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Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that predominantly affects the axial skeleton and is characterized by inflammatory back pain. While much has been published regarding non-steroidal anti-inflammatory drugs and tumor necrosis factor inhibitors, other classes of medications which leverage alternate molecular mechanisms receive less attention. In this review, we summarize a few of the novel targets in axSpA, review the putative mechanism of action of therapies that focus on these targets, and reference the germane recently completed, ongoing, or proposed randomized controlled clinical trials. The agents addressed include inhibitors of interleukin-23, interleukin-17, janus kinases, granulocyte-macrophage colony-stimulating factor, macrophage migration inhibitory factor, antibodies recognizing T cell receptor beta variable 9 gene positive clones, as well as inhibitors of mitogen-activated protein kinase-activated protein kinase-2.

The purpose of this study was to perform a systematic review of the available literature on morphological and functional brain changes measured by modern neuroimaging techniques in patients suffering from chronic cancer-related pain. A systematic search was conducted in PubMed, Embase, and Web of Science using different keyword combinations. In addition, a hand search was performed on the reference lists and several databases to retrieve supplementary primary studies. Eligible articles were assessed for methodological quality and risk of bias and reviewed by two independent researchers. The search yielded only four studies, three of which used MRI and one PET-CT. None of the studies measured longitudinal morphological (i.e., gray or white matter) changes. All studies investigated functional brain changes and found differences in specific brain regions and networks between patients with chronic cancer-related pain and pain-free cancer patients or healthy volunteers. Some of these alterations were found in brain networks that also show changes in non-cancer populations with chronic pain (e.g., the default mode network and salience network). However, specific findings were inconsistent, and there was substantial variation in imaging methodology, analysis, sample size, and study quality. There is a striking lack of research on morphological brain changes in patients with chronic cancer-related pain. Moreover, only a few studies investigated functional brain changes. In the retrieved studies, there is some evidence that alterations occur in brain networks also involved in other chronic non-cancer pain syndromes. However, the low sample sizes of the studies, finding inconsistencies, and methodological heterogeneity do not allow for robust conclusions.

Utilizing cannabis as a therapeutic option for chronic pain (CP) has increased significantly. However, data regarding the potential immunomodulatory effects of cannabis in CP patients remain scarce. We aimed at exploring the relationship between cannabis use and inflammatory cytokines and chemokines among a cohort of CP patients. Adult patients with a CP diagnosis and medical authorization of cannabis were enrolled. Patients completed validated clinical questionnaires and self-reported the effectiveness of cannabis for symptom management. Patients' blood and cannabis samples were analyzed for the presence of four major cannabinoids, two major cannabinoid metabolites, 29 different cytokines/chemokines, and cortisol. The multivariable linear regression model was used to identify cannabis and patient factors associated with immune markers. Fifty-six patients (48±15 years; 64% females) were included, with dried cannabis (53%) being the most common type of cannabis consumed. Seventy percent of products were considered delta-9-tetrahydrocannabinol (Δ-THC)-dominant. The majority of patients (96%) self-reported effective pain management, and 76% reported a significant decrease in analgesic medication usage (≤0.001). Compared with males, female patients had higher plasma levels of cannabidiol (CBD), cannabidiolic acid, Δ-THC, and 11-hydroxy-Δ-tetrahydrocannabinol but lower concentrations of delta-9-tetrahydrocannabinolic acid and 11-nor-9-carboxy-Δ-tetrahydrocannabinol (THC-COOH). Females had significantly lower eotaxin levels (=0.04) in comparison to male patients. The regression analysis indicated that high cannabis doses were related to increased levels of interleukin (IL)-12p40 (=0.02) and IL-6 (=0.01), whereas female sex was associated with decreased eotaxin (≤0.01) concentrations. Blood CBD levels were associated with lower vascular endothelial growth factor (=0.04) concentrations, and THC-COOH was a factor related to decreased tumor necrosis factor alpha (=0.02) and IL-12p70 (=0.03). This study provides further support for the patient-perceived effectiveness of cannabis in managing CP symptoms and reducing analgesic medication consumption. The results suggest a potential sex difference in metabolizing cannabinoids, and the varying immune marker concentrations may support a possible immunomodulatory effect associated with patient sex and cannabis product type. These preliminary findings provide grounds for further validation using larger, well-designed studies with longer follow-up periods.

Chronic pain prevalence among US adults increased between 2010 and 2019. Yet little is known about trends in the use of prescription opioids and nonpharmacologic alternatives in treating pain.

The risk of opioid addiction among people with chronic pain is elevated in those using opioids to self-medicate physical or emotional pain or distress. The purpose of this study is to test the main effect of distress tolerance (DT) on opioid use disorder (OUD) status in people with chronic pain, and the potential moderating effect of DT in the relationship between known addiction risk factors and the development of OUD.

Pain catastrophizing (PC) is a negative cognitive distortion to actual or anticipated pain. This study aims to investigate the relationship between pain catastrophizing, emotional intelligence, pain intensity, and quality of life (QoL) in cancer patients with chronic pain. Eighty-nine outpatients with chronic pain attending pain clinics and palliative care units were recruited. Participants were men (42.7%) and women (57.3%) with an average age of 56.44 years (SD = 14.82). Self-report psychological measures were completed, including a measure of emotional intelligence, a standard measure of PC, a scale assessing pain intensity, and a scale measuring QoL. The PC scale was found to assess three correlated yet different dimensions of pain catastrophizing (helplessness, magnification, and rumination). Moreover, as expected, patients with PC scale scores ≥ 30 had lower scores in functional QoL dimensions and higher scores in the fatigue, pain, and insomnia symptom dimensions. Regression analyses demonstrated that PC (B = - 0.391, p = 0.004), pain intensity (B = - 1.133, p < 0.001), and education (B = 2.915, p = 0.017) remained the only significant variables related to QoL, when controlling for demographic and clinical confounders. Regarding mediating effects, PC and pain intensity were jointly found to be significant mediators in the relationship between emotional intelligence and QoL. Results are discussed in the context of the clinical implications regarding interventions designed to improve cancer patients' quality of life and offer new insight, understanding, and evaluation targets in the field of pain management.

Psoriasis impacts various aspects of patients' health-related quality of life and is associated with sleep problems. However, research discussing the associations between interleukin-17 blockage therapies and sleep problems in patients with psoriasis is insufficient. We aimed to assess the effectiveness of brodalumab in alleviating sleep problems in real-life patients with plaque psoriasis. This analysis was part of the single-arm, open-label, multicenter, prospective, cohort study, ProLOGUE (study period October 2017-March 2020), which involved Japanese patients with plaque psoriasis. Assessments included correlation of Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R) scores (Sleep Problems Index-II [SPI-II] and MOS Sleep-R subscale scores) with multiple patient-reported outcome scores and the Psoriasis Area and Severity Index (PASI) at baseline. Additionally, change from baseline in MOS Sleep-R scores was assessed at weeks 12 and 48 of brodalumab treatment. Seventy-three patients were enrolled (male 82.2%, median age 54.0 years). At baseline, the SPI-II score correlated with the Patient Health Questionnaire-8 score (Spearman correlation coefficient [ρ] = -0.474) and weakly correlated with the Itch Numeric Rating Scale (NRS; ρ = -0.366), Skin Pain NRS (ρ = -0.275), and all Treatment Satisfaction Questionnaire for Medication-9 domain scores (ρ = 0.270, ρ = 0.303, and ρ = 0.322 for effectiveness, convenience, and global satisfaction, respectively) but did not correlate with the PASI score. The SPI-II score and MOS Sleep-R subscale scores, except the Snoring score (p = 0.0319), did not significantly change from baseline to week 12 of brodalumab treatment. In conclusion, treatment with brodalumab did not improve overall sleep problems in real-life patients with plaque psoriasis, suggesting that sleep problems require attention in daily clinical practice (Japan Registry of Clinical Trials identifier, jRCTs031180037).

Several lipoxygenase enzymes and cyclooxygenase-2 stereoselectively convert the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and n-3 docosapentaenoic acid into numerous oxygenated products. Biosynthetic pathway studies have shown, during the resolution phase of acute inflammation, that distinct families of endogenous products are formed. These products were named specialized pro-resolving mediators, given their specialized functions in the inflammation-resolution circuit, enhancing the return of inflamed and injured tissue to homeostasis. The lipoxins, resolvins, protectins and maresins, together with the sulfido-conjugates of the resolvins, protectins and maresins, constitute the four individual families of these local mediators. When administrated in vivo in a wide range of human disease models, the specialized pro-resolving mediators display potent bioactions. The detailed and individual biosynthetic steps constituting the biochemical pathways, the metabolism, recent reports on structure-function studies and pharmacodynamic data of the protectins, are presented herein. Emphasis is on the structure-function results on the recent members of the sulfido conjugated protectins and further metabolism of protectin D1. Moreover, the members of the individual families of specialized pro-resolving mediators and their biosynthetic precursor are presented. Today 43 specialized pro-resolving mediators possessing pro-resolution and anti-inflammatory bioactions are reported and confirmed, constituting a basis for resolution pharmacology. This emerging biomedical field provides a new approach for drug discovery, that is also discussed.

Patients with persistent and severe dry eye disease (DED) have corneal hypersensitivity, resulting in ocular pain, and diquafosol sodium, a potent P2Y receptor agonist, is commonly used to improve the resultant tear film stability. This study determined the effects of diquafosol instillation on the suppression of trigeminal subnucleus caudalis (Vc) neuronal activity and ocular pain by enhancing tear film stability in the model for chronic DED. The effects of diquafosol on the ocular surface were assessed by the topical application for 28 days, starting from the 14th day since unilateral exorbital gland removal (chronic DED). Loss of tear volume secretion in chronic DED rats was significantly reversed by diquafosol instillation after 28 days, compared with saline treatment. The number of eyeblinks and pERK-IR neurons in the superficial laminae of Vc following hypertonic saline administration to the ocular surface was lower in diquafosol-treated chronic DED rats than in saline-treated rats. The neuronal activity evoked by hypertonic saline and mechanical stimulation along with the spontaneous neuronal activity in the superficial laminae of the Vc were suppressed in diquafosol-treated chronic DED rats. These findings suggest that ocular surface instillation of diquafosol for 28 days attenuates the neuronal hyperactivity in the Vc and the ocular pain that often occurs in chronic DED.