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Clinical studies on neuromodulation intervention for trigeminal neuralgia have not yet shown promising results. This might be due to the fact that the pathophysiology of chronic trigeminal neuropathy is not yet fully understood. Chronic trigeminal neuropathy includes trigeminal autonomic neuropathy, painful trigeminal neuropathy, and persistent idiopathic facial pain. This disorder is caused by complex abnormalities in the pain processing system, which is comprised of the affective, emotional, and sensory components, rather than mere abnormal sensation. Therefore, integrative understanding of the pain system is necessary for appropriate neuromodulation of chronic trigeminal neuropathy. The possible neuromodulation targets that participate in complex pain processing are as follows: the ventral posterior medial, periaqueductal gray, motor cortex, nucleus accumbens, subthalamic nucleus, globus pallidus internus, anterior cingulate cortex, hypothalamus, sphenopalatine ganglion, and occipital nerve. In conclusion, neuromodulation interventions for trigeminal neuralgia is yet to be elucidated; future advancements in this area are required.
Learn More >CTK 01512-2 toxin is a recombinant peptide of the Phα1β version derived from the venom of the Phoneutria nigriventer spider. It acts as an N-type voltage-gated calcium channel (VGCC) blocker and shows a prolonged effect on preventing and reducing nociception. Herein, CTK 01512-2 was tested on two models of persistent pain, the chronic post-ischemia pain (CPIP) and the paclitaxel-induced peripheral neuropathy, to evaluate its systemic, intrathecal, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia. Glial cell viability was also investigated using the MTT test. The results showed that CTK 01512-2 intrathecal and systemic treatments reduced the mechanical hypersensitivity induced by CPIP, mainly between 1-4 h after its administration. Additionally, intrathecal treatment reduced the CPIP-induced thermal allodynia. In its turn, the intracerebroventricular treatment showed mechanical antihyperalgesic and thermal antiallodynic effects in the paclitaxel-induced peripheral neuropathy. These data reinforce the therapeutic potential of CTK 01512-2 to treat persistent pain conditions and offer a perspective to use the systemic route. Moreover, CTK 01512-2 increased the glial cell viability in the MTT reduction assay, and it may indicate a new approach to managing chronic pain. The results found in this study help to pave new perspectives of pain relief treatments to patients affected by chronic pain.
Learn More >Neuropathic pain often originates from nerve injury or diseases of the somatosensory nervous system. However, its specific pathogenesis remains unclear. The requirement for excitatory synaptic plasticity in pain-related syndromes has been demonstrated. A recent study reported that pentraxin-3 is important in glutamatergic synaptic formation and function. Meanwhile, nectin-1 mediates synaptogenesis in neurological disorders. The present study aimed to evaluate whether pentraxin-3 and nectin-1 modulate spinal nerve damage-related neuropathic pain in male mice. L spinal nerve ligation (SNL) in male mice was performed to induce experimental neuropathic pain. Mechanical allodynia and heat hyperalgesia following SNL were based on paw withdrawal (PW) threshold and PW latency, respectively. Spinal pentraxin-3 levels and nectin-1 expression following SNL were examined. Pentraxin-3 and nectin-1 knockdown models were established by the shRNA method. These models were used with a recombinant pentraxin-3 cell model to investigate the underlying mechanisms of SNL. The SNL operation generated persistent decreases in mechanical PW threshold and thermal PW latency, with subsequent long-lasting elevations in spinal pentraxin-3 and nectin-1 expression levels. Pentraxin-3 knockdown reduced SNL-associated neuropathic pain behaviors as well as nectin-1 amounts in the spinal dorsal horn. Nectin-1 deficiency impaired mechanical allodynia and thermal hyperalgesia following spinal nerve injury. The application of recombinant pentraxin-3 in the spinal cord triggered an acute nociception phenotype and induced spinal overexpression of nectin-1. The intrathecal knockdown of nectin-1 prevented exogenous pentraxin-3-evoked pain hypersensitivity. The findings suggest spinal pentraxin-3 is required for SNL-triggered neuropathic pain via nectin-1 upregulation in male mice.
Learn More >Dupilumab has demonstrated a great reduction on chronic pruritus that is the hallmark of atopic dermatitis (AD). Underscoring relevant pathogenesis similarities emerging from AD, chronic idiopathic pruritus (CIP) and chronic prurigo (CP), several authors suggested the beneficial role of dupilumab in these conditions. The evidence on this subject is limited with no precise data available. In this study, we carried out a systematic literature review in order to evaluate the efficacy of dupilumab on both pruritus and skin manifestations in the two largest retrospective cohorts of patients with CP and CIP and tried to identify potential response predictors. Electronic searches were conducted on 4 databases. Our primary outcome was the improvement in pruritus measured by a reduction in patient's reported numerical rating scale of itch (NRSI) by > 4. Secondary outcomes included: proportion of patients with complete response at the end of treatment, reduction in the number of lesions by the Investigator Global Assessment (IGA), improvement in numerical rating scale of sleep (NRSS), improvement in quality of life measured by the Dermatology Life Quality Index (DLQI), time until patient perceived any improvement (Time-First) and time until patient reported absence of pruritus (Time-Final). Descriptive statistics were calculated for each demographic and clinical variable. Univariate logistic regression analyses were conducted to explore association between response to dupilumab and potential predictive factors. We included 25 articles in the analysis, counting a total of 153 patients. Based on CP patients' cohort (n=132), the mean NRSI at baseline was 8.79 ±0.86 and the NRSI final was 2.32 ±1.27. The mean time to first improvement was 5.18 ±3.13 weeks, while the time to complete improvement of pruritus (Time-final) was 13.6 ±12.0 weeks. Ninety patients out of 109 (83%) noticed improvement in pruritus before 4 weeks of dupilumab therapy. At the end of treatment, 18 patients out of 126 (14%) had a complete remission of pruritus and 110 patients out of 123 (89%) had a reduction of NRSI > 4. The reduction in NRSI was significantly greater in patients improving before 4 weeks of treatment (6.57 ±1.71) compared to patients improving in more than 4 weeks (5.49 ±1.39, p<0.001). Patients with history of AD and those who have been previously treated with cyclosporine or methotrexate had a significantly lower reduction in NRSI (e.g. 6.05 ±1.34 vs 7.08 ±1.90 p<0.01 for non-associated AD patients). Based on CIP patient's cohort (n=21), the mean NRSI at baseline was 8.33 ±0.80 and the NRSI final was 0.95 ±0.59. The mean time to first improvement was 2 ±0 weeks, while the time to complete improvement (Time-final) was 14.6 ±10 weeks. At the end of treatment, 3 patients out of 21 (14%) had a complete remission of pruritus and 100% of patients had a reduction of NRSI > 4. No serious treatment-emergent adverse events were reported. The most common adverse event was mild conjunctivitis (13 cases). We highlight the importance of one early sign of improvement as predictor of the future response to dupilumab: the improvement before 4 weeks of treatment that leads significantly to a greater final reduction in NRSI. Furthermore, patients with the presence or history of atopy appear to be less responsive to dupilumab than non-atopic patients and develop more side effects, in particular conjunctivitis.
Learn More >Understanding chronic pain and disability requires a consideration of the lived experience of the patient. There is limited evaluation of the content validity of patient-reported outcome measures (PROMs) in chronic pain using a comprehensive biopsychosocial view of the patient's experience. To address this gap, this study aimed to evaluate the content validity of PROMs for patients with chronic pain. A literature review was performed to identify PROMs for patients with chronic pain. Concepts from PROMs were linked to the International Classification of Functioning, Disability, and Health (ICF); the ICF Core Set for Chronic Widespread Pain; and the International Classification of Diseases-11 Functioning Properties of Chronic Pain (FP). Concepts were compared with published "attributes'' of chronic pain. 62 PROMs (1336 items total) were identified and linked to 560 unique second-level ICF categories. The greatest number of items across PROMs were represented in the activities and participation category (44% of all total items), followed by body functions (41%), environmental factors (9%), personal factors (5%), and body structures (0.3%). There was a 41% to 78% match with the Core Set for Chronic Widespread Pain and the International Classification of Diseases-11 FP, respectively. 20% of items reflected the pain-experience attributes with the most items reflecting the concept of "control over pain." Content validity analysis suggests chronic widespread pain patient-reported outcome measures poorly address attributes of living with chronic pain that matter most to patients. Future development or refinement should consider a more comprehensive view of the patients' lived experience.
Learn More >Low Back Pain (LBP) is currently the first cause of disability in the world, with a significant socioeconomic burden. Diagnosis and treatment of LBP often involve a multidisciplinary, individualized approach consisting of several outcome measures and imaging data along with emerging technologies. The increased amount of data generated in this process has led to the development of methods related to artificial intelligence (AI), and to computer-aided diagnosis (CAD) in particular, which aim to assist and improve the diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of CAD in the diagnosis and treatment of chronic LBP. A systematic research of PubMed, Scopus, and Web of Science electronic databases was performed. The search strategy was set as the combinations of the following keywords: "Artificial Intelligence", "Machine Learning", "Deep Learning", "Neural Network", "Computer Aided Diagnosis", "Low Back Pain", "Lumbar", "Intervertebral Disc Degeneration", "Spine Surgery", etc. The search returned a total of 1536 articles. After duplication removal and evaluation of the abstracts, 1386 were excluded, whereas 93 papers were excluded after full-text examination, taking the number of eligible articles to 57. The main applications of CAD in LBP included classification and regression. Classification is used to identify or categorize a disease, whereas regression is used to produce a numerical output as a quantitative evaluation of some measure. The best performing systems were developed to diagnose degenerative changes of the spine from imaging data, with average accuracy rates >80%. However, notable outcomes were also reported for CAD tools executing different tasks including analysis of clinical, biomechanical, electrophysiological, and functional imaging data. Further studies are needed to better define the role of CAD in LBP care.
Learn More >Recent neuroimaging studies have revealed important aspects of the underlying pathophysiological mechanisms of migraine suggesting abnormal brain energy metabolism and altered functional connectivity. Proton magnetic resonance spectroscopy (1H-MRS) studies investigated migraine patients in the interictal or ictal state. This first-of-its-kind study aimed to investigate the whole migraine cycle using 1H-MRS and resting-state functional magnetic resonance imaging (fMRI). A migraine patient underwent 1H-MRS and resting-state fMRI for 21 consecutive days, regardless of whether he was in an interictal or ictal state. Metabolite ratios were assessed and compared to the intrinsic connectivity of subcortical brain areas. Probable migraine phase-dependent changes in N-acetyl aspartate (NAA)/total creatine (tCr) and choline (Cho)/tCr levels are found in the left occipital lobe and left basal ganglia. NAA reflects neuronal integrity and Cho cellular membrane turnover. Such abnormalities may increase the susceptibility to excitatory migraine triggers. Functional connectivity between the right hippocampus and right or left pallidum was strongly correlated to the NAA/Cho ratio in the right thalamus, suggesting neurochemical modulation of these brain areas through thalamic connections. To draw statistically significant conclusions a larger cohort is needed.
Learn More >Excessive pelvic floor muscle activity has been suggested as a source of pain in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Our objective was to determine whether men with CP/CPPS have changes in neural drive that impair their ability to relax pelvic floor muscles.
Learn More >This systematic review aimed to investigate variations of reference scores for the Pain Catastrophizing Scale (PCS) between language versions and between countries in patients with chronic primary pain (CPP) or chronic primary pain, not otherwise specified (CPP-NOS).
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