Occurrence of somnolence and respiratory depression induced by pregabalin and mirogabalin use and the influence of opioid treatment using the Japanese adverse drug event report database.

Background: Gabapentinoid anticonvulsants are standard treatment for neuropathic pain and are often combined with opioids for treating cancer. It is assumed that this combination may heighten somnolence and respiratory depression due to the inhibitory effects of opioids on the central nervous system. Although pregabalin, a gabapentinoid, is known to increase somnolence frequency during opioid therapy, whether mirogabalin exerts similar effects on somnolence frequency under opioid therapy remains unknown. This study examined the signals of somnolence and respiratory depression in response to pregabalin and mirogabalin use by utilizing data from the Japanese Adverse Drug Event Report database and assessed their interaction with strong opioid analgesics. Methods: Information was obtained from the JADER database from April 2004 to August 2023 via the Pharmaceuticals and Medical Devices Agency website. The study focused on neuropathic pain medications, specifically "pregabalin" and "mirogabalin besilate." Adverse events were defined using preferred terms (PTs) from the Medical Dictionary for Regulatory Activities version 26.1. The PTs considered were "Somnolence (10041349)" and "Respiratory depression (10038678)." To investigate the effect of the combination of strong opioid analgesics with pregabalin and mirogabalin on the occurrence of somnolence, a multivariable logistic regression analysis was conducted. Results: Signals for somnolence were detected with the use of both drugs (pregabalin: information component (IC) [95% confidence intervals (CIs)]: 2.89 [2.70 to 3.08]; mirogabalin: IC [95% CIs] 2.50 [1.85 to 3.16]). When evaluating respiratory depression, a typical and serious adverse event of opioid analgesic use, a signal was detected with pregabalin use but not with mirogabalin use (pregabalin: (IC [95% CIs] 1.28 [0.83 to 1.73]; mirogabalin: IC [95% CIs] -0.15 [-2.20 to 1.89]). Multivariable analysis indicated that the use of strong opioid analgesics increased the occurrence of somnolence when combined with pregabalin but not when combined with mirogabalin (p = 0.004). Conclusion: While the safety of concomitant administation of mirogabalin with opioids remains controversial, caution should be exercised when using pregabalin, especially in combination with opioids for neuropathic pain, compared to that for mirogabalin.

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.

Prevalence of neuropathic pain in patients with symptomatic endometriosis: Assessment using the DN4 score.

The mechanisms underlying pain in cases of endometriosis or chronic pelvic pain are complex, often involving various types of pain; mainly nociceptive pain, central sensitization, and neuropathic pain. Our main objective was to examine the prevalence of neuropathic pain in women with symptomatic endometriosis, and secondary, to explore the factors associated with this type of pain and to assess the prevalence of a positive PPSC score and a history of sexual violence within this population. This study is a retrospective, comparative, single-center cohort study conducted from September 2019 to January 2023. The presence of neuropathic pain was confirmed by a positive DN4 score, defined as greater than or equal to 4. The association with the following variables was studied: age, BMI, marital status, smoking, alcohol and drugs consumption, age at menarche, gestity, parity, duration of exposure to endometriosis, MRI locations, laparoscopy for endometriosis and post-laparoscopy r-ASRM classification, hormone treatment, associated symptoms, VAS, associated pathologies, infertility consultation, Pain Center consultation, EPH-5 score, positive PPSC score (≥5), and history of sexual violence. The prevalence of neuropathic pain was 44.1%. Younger age, being in a relationship, having a high EPH-5 score and undergoing laparoscopy for endometriosis are associated with neuropathic pain independently of other variables. Our study underscores the persistent high prevalence of neuropathic pain in endometriosis cases, emphasizing the importance of actively screening for it. Identifying neuropathic pain could prompt referrals to pain specialists, integrating it into a comprehensive multidisciplinary approach.

Aetiologies of Leg Pain among Patients Presenting to a Vascular Surgery Clinic.

OBJECTIVE: To determine the frequency and pattern of different aetiologies of leg pain among patients visiting vascular surgery clinics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Vascular Surgery Clinics of the Aga Khan University Hospital, Karachi, Pakistan, between February 2021 and June 2023. METHODOLOGY: This study examined patients presenting with leg pain for the first time at vascular surgery clinics. The socio-demographic and clinical data including the clinical symptoms, physical examination findings, and management of leg pain were noted using a specially designed proforma. RESULTS: In a total of 142 patients (200 limbs), 82 (57.7%) were females and 60 (42.3%) were males, with a mean age of 46.8 ± 15.1 years. The patients' mean body mass index (BMI) was 30.2 ± 7.9 kg/m2. Ninety-one (64.1%) patients had a predominantly standing job compared to 51 (35.9%) patients who had a predominantly sitting job. The most common aetiology of leg pain was chronic venous insufficiency (CVI), diagnosed in 107 (53.5%) patients, followed by neurogenic pain [41 (20.5%)], musculoskeletal pain including knee osteoarthritis [30 (15.0%)], and arterial insufficiency [22 (11.0%)].  Conclusion: CVI followed by neuropathic pain was the leading cause of leg pain in vascular surgery clinics at a tertiary care hospital. KEY WORDS: Chronic venous insufficiency, Arterial insufficiency, Vascular surgery, Leg pain, Musculoskeletal pain, Neuralgia.

Understanding Long-Stay Gabapentin Use Increases: A National Nursing Home Clinician Survey on Prescribing Intent.

OBJECTIVES: Explore the indications for long-stay gabapentin use and elucidate the factors spurring the rapid increase in gabapentin prescribing in nursing homes (NHs). METHODS: National cross-sectional survey of NH prescribers distributed anonymously using SurveyMonkey. Sampling for convenience was obtained through crowdsourcing, leveraging collaborations with NH clinician organizations. Developed by a multidisciplinary team, pilot data/existing literature informed survey content. RESULTS: A total of 131 surveys completed. Participants: 71% white, 52% female, 71% physicians. Off-label gabapentin prescribing was ubiquitous. Nearly every clinician used gabapentin for neuropathic pain, most for any form of pain. Many clinicians also prescribe gabapentin to moderate psychiatric symptoms and behaviors. Clinicians' prescribing was influenced by opioid, antipsychotic, and anxiolytic reduction policies because gabapentin was perceived as an unmonitored and safer alternative. CONCLUSIONS: Off-label gabapentin increases are closely linked to opioid reduction efforts as more NH clinicians utilize gabapentin as an unmonitored opioid alternative. Our results highlight, however, the less recognized significance of long-stay prescribing for psychiatric symptoms and the similar contribution of psychotropic reduction initiatives, a phenomenon warranting further scrutiny. CLINICAL IMPLICATIONS: Clinicians perceive gabapentin as safer than the drugs it is replacing. Whether this is true remains unclear; the individual- and population-level risks of increased gabapentin use are largely unknown.

Current trends in the medical treatment of neuropathic low back pain: a Swedish registry-based study of 1.7 million people.

BACKGROUND: Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational registry-based study describes the current trends in the medical treatment of neuropathic low back pain in the Swedish region of Västra Götaland, which has a population of 1.7 million. The study aims to; (1) identify the prevalence of neuropathic low back pain within the study population; (2) to explore the patterns of medical treatment utilization, including the prevalence and distribution of opioids (OG) and analgesics specified for neuropathic low back pain (NG) and (3) to evaluate the long-term trends and changes in medical treatment practice for neuropathic low back pain over the study period. METHODS: This study includes a descriptive analysis of aggregated data extracted from the Swedish primary care registry VEGA and the pharmaceutical prescription registry Digitalis between the years 2017 and 2021. The data were stratified by year, age, gender, pharmaceutical code (ATC), and sub-diagnoses and presented as the prevalence of unique patients retrieving prescribed medication within six months before or after a registered diagnosis of neuropathic low back pain. The pharmaceutical codes were furthermore grouped into two groups depending on their mechanism of action; opioid group (OG) and neuropathic group (NG). RESULTS: In all four diagnosis groups, more patients used opioid analgesics than neuropathic analgesics. The greatest difference between the opioid group and neuropathic group was in the lumbar spinal stenosis diagnosis group (67.1% vs. 40.6%), followed by the lumbar root canal stenosis diagnosis (65.9% vs. 44.2%), the nerve root and plexus compressions in intervertebral disc disorders diagnosis (57.5% vs. 40.8%), and lumbago with sciatica diagnosis (38.4% vs. 22.7%). CONCLUSIONS: The trends suggest a general increase in the prescription rate and therefore patients' use of neuropathic analgesics for neuropathic pain associated with the studied diagnoses. However, opioid treatment remains the most common. The results indicate that the treatment for neuropathic low back pain needs to be improved.

Prevalence of radicular neuropathic pain in idiopathic Parkinson's disease: A systematic review and meta-analysis.

Parkinson's disease (PD) is estimated to impact up to 1 % of the global population aged 60 years and older. Among the non-motor manifestations of idiopathic PD, radicular neuropathic pain emerges as a noteworthy concern due to its potential for debility in affected individuals. In, this systematic review and meta-analysis we aimed to evaluate the prevalence of radicular neuropathic pain and thus provide evidence of how this painful symptom affects the lives of patients with idiopathic PD. We registered the research protocol for this study in PROSPERO (CRD42022327220). We searched the Embase, Scopus, and PubMed platforms for studies on PD and neuropathic pain until April 2023. The search yielded 36 articles considered to have a low risk of bias. The prevalence of radicular neuropathic pain in patients with PD was 12.7 %, without a difference when we consider the duration of diagnosis (cut-off < 7 years) or levodopa dosage (cut-off <600 mg/dL). Moreover, there was no variation in the prevalence of radicular neuropathic pain regarding a Hoehn and Yahr stage cut-off of <2.5 or >2.5. Of note, a limited number of patients received pain treatment (21.5 %). We also found that the source of publication bias is the use of the Ford criteria (FC), suggesting that this type of diagnostic criteria may contribute to an underdiagnosis of radicular neuropathic pain in patients with PD. This study underlines the necessity for a more discerning and comprehensive approach to the diagnosis and management of radicular neuropathic pain in patients with idiopathic PD.

Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment.

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.

Radiation-induced Chronic Pain Plagues Head and Neck Cancer Survivors: A Cross-sectional Analysis From the Cohort in Radiotherapy-related Nervous System Complications.

The epidemiology and prognosis of radiation-induced chronic pain, especially chronic neuropathic pain (CNP), are the understudied domain among head and neck cancer (HNC) survivors after radiotherapy (RT). This study aimed to estimate the prevalence of such chronic pain, and explore its correlations with mental health, sleep disorders, cognitive function, and quality of life (QOL) within these patients. This research encompassed HNC survivors post RT. The determination of radiation-induced chronic pain and CNP adhered to the guidelines outlined by the International Association for the Study of Pain. Multivariable regression analyses were employed to explore the relationship between pain and anxiety, depression, sleep disturbances, cognitive function, and QOL. A total of 1,071 HNC survivors post RT were included in this study. The prevalence of radiation-induced chronic pain was 67.1%, and the prevalence of RT-associated CNP was 38.3%. Compared with those reporting no pain, patients with radiation-induced chronic pain had a significantly increased risk of anxiety, depression, and sleep disorders (all P < .001). And there was a significantly negative association between chronic pain and QOL across physiological (P < .001), psychological (P < .001), social relationships (P = .001), and environmental (P = .009) domains. Compared with non-CNP, patients with RT-related CNP had a higher risk of anxiety (P = .027) and sleep disorders (P = .013). The significantly negative associations were found between CNP and the physiological (P = .001), psychological (P = .012), and social score (P = .035) in World Health Organisation Quality of Life Assessment-Bref. This study underscores the substantial prevalence of chronic pain, particularly CNP, and its potential impact on the mental health, sleep, and QOL among HNC survivors post RT. PERSPECTIVE: This study highlights the high prevalence of radiation-induced chronic pain and CNP, and their potential impacts on anxiety, depression, sleep, and QOL among the HNC survivors. Clinically, these findings have important implications for improving the care and outcomes of HNC survivors.

After 4 years of survival, patients treated for an oral or oropharyngeal cancer have more neurosensorial disorders than chronic pain and a better quality of life.

PURPOSE: During follow-up, patients in remission after oral or oropharyngeal cancer are few to express pain, depression or anxiety, their chief complain are dry mouth and difficulties to chewing. The aim of the study is to estimate prevalence of pain, quality of life and their evolution over four years. METHODS: This prospective observational study included 21 patients between June and September 2017. Clinical examination, neurosensory examination and questionnaires (using visual analogic scale DN4, PCS-CF, HADS EORTC QLQ30 and H&N 35) were performed and a second time 4 years later. RESULTS: After 4 years, 17 patients could be reviewed. In 2017 as in 2021, two patients (11.8 %) experience neuropathic pain. In 2017, 14 (82.3 %) reported paresthesia or dysesthesia or hypo/anesthesia, none of them have provoked pain to a mechanical or thermal stimulus. In 2021, only 9 (53 %) still report those symptoms. Global analysis of the questionnaire QLQC30 reveals a significant increase quality of life of all 17 patients (p = 0.0003). For the two questionnaires QLQC30 and QLQ-H&N 35, dry mouth, sticky saliva, difficulties for eating and relation with food, are strong grievances which an absence of amelioration or a degradation. CONCLUSIONS: Neurosensory disturbance is a frequent symptom but pain concerns only 11.8 % of patients. Quality of life increase globally, yet difficulties concerning oral cavity functions endure. IMPLICATIONS FOR CANCER SURVIVORS: For remission patients, pain is an unfrequent situation unlike neurosensory disturbance. Support care improve life quality. In case of onset of pain, recurrence and osteoradionecrosis should be mentioned immediately.

Prevalence and patterns of neuropathic pain in people with chronic post-surgical pain after total knee arthroplasty.

Aims: The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA). Methods: Between 2016 and 2019, 363 patients with troublesome pain, defined as a score of ≤ 14 on the Oxford Knee Score pain subscale, three months after TKA from eight UK NHS hospitals, were recruited into the Support and Treatment After Replacement (STAR) clinical trial. Self-reported neuropathic pain and postoperative pain was assessed at three, nine, and 15 months after surgery using the painDETECT and Douleur Neuropathique 4 (DN4) questionnaires collected by postal survey. Results: Symptoms of neuropathic pain were common among patients reporting chronic pain at three months post-TKA, with half reporting neuropathic pain on painDETECT (191/363; 53%) and 74% (267/359) on DN4. Of those with neuropathic pain at three months, half continued to have symptoms over the next 12 months (148/262; 56%), one-quarter had improved (67/262; 26%), and for one-tenth their neuropathic symptoms fluctuated over time (24/262; 9%). However, a subgroup of participants reported new, late onset neuropathic symptoms (23/262; 9%). Prevalence of neuropathic symptoms was similar between the screening tools when the lower cut-off painDETECT score (≥ 13) was applied. Overall, mean neuropathic pain scores improved between three and 15 months after TKA. Conclusion: Neuropathic pain is common in patients with chronic pain at three months after TKA. Although neuropathic symptoms improved over time, up to half continued to report painful neuropathic symptoms at 15 months after TKA. Postoperative care should include screening, assessment, and treatment of neuropathic pain in patients with early chronic postoperative pain after TKA.

Phenotyping of chronic pain in breast cancer survivors: an original study using the cancer pain phenotyping (CANPPHE) Network multidisciplinary international guidelines.

PURPOSE: The primary aim of this cross-sectional study is to examine the prevalence of pain phenotypes in breast cancer survivors (BCS). A secondary aim entails examining whether health related quality of life differs between the main pain phenotypes in BCS. METHODS: BCS who experienced chronic pain were asked to complete the numeric pain rating scale for pain, Margolis pain diagram, and short form 36 (SF-36). Following administration of questionnaires and quantitative sensory examinations were applied. To determine the prevalence of the predominant type of pain, a recently proposed classification system by the Cancer Pain Phenotyping (CANPPHE) Network was used. RESULTS: Of the 86 female participants, 19 (22.09%) had dominant neuropathic pain, 18 (20.93%) had dominant nociceptive pain and 14 (16.28%) had dominant nociplastic pain. 35 participants (40.70%) were classified as having mixed pain. One-way ANOVA revealed a significant difference between the four pain groups for the SF-36 general health (F = 3.205, p = 0.027), social functioning (F = 4.093, p = 0.009), and pain (F = 3.603, p = 0.017) subscale scores. CONCLUSION: This study found that pain in BCS was mostly of mixed phenotype, followed by predominantly neuropathic and nociplastic pain. Furthermore, it was found that, compared to BCS with predominant neuropathic and nociceptive pain, BCS with predominant nociplastic pain have lower health related quality of life in the areas of bodily pain and social functioning.

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.

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.

Age and Sex Differences in Pediatric Neuropathic Pain and Complex Regional Pain Syndrome: A Scoping Review.

BACKGROUND: Age and sex differences may exist in the frequency (incidence, prevalence) or symptoms of neuropathic pain (NP) and complex regional pain syndrome (CRPS) due to biopsychosocial factors (eg, neurodevelopment, physiological and hormonal changes, psychosocial differences) that evolve through childhood and adolescence. Age and sex differences may have implications for evaluating screening and diagnostic tools and treatment interventions. OBJECTIVE: To map the existing literature on pediatric NP and CRPS with respect to age and sex distributions, and age and sex differences in symptomology and frequency. METHODS: A scoping literature review was conducted. Databases were searched from inception to January 2023. Data were collected on study design, setting, demographics, and age and sex differences in frequency and symptoms. RESULTS: Eighty-seven studies were included. Distribution of participants with CRPS (n=37 studies) was predominantly early adolescence (10 to 14 y) and female sex, while NP (n=42 studies) was most commonly reported throughout adolescence (10 to 19 y) in both sexes. Forty-one studies examined age and sex differences in frequency; 6 studies reported higher frequency in adolescence. Very few studies (n=11) examined differences in symptomology. DISCUSSION: Large epidemiological studies are required to further understand age and sex differences in frequency of pediatric NP and CRPS. Age and sex differences must be considered when evaluating screening and diagnostic tools and treatment interventions to ensure relevance and validity to both sexes and across ages. Validated tools will improve understanding of age-dependent and sex-dependent differences in symptoms, pathophysiology, and psychosocial impact of pediatric NP and CRPS.

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, 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.

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.