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INTRODUCTION: This study explores the interaction between cytokines, cell-mediated immunity (T cells, B cells, and NK cells), and prolonged morphine administration in chronic neuropathic pain patients without cancer-related issues. Despite evidence of opioid immunomodulation, few studies have compared these interactions. METHODS: In a cross-sectional and comparative study, 50 patients with chronic low back radicular pain ("Failed Back Surgery Syndrome") were categorized into intrathecal morphine infusion (IT group, n = 18), oral morphine (PO group, n = 17), and non-opioid treatment (NO group, n = 15). Various parameters, including plasma and cerebrospinal fluid (CSF) cytokine concentrations, lymphocyte immunophenotyping, opioid escalation indices, cumulative morphine dose, and treatment duration, were assessed. RESULTS: CSF IL-8 and IL-1ß concentrations exceeded plasma levels in all patients. No differences in T, B, and NK lymphocyte numbers were observed between morphine-treated and non-treated patients. Higher plasma IL-5 and GM-CSF concentrations were noted in IT and PO groups compared to NO. CSF IFNγ concentrations were higher in PO and NO than IT. Positive correlations included CD4 concentrations with opioid escalation indices, and negative correlations involved NK cell concentrations, CSF TNFα concentrations, and opioid escalation indices. Positive correlations were identified between certain cytokines and pain intensity in IT patients, and between NK cells and cumulative morphine dose. Negative correlations were observed between CSF IL-5 concentrations and pain intensity in IT and PO, and between opioid escalation indices and CSF cytokine concentrations in PO and IT. CONCLUSION: Associations between cytokines, cellular immunity, and prolonged morphine treatment, administered orally and intrathecally were identified.

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OBJECTIVES: Altered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. METHODS: This was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. RESULTS: Twenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). CONCLUSION: Our preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

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OBJECTIVE: The aim of this study was to provide geographic comparisons of deep brain stimulation (DBS) procedures in Latin America with the US and Europe regarding primary indications, demographic information, clinical and device-related adverse events, technology used, and patient outcomes using the Medtronic Product Surveillance Registry data as of July 31, 2021. METHODS: Two thousand nine hundred twelve patients were enrolled in the registry (2782 received DBS and 1580 are currently active). Fourteen countries contributed 44,100 years of device experience to the registry. DBS centers in Latin America are located in Colombia (n = 3), Argentina (n = 1), Brazil (n = 1), and Mexico (n = 1). Fisher's exact test was used to compare the difference in proportions of categorical variables between regions. The Wilcoxon signed-rank test was used for the EQ-5D index score change from baseline to follow-up. RESULTS: The most common indication for DBS was Parkinson's disease across all regions. In Latin America, dystonia was the second most common indication, compared to essential tremor in other regions. There was a striking finding with respect to age-patients were an average of 10 years younger at DBS implantation in Latin America. This difference was most likely due to the greater number of patients with dystonia receiving the device implants. The intraoperative techniques were quite similar, showing the same level of quality and covering the main principles of the surgeries with some variations in the brand of frames, planning software, and microrecording systems. Rechargeable batteries were significantly more common in Latin America (72.37%) than in the US (6.44%) and Europe (9.9%). Staging of the DBS procedure differed, with only 11.84% in Latin America staging the procedure compared with 97.58% and 34.86% in the US and Europe, respectively. The EQ-5D score showed significant improvements in all regions during the first 6-12 months (p < 0.0001). However, the 24-month follow-up only showed an improvement in the scale for Latin America (p < 0.0001). CONCLUSIONS: DBS was performed in Latin America with similar indications, techniques, and technology as in the US and Europe. Important differences were found, with Latin America implementing more regular use of rechargeable devices, including younger patients at the time of surgery, and showing more sustained quality of life improvements at 24 months of follow-up. The authors hypothesize that these disparities stem from differences in resources among regions. However, more studies are needed to standardize DBS practice across the world to improve patients' quality of life and provide high-quality care.

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Neuropathic pain occurs in people experiencing lesion or disease affecting the somatosensorial system. It is present in 7 % of the general population and may not fully respond to first- and second-line treatments in up to 40 % of cases. Neuromodulation approaches are often proposed for those not tolerating or not responding to usual pharmacological management. These approaches can be delivered surgically (invasively) or non-invasively. Invasive neuromodulation techniques were the first to be employed in neuropathic pain. Among them is spinal cord stimulation (SCS), which consists of the implantation of epidural electrodes over the spinal cord. It is recommended in some guidelines for peripheral neuropathic pain. While recent studies have called into question its efficacy, others have provided promising data, driven by advances in techniques, battery capabilities, programming algorithms and software developments. Deep brain stimulation (DBS) is another well-stablished neuromodulation therapy routinely used for movement disorders; however, its role in pain management remains limited to specific research centers. This is not only due to variable results in the literature contesting its efficacy, but also because several different brain targets have been explored in small trials, compromising comparisons between these studies. Structures such as the periaqueductal grey, posterior thalamus, anterior cingulate cortex, ventral striatum/anterior limb of the internal capsule and the insula are the main targets described to date in literature. SCS and DBS present diverse rationales for use, mechanistic backgrounds, and varying levels of support from experimental studies. The present review aims to present their methodological details, main mechanisms of action for analgesia and their place in the current body of evidence in the management of patients with neuropathic pain, as well their particularities, effectiveness, safety and limitations.

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BACKGROUND: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment. OBJECTIVES: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders. METHODS: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition. RESULTS: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group). DISCUSSION: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society.

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Citrus leprosis is the most important viral disease affecting citrus. The disease is caused predominantly by CiLV-C and is transmitted by Brevipalpus yothersi Baker mites. This study brings some insight into the colonization of B. yothersi in citrus [(Citrus × sinensis (L.) Osbeck (Rutaceae)] previously infested by viruliferous or non-viruliferous B. yothersi. It also assesses the putative role of shelters on the behavior of B. yothersi. Expression of PR1 and PR4 genes, markers of plant defense mechanisms, were evaluated by RT-qPCR to correlate the role of the plant hormonal changes during the tri-trophic virus-mite-plant interplay. A previous infestation with either non-viruliferous and viruliferous mites positively influenced oviposition and the number of adult individuals in the resulting populations. Mite populations were higher on branches that had received a previous mite infestation than branches that did not. There was an increase in the expression of PR4, a marker gene in the jasmonic acid (JA) pathway, in the treatment with non-viruliferous mites, indicating a response from the plant to their feeding. Conversely, an induced expression of PR1, a marker gene in the salicylic acid (SA) pathway, was observed mainly in the treatment with viruliferous mites, which suggests the activation of a plant response against the pathogen. The earlier mite infestation, as well as the presence of leprosis lesions and a gypsum mixture as artificial shelters, all fostered the growth of the B. yothersi populations after the second infestation, regardless of the presence or absence of CiLV-C. Furthermore, it is suggested that B. yothersi feeding actually induces the JA pathway in plants. At the same time, the CiLV-C represses the JA pathway and induces the SA pathway, which benefits the mite vector.

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BACKGROUD: Diabetic neuropathy (DN) is one of the most common complications of diabetes, affecting about half of individuals with the disease. Among the various symptoms of DN, the development of chronic pain stands out and manifests as exacerbated responses to sensorial stimuli. The conventional clinical treatments used for general neuropathy and associated painful symptoms, still brings uncomplete and unsatisfactory pain relief. Patients with neuropathic pain syndromes are heterogeneous. They present with a variety of sensory symptoms and pain qualities which difficult the correct diagnosis of sensory comorbidities and consequently, the appropriate chronic pain management. AIMS: Herein, we aimed to demonstrate the existence of different sensory profiles on diabetic patients by investigating epidemiological and clinical data on the symptomatology of a group of patients with DN. METHODS: This is a longitudinal and observational study, with a sample of 57 volunteers diagnosed with diabetes from outpatient day clinic of Hospital Universitário of the University of São Paulo-Brazil. After being invited and signed the Informed Consent Form (ICF), patients were submitted to clinical evaluation and filled out pain and quality of life questionnaires. They also performed quantitative sensory test (QST) and underwent skin biopsy for correlation with cutaneous neuropathology. RESULTS: Data demonstrate that 70% of the studied sample presented some type of pain, manifesting in a neuropathic or nociceptive way, what has a negative impact on the life of patients with DM. We also demonstrated a positive association between pain and anxiety and depression, in addition to pain catastrophic thoughts. Three distinct profiles were identified in the sample, separated according to the symptoms of pain: (i) subjects without pain; (ii) with mild or moderate pain; (iii) subjects with severe pain. We also identified through skin biopsy that diabetic patients presented advanced sensory impairment, as a consequence of the degeneration of the myelinated and unmyelinated peripheral fibers. This study characterized the painful symptoms and exteroceptive sensation profile in these diabetic patients, associated to a considerable level of sensory degeneration, indicating, and reinforcing the importance of the long-term clinical monitoring of individuals diagnosed with DM, regarding their symptom profiles and exteroceptive sensitivity.

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Electron microscopy has become increasingly essential as an investigative research resource in various fields of science. Despite the evolution of the equipment and preparation techniques, little has been published on techniques for affixation and removal of samples on the stubs after analysis. This work aims to illustrate a quick and low-cost procedure for fixing and removing a sample from the support for analysis by electronic microscopy, applied to crustacean and insect species, as well as other invertebrates. It thus makes it feasible to use specimens or anatomical portions of specimens represented by a few individuals, or designated as paratypes or holotypes in a collection. RESEARCH HIGHLIGHTS: This study presents a quick and low-cost procedure for fixing and removing samples from support for electron microscopy analysis. This technique makes it possible to use individual specimens or anatomical portions represented in a collection. Fluidization of the adhesive and its complete removal allow easy recovery and repositioning of samples.

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Many mites of the family Eriophyidae are important pests worldwide. In citrus crops, the eriophyid Phyllocoptruta oleivora stands out for the economic losses caused. The pest's injuries cause the darkening of leaves, twigs, and fruits, making them unfit for the fresh fruit market and affecting plant productivity. Another species that causes similar symptoms was described in Brazil recently, the brown citrus rust mite, Tegolophus brunneus. Although studies have not been performed with this species, growers and technicians have attributed the rise in rust damages in Brazil to T. brunneus, affirming that this mite is more aggressive and resistant to acaricides than P. oleivora. In this study, the distribution of T. brunneus in the main Brazilian citrus belt and the differential toxicity of the acaricides sulfur and abamectin were evaluated for both species. Infested fruits were collected from different orchards in many municipalities, covering the main citrus species and cultivars grown, aiming to show the main T. brunneus hosts. It was observed that only plants of Tahiti acid lime (Citrus latifolia) were infested by T. brunneus, whereas P. oleivora infested all citrus cultivars and species evaluated (Citrus spp.). In our study, T. brunneus and P. oleivora were never observed coinfesting the same fruit/leaf or plant. The acute toxicity test of sulfur and abamectin as acaricides showed that T. brunneus has greater tolerance to abamectin than P. oleivora. However, the acute toxicity of sulfur was similar for both species. These results showed T. brunneus specificity to infest Tahiti acid lime, causing important damage to this crop, and suggest that attention should be paid to managing this mite using abamectin.

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Background: Conventional thoracotomy (CT) often leads to systemic inflammatory response syndrome (SIRS), which induces several clinical complications. CT remains widely used in low-income institutions. Although minimally invasive surgical procedures, such as robotic surgery (RS), have been used to prevent many of the complications inherit from the surgical procedure. Here, we investigated the protective effect of vagus nerve stimulation (VNS) in a pre-clinical model during CT or RS and postoperative period (POP) relative to clinical complications and inflammatory control. The objective was to compare hemodynamic features and cytokine levels in the blood, lung, and bronchoalveolar lavage (BAL) fluids of animals subjected to CT or RS with or without VNS. Methods: Twenty-four minipigs were subjected to 12 animals CT and 12 animals RS, with or without VNS, and accompanied 24 h later by pulmonary lobectomy. Blood samples for evaluating the hemodynamic parameters were collected before the surgical preparation, immediately after the beginning of VNS, and every 4 h until 24 h after the lobectomy. BAL fluid and lung tissue were collected at the end of the experiment. Cytokine levels were evaluated in the blood, BAL fluid, and lung tissues. Results: VNS maintained a more stable heart rate during POP and decreased the incidence of overall cardiac complications while preventing increase in IL-6 levels 12 h after lobectomy, compared to sham animals. No differences were found in cytokine expression in the BAL fluid and lung tissue in any of the studied groups. Conclusions: Taken together, our data suggested that VNS should be considered a non-pharmacological tool in the prevention of the exacerbated inflammatory response responsible for severe clinical complications, especially in more aggressive surgical procedures.

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Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = -.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PERSPECTIVE: This work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.

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Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a food and waterborne pathogen with severe public health implications. We report the first-time isolation of this pathogen in the Central Highlands of Peru through standardized culture procedures and polymerase chain reaction (PCR). Escherichia coli strains were cultured from rectal-anal swabs from dairy calves and beef from food markets. The latex agglutination test was used to detect O157 and H7 antigens, and multiplex real-time PCR was carried out to detect virulence-related genes. The STEC O157:H7 strains were isolated from 3.5% (1/28) of beef samples and from 6.0% (3/50) of dairy calves that also carried both eaeA and stx1 genes. Therefore, this pathogen is a potential cause of food/waterborne disease in the region, and its surveillance in both livestock and their products should be improved to characterize the impact of its zoonotic transmission. From 2010 to 2020, E. coli was suspected in 10 outbreaks reported to the Peruvian Ministry of Health. Isolates from future outbreaks should be characterized to assess the burden posed by STEC O157:H7 in Peru.

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Brachytydeus juanjosei sp. nov., a new species of Neotropical Tydeidae, is illustrated and described from females, males, and a tritonymph collected from the leaves of a native forest tree, Neltuma piurensis (Fabaceae), from Department of Piura in north-western Peru. The new tydeid mite was found all year long, but more frequently observed during spring in high populations (September/December). A key to the known Peruvian species of the subfamily Tydeinae is provided.

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Brazilian biodiversity is still poorly studied, especially in the northeast region of Brazil. In the state of Maranhão, the rich fauna is still under-explored in relation to the Cladocera, and this geographic area covers four biomes, which makes it an important field of research on the Cladocera community. In this work, the record of three species is reported: Dadaya macrops Sars, 1901 first record of the genus for the state, Simocephalus serrulatus (Koch, 1841) and Simocephalus latirostris (Stingelin, 1906). The work presents brief descriptions and illustrations of the morphology of the studied species.

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ABSTRACT BACKGROUND AND OBJECTIVES: Conventional electrodiagnostic studies (EDX) are frequently used to support the diagnosis of peripheral neuropathic pain. However, routine EDX has poor diagnostic yield for identifying small fiber neuropathy, which may be cause of neuropathic pain in some patients. This study aimed to assess the gain in diagnostic yield brought by adding pain-related evoked potentials with concentric electrode (CN-PREP) and nociceptive withdrawal reflex (NWR) assessments to EDX. METHODS: Transversal observational accuracy study which included patients referred to routine EDX in a tertiary-care hospital who reported chronic neuropathic pain in their lower limbs. Besides routine EDX, subjects underwent CN-PREP and NWR assessments. Diagnostic yield and tolerability were examined and compared between test studies. RESULTS: The study enrolled 100 patients (54% female), with 57 ± 12 years. EDX was altered in 47% of all patients. The addition of CN-PREP alone, and NWR combined with CN-PREP increased diagnostic yield to 69% and 72%, respectively. CN-PREP proved to be well tolerable, while NWR was associated with higher test-related pain intensity and discontinuation rate (9% vs. 0%). Considering EDX as the reference test, CN-PREP sensitivity was 85.1% and specificity 58.5%. CONCLUSION: Combining CN-PREP with the routine EDX for patients with neuropathic pain is feasible and results in increased diagnostic yield. Conversely, the addition of NWR to the aforementioned tests provides little improvement to this yield and is less tolerable to the patient. Further studies are needed to determine the actual sensitivity and specificity of CN-PREP when compared to the gold-standard for small fiber neuropathy diagnosis, i.e. intraepidermal nerve fiber density assessment.

RESUMO JUSTIFICATIVA E OBJETIVOS: Estudos convencionais de eletrodiagnóstico (EDX) são frequentemente usados para apoiar o diagnóstico de dor neuropática periférica. No entanto, o EDX de rotina tem baixo rendimento diagnóstico para identificar neuropatia de pequenas fibras. O objetivo deste estudo foi avaliar o ganho no rendimento diagnóstico pela adição de avaliações de potenciais evocados relacionados à dor com eletrodo concêntrico (CN-PREP) e reflexo de retirada nociceptiva (NWR) ao EDX. MÉTODOS: Estudo de precisão observacional transversal que incluiu pacientes encaminhados para EDX de rotina com dor neuropática crônica em membros inferiores. Além do EDX de rotina, os indivíduos foram submetidos às avaliações CN-PREP e NWR. O rendimento diagnóstico e a tolerabilidade foram examinados e comparados entre os estudos de teste. RESULTADOS: O estudo envolveu 100 pacientes (54% mulheres), com 57 ± 12 anos. O EDX estava alterado em 47%. A adição de CN-PREP sozinho e NWR combinado com CN-PREP aumentou o rendimento diagnóstico para 69% e 72%, respectivamente. O CN-PREP provou ser bem tolerável, enquanto o NWR foi associado a maior intensidade de dor relacionada ao teste e taxa de descontinuação (9% vs. 0%). Considerando o EDX como teste de referência, a sensibilidade do CN-PREP foi de 85,1% e a especificidade de 58,5%. CONCLUSÃO: A combinação do CN-PREP com o EDX de rotina para pacientes com dor neuropática é viável e resulta em maior rendimento diagnóstico. Já a adição de NWR aos testes mencionados fornece pouca melhora nesse rendimento e é menos tolerável para o paciente. Mais estudos são necessários para determinar a real sensibilidade e especificidade do CN-PREP quando comparado ao padrão-ouro para diagnóstico de neuropatia de pequenas fibras, ou seja, a avaliação da densidade de fibras nervosas intraepidérmicas.

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BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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OBJECTIVES: It is not known whether cortical plastic changes reported in low-back pain (LBP) are present in all etiologies of LBP. Here we report on the assessment of patients with three LBP conditions: non-specific-LBP (ns-LBP), failed back surgery syndrome (FBSS), and sciatica (Sc). METHODS: Patients underwent a standardized assessment of clinical pain, conditioned pain modulation (CPM), and measures of motor evoked potential (MEPs)-based motor corticospinal excitability (CE) by transcranial magnetic stimulation, including short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Comparisons were also made with normative data from sex- and age-matched healthy volunteers. RESULTS: 60 patients (42 women, 55.1±9.1 years old) with LBP were included (20 in each group). Pain intensity was higher in patients with neuropathic pain [FBSS (6.8±1.3), and Sc (6.4±1.4)] than in those with ns-LBP (4.7±1.0, P<0.001). The same was shown for pain interference (5.9±2.0, 5.9±1.8, 3.2±1.9, P<0.001), disability (16.4±3.3, 16.3±4.3, 10.4±4.3, P<0.001), and catastrophism (31.1±12.3, 33.0±10.4, 17.4±10.7, P<0.001) scores for FBSS, Sc, and ns-LBP groups, respectively. Patients with neuropathic pain (FBSS, Sc) had lower CPM (-14.8±1.9, -14.1±16.7, respectively) compared to ns-LBP (-25.4±16.6; P<0.02). 80.0% of the FBSS group had defective ICF compared to the other two groups (52.5% for ns-LBP, P=0.025 and 52.5% for Sc, P=0.046). MEPs (140%-rest motor threshold) were low in 50.0% of patients in the FBSS group compared to 20.0% of ns-LBP (P=0.018) and 15.0% of Sc (P=0.001) groups. Higher MEPs were correlated with mood scores (r=0.489), and with lower neuropathic pain symptom scores(r=-0.415) in FBSS. CONCLUSIONS: Different types of LBP were associated with different clinical, CPM and CE profiles, which were not uniquely related to the presence of neuropathic pain. These results highlight the need to further characterize patients with LBP in psychophysics and cortical neurophysiology studies.

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BACKGROUND: It is unknown if different etiologies or lesion topographies influence central neuropathic pain (CNP) clinical manifestation. METHODS: We explored the symptom-somatosensory profile relationships in CNP patients with different types of lesions to the central nervous system to gain insight into CNP mechanisms. We compared the CNP profile through pain descriptors, standardized bedside examination, and quantitative sensory test in two different etiologies with segregated lesion locations: the brain, central poststroke pain (CPSP, n = 39), and the spinal cord central pain due to spinal cord injury (CPSCI, n = 40) in neuromyelitis optica. RESULTS: Results are expressed as median (25th to 75th percentiles). CPSP presented higher evoked and paroxysmal pain scores compared to CPSCI (p < 0.001), and lower cold thermal limen (5.6°C [0.0-12.9]) compared to CPSCI (20.0°C [4.2-22.9]; p = 0.004). CPSCI also had higher mechanical pain thresholds (784.5 mN [255.0-1078.0]) compared to CPSP (235.2 mN [81.4-1078.0], p = 0.006) and higher mechanical detection threshold compared to control areas (2.7 [1.5-6.2] vs. 1.0 [1.0-3.3], p = 0.007). Evoked pain scores negatively correlated with mechanical pain thresholds (r = -0.38, p < 0.001) and wind-up ratio (r = -0.57, p < 0.001). CONCLUSIONS: CNP of different etiologies may present different pain descriptors and somatosensory profiles, which is likely due to injury site differences within the neuroaxis. This information may help better design phenotype mechanism correlations and impact trial designs for the main etiologies of CNP, namely stroke and spinal cord lesions. This study provides evidence that topography may influence pain symptoms and sensory profile. The findings suggest that CNP mechanisms might vary according to pain etiology or lesion topography, impacting future mechanism-based treatment choices.

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BACKGROUND: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. METHODS: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. RESULTS: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. CONCLUSIONS: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. SIGNIFICANCE: COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.

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OBJECTIVES: Central neuropathic pain (CNP) is associated with altered corticomotor excitability (CE), which can potentially provide insights into its mechanisms. The objective of this study is to describe the CE changes that are specifically related to CNP. METHODS: We evaluated CNP associated with brain injury after stroke or spinal cord injury (SCI) due to neuromyelitis optica through a battery of CE measurements and comprehensive pain, neurological, functional, and quality of life assessments. CNP was compared to two groups of patients with the same disease: i. with non-neuropathic pain and ii. without chronic pain, matched by sex and lesion location. RESULTS: We included 163 patients (stroke=93; SCI=70: 74 had CNP, 43 had non-neuropathic pain, and 46 were pain-free). Stroke patients with CNP had lower motor evoked potential (MEP) in both affected and unaffected hemispheres compared to non- neuropathic pain and no-pain patients. Patients with CNP had lower amplitudes of MEPs (366 µV ±464 µV) than non-neuropathic (478 ±489) and no-pain (765 µV ± 880 µV) patients, p < 0.001. Short-interval intracortical inhibition (SICI) was defective (less inhibited) in patients with CNP (2.6±11.6) compared to no-pain (0.8±0.7), p = 0.021. MEPs negatively correlated with mechanical and cold-induced allodynia. Furthermore, classifying patients' results according to normative data revealed that at least 75% of patients had abnormalities in some CE parameters and confirmed MEP findings based on group analyses. DISCUSSION: CNP is associated with decreased MEPs and SICI compared to non-neuropathic pain and no-pain patients. Corticomotor excitability changes may be helpful as neurophysiological markers of the development and persistence of pain after CNS injury, as they are likely to provide insights into global CE plasticity changes occurring after CNS lesions associated with CNP.

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