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Human pain is a salient stimulus composed of two main components: a sensorysomatic component, carrying peripheral nociceptive sensation via the spino-thalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain, and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the central nervous system's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spino-thalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intra-cranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway, or indirectly influenced by interfering with the ascending spino-thalamic tract.

To investigate whether the delay between onset of neurological signs and spinal cord decompression affects the time to recovery in non-ambulatory paraparetic/paraplegic dogs with deep pain perception affected by thoracolumbar intervertebral disc extrusion.

Breast disorders (BD) during pregnancy and postpartum cause anxiety and reduce women's quality of life. The study examined BD risk factors during pregnancy and six months after delivery.

mRNA COVID-19 vaccination was initiated worldwide in late 2020, and its efficacy has been well reported. However, studies about vaccine-related side effects are sparse. A total of 262 health care workers who received mRNA COVID-19 vaccine BNT162b2 were recruited, and their vaccine-related side effects were investigated. Impact of sex and age on the side effects was statistically analyzed. A higher number of vaccine-related side effects among females versus males was identified (median 3 versus 2,  < 0.05, after the first dose, and 5 versus 2.5,  < 0.01, after the second dose). General fatigue, headache, chills, and fever were the culprit adverse symptoms. In multivariate analysis, females had an increasing number of side effects after receiving their first (B = 0.7; 95% confidence interval [CI], 0.2 to 1.2) and second (B = 1.5; 95% CI, 0.7 to 2.2) vaccine doses compared to that of males. In age analysis, the older group (≥60 years old) had a lower number of side effects than the younger group (B = -0.5 with a 95% CI of -1.1 to -0.02 after the first vaccine dose, and B = -2.1 with a 95% CI of -2.9 to -1.2 after the second vaccine dose). Additionally, prolonged time to recovery was found among females ( = 0.003 after the first dose;  = 0.008 after the second dose). Specifically, symptoms of general fatigue, headache, itching, swelling at the injection site, and dizziness were the culprit symptoms affecting recovery time. Several cutaneous and membranous symptoms, including "COVID arm," were identified among females. These results highlight the impact of sex and age on side effects from mRNA COVID-19 vaccine and will aid in creating a safer vaccine. We demonstrate sex- and age-related impact on mRNA COVID-19 vaccine-related side effects, with a higher number and frequency of side effects and prolonged time to recovery in females compared to males and negative correlation between age and vaccine-related side effects. Identification of unique age- and sex-specific adverse symptoms will provide the opportunity to better understand the nature of sex- and age-associated immunological differences and develop safer and more efficacious vaccines.

Non-specific low back pain (LBP) is a major global disease burden and childhood adversity predisposes to its development. The mechanisms are largely unknown. Here, we investigated if adversity in young rats augments mechanical hyperalgesia and how spinal cord microglia contribute to this. Adolescent rats underwent restraint stress, control animals were handled. In adulthood, all rats received two intramuscular injections of NGF/saline or both into the lumbar multifidus muscle. Stress induced in rats at adolescence lowered low back pressure pain threshold (PPT; p = 0.0001) and paw withdrawal threshold (PWT; p = 0.0007). The lowered muscle PPT persisted throughout adulthood (p = 0.012). A subsequent NGF in adulthood lowered only PPT (d = 0.87). Immunohistochemistry revealed changes in microglia morphology: stress followed by NGF induced a significant increase in ameboid state (p < 0.05). Repeated NGF injections without stress showed significantly increased cell size in surveilling and bushy states (p < 0.05). Thus, stress in adolescence induced persistent muscle hyperalgesia that can be enhanced by a mild-nociceptive input. The accompanying morphological changes in microglia differ between priming by adolescent stress and by nociceptive inputs. This novel rodent model shows that adolescent stress is a risk factor for the development of LBP in adulthood and that morphological changes in microglia are signs of spinal mechanisms involved.

Pain and fear associated with needle procedures have been found to be more common among children and adolescents treated for type 1 diabetes (T1D) than among others in their age group. Furthermore, high glycated haemoglobin (HbA1c) values are associated with needle-related fear.

Axial involvement in patients with psoriatic arthritis (PsA) is a common subset of this condition, but a unanimous definition has yet to be established. It has been defined by using different criteria, ranging from the presence of at least unilateral grade 2 sacroiliitis to those used for ankylosing spondylitis (AS), or simply the presence of inflammatory low back pain (IBP). Our aim was to identify and evaluate the efficacy of therapeutic interventions for treatment of axial disease in PsA.

Much of the current research on treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients living with psoriatic arthritis (PsA) predates the approval and uptake of IL (interleukin)-17A inhibitors. To compare real-world treatment patterns and use of adjunctive pain and antiinflammatory medications between patients with PsA initiating the IL-17A inhibitors, ixekizumab and secukinumab, in a US-managed care population. We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/anti-inflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests. In total, 407 patients were identified in the ixekizumab cohort (mean age 51.6 years; 54% female) and 1,508 patients were identified in the secukinumab cohort (mean age 50.1 years; 59% female). Prior to weighting, presence of a psoriasis diagnosis code (ixekizumab: 60% vs secukinumab: 45%; standardized difference [std diff] = -0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = -0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; = 0.411) and switching (25% vs 20%; = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; = 0.187). Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA. Ms Pizzicato, Ms Ketkar, and Dr Grabner are employees of HealthCore, Inc, which received funding from Eli Lilly and Company for the conduct of the study on which this manuscript is based. Ms Pepe was an employee of HealthCore, Inc., during the time the study was conducted. Dr Grabner is a shareholder of Elevance Health (legacy Anthem, Inc.). Dr Vadhariya, Dr Birt, and Ms Bolce are employees of Eli Lilly and Company, the manufacturer of ixekizumab (Taltz). Dr Birt and Ms Bolce are shareholders of Eli Lilly and Company. Dr Walsh is a paid consultant to Eli Lilly and Company and Novartis, the manufacturers of ixekizumab (Taltz) and secukinumab (Cosentyx), respectively. Additionally, Dr Walsh is a paid consultant for Pfizer, Janssen, AbbVie, and UCB and has contracts with Pfizer, AbbVie, and Merck.

Chronic nonspecific low back pain (CNSLBP) is a complex and multifaceted problem. The following Perspective Piece tries to help make sense of this complexity by describing a model for the development and maintenance of persistent low back pain that integrates modifiable factors across the biopsychosocial spectrum. The Fit-for-Purpose model (FFPM) posits the view that chronic nonspecific low back pain represents a state in which the person in pain holds strong and relatively intransient internal models of an immutably damaged, fragile, and unhealthy back, and information that supports these models is more available and trustworthy than information that counters them. This Perspective proposes a corresponding treatment framework for persistent pain that aims to shift internal models of a fragile, damaged, unhealthy, and unchangeable self toward the formulation of the back as healthy, strong, adaptable and fit-for-purpose and to provide the system with precise and trustworthy evidence that supports this supposition while minimizing information that works against it.