utilizing ultrasound to measure the optic nerve sheath diameter (ONSD), a marker of elevated intracranial pressure and also to investigate the relationship with function, fatigue, quality of life (QOL), central sensitization (CS) and neuropathic pain. METHODS: The study encompassed 80 female FMS patients and 75 healthy controls. Ultrasound was employed to measure the average ONSD in both groups. Conditions potentially elevating intracranial pressure were ruled out following neurological assessments. Pain (via visual analog scale, VAS), function (revised Fibromyalgia Impact Questionnaire, r-FIQ), QOL (Short Form-36, SF-36), fatigue (fatigue severity scale, FACIT), CS (Central Sensitization Scale), and neuropathic pain (Douleur Neuropathique-4) were evaluated. RESULTS: The average ONSD was significantly higher in the patient group than the control group. Patients with ONSD >5.5 mm consistent with IIH were categorized as Group 1 (n = 54, 67.5%), while those with a diameter of 5.5 mm and below-formed Group 2. VAS pain (p = .033) and FIQ-R scores (p = .033) were significantly higher in Group 1 than Group 2. Headache was found more common in Group 1. CONCLUSION: This study unveils a substantial occurrence (67.5%) of IIH in FMS patients, suggesting shared pathophysiological mechanisms contributing to symptoms like fatigue, headache, and cognitive dysfunction. Additionally, these findings implicate heightened functional impairment, CS, headache, and fatigue in FMS patients with IIH.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study.

BACKGROUND: Endometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. OBJECTIVE: To characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. METHODS: We retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). RESULTS: Using a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. CONCLUSION: When controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

Prognosis of Patients With Neuropathic Low Back-Related Leg Pain: An Exploratory Study Using Prospective Data From UK Primary Care.

This prospective cohort study investigates the prognosis of patients with neuropathic low back-related leg pain consulting in UK primary care. Data from 511 patients were collected using standardised baseline clinical examinations (including magnetic resonance imaging scan findings), self-report questionnaires at baseline, 4 months, 12 months, and 3 years. Cases of possible neuropathic pain (NP) and persistent-NP were identified using either of 2 definitions: 1) clinical diagnosis of sciatica, 2) self-report version of leeds assessment for neurological symptoms and signs (s-LANSS). Mixed-effects models compared pain intensity (highest of mean leg or mean back pain [0-10 Numerical Rating Scale]) over 3-years between persistent-NP versus non-persistent-NP based on 1) clinical diagnosis, 2) s-LANSS. Logistic regression examined associations between potential prognostic factors and persistent-NP at 4 months based on the 2 NP definitions. At 4-months, using both definitions: 1) approximately 4 out of 10 patients had persistent-NP, 2) mean pain intensity was higher for patients with persistent-NP at all follow-up points compared to those without, 3) only pain self-efficacy was significantly associated with persistent-NP (s-LANSS: OR .98, sciatica: .98), but it did not predict cases of persistent-NP in either multivariable model. Based on factors routinely collected from self-report and clinical examination, it was not possible to predict persistent-NP in this population. PERSPECTIVE: This study provides evidence that neuropathic back-related leg pain in patients consulting in primary care is not always persistent. Patients with persistent neuropathic pain had worse outcomes than those without. Neither leg pain intensity, pain self-efficacy nor MRI scan findings predicted cases of persistent neuropathic pain in this patient population.

A Prospective Study of Sensory Changes in Pediatric Patients After Minimally Invasive Repair of Pectus Excavatum With Cryoablation.

BACKGROUND: Cryoablation during minimally invasive repair for pectus excavatum (MIRPE) reduces opioid use and hospital length of stay. Skin hypoesthesia of the chest wall also occurs. This study sought to determine the frequency, onset, duration, and location of sensory changes and neuropathic pain after cryoablation. METHODS: A prospective study was conducted on patients aged ≤21 years undergoing MIRPE with cryoablation of T3 to T7 dermatomes bilaterally for 120 s at a single institution between March 2021 to December 2022. Patients underwent sensory testing of the chest wall and neuropathic pain surveys (S-LANSS) preoperatively and then postoperatively for 6 months. Incidence and duration of hypoesthesia and neuropathic pain were evaluated. RESULTS: Of 61 patients enrolled in the study, 45 completed evaluations at six months postoperatively. All patients had skin hypoesthesia on postoperative day (POD)1. The mean percentage of the treated anterior chest wall surface area (TACWSA) with hypoesthesia to cold stimulus was 52% (±29.3) on POD 0 and 55% (±19.7) on POD 1. Sensation returned over time, with hypoesthesia affecting 11.1% (±15.5) TACWSA at 6 months. At study completion 58% of patients (26/45) had complete return of sensation; hypoesthesia was found at: 1 dermatome 13% (2/45), 2 dermatomes 22% (11/45), and 3 dermatomes 4% (2/45). Neuropathic pain (S-LANSS ≥12) was documented in 16% (9/55) of patients at hospital discharge but decreased to 6.7% of patients at 6 months. CONCLUSION: Onset of skin hypoesthesia after cryoablation occurred on POD0 and affected 52% of the TACWSA. All patients experienced return of sensation to varying degrees, with 58% experiencing normal sensation in all dermatomes by 6 months. The etiology of persistent hypoesthesia to select dermatomes is unknown but may be related to operative technique or cryoablation. Chronic neuropathic pain is uncommon. LEVEL OF EVIDENCE: II. TYPE OF STUDY: Prognosis Study.

The long-term incidence of chronic post-surgical pain after coronary artery bypass surgery - A prospective observational study.

BACKGROUND: Chronic post-surgical pain (CPSP) represents a significant issue for many patients following surgery; however, the long-term incidence and impact have not been well described following cardiac surgery. Our aim was to characterize CPSP at least 5 years following coronary artery bypass grafting (CABG) surgery. METHODS: This prospective observational study investigated a cohort of patients from a larger trial investigating cognitive outcomes following CABG surgery, with 89 of 148 eligible patients (60.1%) assessed for CPSP at a mean (standard deviation [SD]) of 6.8 [1.2] years. Questionnaires interrogated pain presence, intensity, location, neuropathic characteristics, Geriatric Depression Scale scores (GDS) and instrumental activities of daily living (IADL). RESULTS: CPSP was described in 21/89 (23.6%), with 10 rating it as moderate to severe. Six of the CPSP patients (29%) met criteria for neuropathic pain (6.7% overall). The highest rate of CPSP was associated with the leg surgical site (chest 12/89 [13.5%], arm 8/68 [11.8%] and leg (saphenous vein graft-SVG) 11/37 [29.7%]; χ2 = 6.523, p = 0.038). IADL scores were significantly lower for patients with CPSP (mean [SD]: 36.7 [1.6] vs. no CPSP 40.6 [0.6]; p = 0.006). Patients had GDS scores consistent with moderate depression (GDS >8) in 3/21 (14.3%) with CPSP, versus 3/68 (4.4%) non-CPSP patients (χ2 = 3.20, p = 0.073). CONCLUSIONS: This study identified a CPSP incidence of 23.6% at a mean of 6.8 years after CABG surgery, with the highest pain proportion at SVG harvest sites. CPSP was associated with neuropathic pain symptoms and had a significant impact on IADLs. This emphasizes the need for long-term follow-up of CABG patients. SIGNIFICANCE: This study highlights the impact of CPSP 7 years following cardiac surgery and highlights the effect of surgical site, neuropathic pain and the importance of including pain assessment and management in the long-term follow-up of cardiac surgical patients. Strategies to address and prevent chronic pain following cardiac surgery should be further explored.

Neuropathic Pain After Burn Injury: A Severe and Common Problem in Recovery.

OBJECTIVE: The aim of this study was to address the limited understanding of neuropathic pain (NP) among burn survivors by comprehensively examining its prevalence and related factors on a national scale using the Burn Model System (BMS) National Database. BACKGROUND: NP is a common but underexplored complaint among burn survivors, greatly affecting their quality of life and functionality well beyond the initial injury. Existing data on NP and its consequences in burn survivors are limited to select single-institution studies, lacking a comprehensive national perspective. METHODS: The BMS National Database was queried to identify burn patients responding to NP-related questions at enrollment, 6 months, 12 months, 2 years, and 5 years postinjury. Descriptive statistics and regression analyses were used to explore associations between demographic/clinical characteristics and self-reported NP at different time points. RESULTS: There were 915 patients included for analysis. At discharge, 66.5% of patients experienced NP in their burn scars. Those with NP had significantly higher Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) pain inference, itch, anxiety, depression, and sleep disturbance scores and were less able to partake in social roles. Multiple logistic regression revealed male sex, % total body surface area, and moderate-to-severe pain as predictors of NP at 6 months. At 12 months, % total body surface area and moderate-to-severe pain remained significant predictors, while ethnicity and employment status emerged as significant predictors at 24 months. CONCLUSIONS: This study highlights the significant prevalence of NP in burn patients and its adverse impacts on their physical, psychological, and social well-being. The findings underscore the necessity of a comprehensive approach to NP treatment, addressing both physical symptoms and psychosocial factors.

Effect of use of NSAIDs or steroids during the acute phase of pain on the incidence of chronic pain: a systematic review and meta-analysis of randomised trials.

BACKGROUND: This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain. METHODS: Randomized controlled trials retrieved from nine databases included anti-inflammatory drugs (NSAIDs or steroids) versus non-anti-inflammatory drugs in patients with acute pain and reported the incidence of chronic pain. No specified date, age, sex, or language restrictions. Subgroup analyses were performed according to pain classification, follow-up time, and medication. The GRADE method was used to evaluate quality of evidence. RESULTS: A total of 29 trials (5220 patients) were included. Steroids or NSAIDs did not reduce the incidence of chronic nociceptive pain. Steroid use in acute phase significantly reduced the incidence of chronic neuropathic pain. In subgroup analysis, benefits were observed for methylprednisolone and dexamethasone, with some adverse effects. Steroids or NSAIDs were statistically significant in reducing pain intensity over 1 year, but the effect size was too small, and whether the long-term effect is clinically relevant needs to be further studied. CONCLUSION: Quality of the evidence was low to moderate. No drug can be recommended to prevent chronic nociceptive pain. Injections of steroids (methylprednisolone or dexamethasone) during the acute phase reduce the incidence of chronic neuropathic pain, but most included studies also used local anesthetics. The results are indirect and need to be interpreted with caution. The pooled data effect sizes for pain intensity were small, so the clinical relevance was unclear. Study registration PROSPERO (CRD42022367030).

A systematic review of the prevalence of postamputation and chronic neuropathic pain associated with combat injury in military personnel.

ABSTRACT: Combat trauma can lead to widespread tissue damage and limb loss. This may result in chronic neuropathic and post amputation pain, including phantom limb pain (PLP) and residual limb pain (RLP). The military population is distinct with respect to demographic, injury, and social characteristics compared with other amputation and trauma cohorts. We undertook a systematic review of studies of military personnel, with a history of combat injury, that reported a prevalence of any type of postamputation pain or chronic neuropathic pain, identified from Embase and MEDLINE databases.Using the inverse variance method with a random-effects model, we undertook a meta-analysis to determine an overall prevalence and performed exploratory analyses to identify the effect of the type of pain, conflict, and time since injury on prevalence. Pain definitions and types of pain measurement tools used in studies were recorded. Thirty-one studies (14,738 participants) were included. The pooled prevalence of PLP, RLP, and chronic neuropathic pain were 57% (95% CI: 46-68), 61% (95% CI: 50-71), and 26% (95% CI: 10-54), respectively. Between-study heterogeneity was high (I 2 : 94%-98%). Characterisation of duration, frequency, and impact of pain was limited. Factors reported by included studies as being associated with PLP included the presence of RLP and psychological comorbidity. The prevalence of postamputation pain and chronic neuropathic pain after combat trauma is high. We highlight inconsistency of case definitions and terminology for pain and the need for consensus in future research of traumatic injury.

Predictors of neuropathic dysesthetic pain occurrence and chronification in multiple sclerosis (2-year prospective study).

BACKGROUND: Patients with multiple sclerosis (MS) are a high-risk group for neuropathic pain. OBJECTIVE: to investigate predictors of neuropathic dysesthetic pain (NDP) occurrence and chronification in patients with MS during a 2-year observation period. METHODS: After the exclusion criteria application and signing of informed consent, we recruited in the study 241 patients among which 23 patients prematurely stopped participating in the study. During the 2-year observation period, new NDP was diagnosed on the PainDETECT questionnaire (>18). Patients with newly diagnosed NDP were examined at baseline, in 1, 3, and 6 months depending on pain duration. The socio-demographic, neuropsychological, cognitive, sleep quality, and clinical characteristics of patients were evaluated at the beginning of the study and updated at baseline examination in cases of newly diagnosed NDP. RESULTS: Over a 2-year observation period, NDP occurred in 34 patients (15.6%). Out of 34 cases of newly diagnosed NDP, in 20 cases (58.9%) pain became chronic (lasting longer than 3 months). In the Cox proportional hazards multifactorial model, progressive types of MS were an independent predictor of NDP occurrence (hazard ratio 2.60; 95% confidence interval, 1.30-5.18; p=0.01). In the multifactorial logistic regression analysis, subclinical depressive disorders (according to Hospital Anxiety and Depression Scale) were identified as an independent predictor of NDP chronification (odds ratio 7.14; 95% confidence interval, 1.12-45.59; p=0.04). CONCLUSIONS: In MS predictors of NDP occurrence are progressive types of MS, whereas predictors of NDP chronification are subclinical depressive disorders.

The hidden impact of neuropathic pain after surgical fixation of wrist, hip, and ankle fractures: A cross-sectional retrospective study evaluating its prevalence and risk factors.

BACKGROUND: Dysesthesia, electrical and burning sensations, in addition to allodynia are frequent symptoms of neuropathic pain. Despite the high frequency, scientific data on the development of neuropathic pain after surgery for fracture fixation are scarce. The goal of the present study was to determine the prevalence, risk factors, and evaluate potential associations among neuropathic pain, pain intensity, sociodemographic, and clinical variables after wrist, hip, and ankle fracture fixation. METHODS: A cross-sectional retrospective study involving a cohort of 166 patients who underwent surgery for distal radius, proximal femur, malleolar fracture fixation was performed. Neuropathic pain was assessed one year after fracture fixation using the Doleur Neuropathique Questionnaire (DN4). RESULTS: The incidence of neuropathic pain in our sample was 49 (29.5%). Predictors for the development of neuropathic pain included patients with a high body mass index (BMI), female gender, diabetes mellitus, long-term use of analgesics (especially using pain-modulating medication), patients who presented some fracture-related complication during the course of the treatment, who had limitations for daily activity, and who were away from work due to chronic pain. CONCLUSION: In our study, neuropathic pain after wrist, hip, and ankle fracture fixation was prevalent and associated with higher BMI values and amount of medication, in addition to higher proportions of female sex, absence from work, DM, limitation for daily activities, postoperative complications, and use of pain modulating medications.