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Background and aims Endometriosis is a gynecologic recurring persistent condition affecting from 8% to 15% of premenopausal women worldwide. About 80% of women with endometriosis have at least one form of chronic pain – a multidimensional experience influenced by a number of psychosocial factors, including pain-related beliefs. The Survey of Pain Attitudes is the most commonly used measure of pain-related beliefs. This study aims to evaluate the psychometric properties of a Portuguese version of a brief version of the SOPA (the SOPA-35) in a sample of Portuguese women with Endometriosis. Methods A sample of 199 Portuguese women with Endometriosis provided demographic and pain history information, and completed a Portuguese version of the SOPA-35 and measures of pain intensity, disability, and psychological function. Analyses were performed to evaluate the factor structure of the Portuguese SOPA-35 items as well as the internal consistency, composite reliability, convergent validity, and concurrent validity of the scale scores. Results Confirmatory factor analysis supported a six-factor solution for a 19-item version of the Portuguese version of the Survey of Pain Attitudes (SOPA-19-P). The six scales evidenced marginal to good reliability (Cronbach's alphas: between 0.60 and 0.84; composite reliability: between 0.61 and 0.84). Four scales evidenced acceptable to good convergent validity (AVE: between 0.51 and 0.63). The findings also supported the concurrent validity of the SOPA-19-P. Conclusions The results support the use of the Portuguese SOPA-19-P for research and clinical purposes with Portuguese women in chronic pain due to endometriosis. Future research is warranted to further develop a European Portuguese version of SOPA. Implications The findings provide psychometric information about the SOPA-19-P. The results are helpful to researchers wishing to study the role of pain-related beliefs and their association with adjustment and treatment outcomes in women with chronic pain due to endometriosis.
Learn More >Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system that can lead to severe physical, cognitive, and neurological deficits that often manifest in young adults. Central neuropathic pain is a common presenting symptom, often prompting patients to seek treatment with opioids, NSAIDS, antiepileptics, and antidepressants despite minimal effectiveness and alarming side-effect profiles. Additionally, spasticity occurs in more than 80% of MS patients and is an important consideration for further study in treatment.
Learn More >Mechanical sensitization is one of the most difficult clinical pain problems to treat. However, the molecular and genetic bases of mechanical nociception are unclear. Here we develop a model of mechanical nociception to investigate the ion channels and signaling pathways that regulate mechanical nociception. We fabricated Von Frey filaments that span the sub-threshold to high noxious range for larvae. Utilizing these, we discovered that pressure (force/area) rather than force per se is the main determinant of aversive rolling responses to noxious mechanical stimuli. We demonstrated that the RTK PDGF/VEGF receptor (Pvr) and its ligands (Pvfs 2 and 3) are required for mechanical nociception and normal dendritic branching. Pvr is expressed and functions in class IV sensory neurons, while Pvf2 and Pvf3 are produced by multiple tissues. Constitutive overexpression of Pvr and its ligands or inducible overexpression of Pvr led to mechanical hypersensitivity that could be partially separated from morphological effects. Genetic analyses revealed that the Piezo and Pain ion channels are required for mechanical hypersensitivity observed upon ectopic activation of Pvr signaling. Platelet-derived growth factor (PDGF), but not vascular endothelial growth factor (VEGF) peptides caused mechanical hypersensitivity in rats. Pharmacological inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) signaling attenuated mechanical nociception in rats, suggesting a conserved role for PDGF and VEGFR-2 signaling in regulating mechanical nociception. VEGFR2 inhibition also attenuated morphine analgesic tolerance in rats. Our results reveal that a conserved RTK signaling pathway regulates baseline mechanical nociception in flies and rats.Hypersensitivity to touch is poorly understood and extremely difficult to treat. Using a refined model of mechanical nociception, we discovered a conserved VEGF-related receptor tyrosine kinase signaling pathway that regulates mechanical nociception in flies. Importantly, pharmacological inhibition of VEGFR-2 signaling in rats causes analgesia and blocks opioid tolerance. We have thus established a robust, genetically tractable system for the rapid identification and functional analysis of conserved genes underlying mechanical pain sensitivity.
Learn More >Cortical spreading depression (CSD) is a wave of neuronal depolarization thought to underly migraine aura. Calcitonin gene-related peptide (CGRP) is a potent vasodilator involved in migraine pathophysiology. Evidence for functional connectivity between CSD and CGRP has triggered scientific interest in the possibility that CGRP antagonism may disrupt vascular responses to CSD, and the ensuing plasma protein extravasation (PPE). Using imaging tools that allow us to generate continuous, live, high-resolution views of spatial and temporal changes that affect arteries and veins in the dura and pia, we determined the extent to which CGRP contributes to the induction of arterial dilatation or PPE by CSD in female rats, and how these events are affected by the anti-CGRP monoclonal antibody (anti-CGRP-mAb) fremanezumab. We found that the CSD-induced brief dilatation and prolonged constriction of pial arteries, prolonged dilatation of dural arteries and PPE are all unaffected by fremanezumab, whereas the brief constriction and prolonged dilatation of pial veins are. In comparison, whereas CGRP infusion gave rise to the expected dilatation of dural arteries, which was effectively blocked by fremanezumab, it did not induce dilatation in pial arteries, pial veins, or dural veins. It also failed to induce PPE. Regardless of whether the nociceptors become active before or after the induction of arterial dilatation or PPE by CSD, fremanezumab's inability to prevent them suggests that these events are not mediated by CGRP; a conclusion with important implications for our understanding of anti-CGRP-mAbs' mechanism of action in migraine prevention.The current study identifies fundamental differences between two commonly used models of migraine, CSD induction and systemic CGRP infusion. It raises the possibility that conclusions drawn from one model may not be true or relevant to the other. It sharpens the need to accept the view that to migraine pathophysiology and that it is unlikely that one theory will explain all types of migraine headache or the mechanisms of action of drugs that prevent it. Regarding the latter, it is concluded that not all vascular responses in the meninges are born alike and consequently, that drugs that prevent vascular dilatation through different molecular pathways may have different therapeutic outcomes in different types of migraine.
Learn More >This study aimed to investigate cohort effects in selected opioids use and determine whether cohort differences were associated with changes in risk factors for use over time.
Learn More >To study the efficacy and safety of lasmiditan for acute treatment of migraine in patients using migraine preventive medications.
Learn More >Small-surface-area electrodes have successfully been used to preferentially activate cutaneous nociceptors, unlike conventional large area-electrodes, which preferentially activate large non-nociceptor fibers. Assessments of the strength-duration relationship, threshold electrotonus, and slowly increasing pulse forms have displayed different perception thresholds between large and small surface electrodes, which may indicate different excitability properties of the activated cutaneous nerves. In this study, the origin of the differences in perception thresholds between the two electrodes was investigated. It was hypothesized that different perception thresholds could be explained by the varying distributions of voltage-gated ion channels and by morphological differences between peripheral nerve endings of small and large fibers. A two-part computational model was developed to study activation of peripheral nerve fibers by different cutaneous electrodes. The first part of the model was a finite-element model, which calculated the extracellular field delivered by the cutaneous electrodes. The second part of the model was a detailed multicompartment model of an Aδ-axon as well as an Aβ-axon. The axon models included a wide range of voltage-gated ion channels: Na, Na, Na, K, K, K, and HCN channel. The computational model reproduced the experimentally assessed perception thresholds for the three protocols, the strength-duration relationship, the threshold electrotonus, and the slowly increasing pulse forms. The results support the hypothesis that voltage-gated ion channel distributions and morphology differences between small and large fibers were sufficient to explain the difference in perception thresholds between the two electrodes. In conclusion, assessments of perception thresholds using the three protocols may be an indirect measurement of the membrane excitability, and computational models may have the possibility to link voltage-gated ion channel activation to perception threshold measurements.
Learn More >To estimate the prevalence of cluster headache in working-aged people, compare sickness absence rates and disability pension in cluster headache patients to rates in a matched comparison group, and explore associations of sociodemographic factors with such rates.
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