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Atopic dermatitis is associated with substantial patient and caregiver burden. Currently available treatments for atopic dermatitis are inadequate or contraindicated for some patients. Abrocitinib (PF-04965842) is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of atopic dermatitis.
Learn More >We recently reported that swelling resulting from 2,4,6-trinitrochlorobenzene (TNCB) challenge might be associated with recruitment of neutrophils. However, it is not known whether neutrophil recruitment is affected by scratching at inflamed sites or not. Therefore, the effects of an Elizabethan collar on the TNCB-induced upregulation of ELR-positive chemokines (CXCL1, CXCL2, and CXCL5) and neutrophil recruitment were investigated. Mice were sensitized by the application of TNCB on abdominal skin. Then, the mice were challenged three times with TNCB to auricle of the ear. To prevent scratching at inflamed sites, an Elizabethan collar was placed on the mice from just before the first challenge until the end of the experiment. The effects of the Elizabethan collar on the TNCB-induced upregulation of CXCLs chemokines and recruitment of neutrophil were investigated. The increase of ear swelling by TNCB challenge was inhibited by the Elizabethan collar. TNCB-challenge-induced upregulation of TNF-α, IL-1β, IL-6, ELR chemokines, MPO, and ELA2 was also attenuated by the Elizabethan collar. The gene expression of CXCL1, CXCL2, and CXCL5 human homolog IL-8 was enhanced by TNF-α and IL-1β in human dermal fibroblasts and epidermal keratinocytes. We here suggest that scratching the site of inflammation leads to neutrophil accumulation mediated by TNF-α and IL-1β/ELR chemokines in TNCB-challenge-induced contact dermatitis in mice.
Learn More >Positive and negative expectancies drive behavioral and neurobiological placebo and nocebo effects which in turn can have profound effects on patient improvement or worsening. However, expectations of events and outcomes are often not met in daily life and clinical practice. It is currently unknown how this affects placebo and nocebo effects. We have demonstrated that the violation of expectancies, such as when a discrepancy between what is expected and what is actually presented, reduces both placebo and nocebo effects while causing an extinction of placebo effects. The reduction of placebo and nocebo effects was paralleled by an activation of the left inferior parietal cortex, a brain region that redirects attention when discrepancies between sensory and cognitive events occur. Our findings highlight the importance of expectancy violation in shaping placebo and nocebo effects and open up new avenues for managing positive and negative expectations in clinical trials and practices. This article is protected by copyright. All rights reserved.
Learn More >Due to the current absence of a standardized guide for activity pacing, the concept of pacing is interpreted in various ways by healthcare professionals, patients and researchers. Consequently, the effects of pacing across different conditions are unclear. The present study aimed to undertake the second stage in the development of an activity pacing framework for chronic pain/fatigue.
Learn More >We have previously reported that the microtubule-associated collapsin response mediator protein 2 (CRMP2) is necessary for the expression of chronic pain. CRMP2 achieves this control of nociceptive signaling by virtue of its ability to regulate voltage-gated calcium and sodium channels. To date, however, no drugs exist that target CRMP2. Recently, the small molecule edonerpic maleate (1 -{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), a candidate therapeutic for Alzheimer's disease was reported to be a novel CRMP2 binding compound with the potential to decrease its phosphorylation level in cortical tissues in vivo. Here we sought to determine the mechanism of action of edonerpic maleate and test its possible effect in a rodent model of chronic pain. We observed: (i) no binding between human CRMP2 and edonerpic maleate; (ii) edonerpic maleate had no effect on CRMP2 expression and phosphorylation in dorsal root ganglion (DRG) neurons; (iii) edonerpic maleate-decreased calcium but increased sodium current density in DRG neurons; and (iv) edonerpic maleate was ineffective in reversing post-surgical allodynia in male and female mice. Thus, while CRMP2 inhibiting compounds remain a viable strategy for developing new mechanism-based pain inhibitors, edonerpic maleate is an unlikely candidate.
Learn More >Neurobiological mechanisms can be involved in early programming of pain sensitization. We aimed to investigate the association between early-life pain experience and pre-adolescence spinal pain. We conducted a study of 29,861 pre-adolescents (age 11-14) from the Danish National Birth Cohort. As indicators of early-life pain, we used infantile colic and recurrent otitis media, reported by mothers when their children were 6 and 18 months. Self-reported spinal pain (neck, middle back, and/or low back pain) was obtained in the 11-year follow-up, classified according to severity. Associations between early-life pain and spinal pain in pre-adolescents were estimated using multinomial logistic regression models. To account for sample selection, inverse probability weighting was applied. Children experiencing pain in early life were more likely to report severe spinal pain in pre-adolescence. The association appeared stronger with exposure to two pain exposures (relative risk ratio, 1.31; 95% CI, 1.02-1.68) rather than one (relative risk ratio, 1.14; 95% CI, 1.05-1.24). We observed similar results when using headache and abdominal pain as outcome measures, underpinning a potential neurobiological or psychosocial link in programming of pain sensitization.Conclusion: Experience of early-life pain is seemingly associated with spinal pain in pre-adolescence. The study highlights that early-life painful experiences can influence programming future pain responses. What is Known: • Spinal pain in pre-adolescents is common, causes marked discomfort and impairment in everyday life, and may be an important predictor of spinal pain later in life. • Neurobiological mechanisms have been suggested as involved in early programming of pain sensitization. What is New: • Pain exposure in early postnatal life in terms of infantile colic and recurrent otitis media is associated with spinal pain in pre-adolescence; thus, experience of such painful conditions in the early postnatal period may seemingly influence programming of future pain sensation.
Learn More >Exercise therapy (ET) is advocated as a treatment for chronic nonspecific low back pain (CNSLBP). However, therapy effect sizes remain low. In other chronic disorders, training at higher intensity has resulted in greater improvements on both general health related and disease specific outcomes compared to lower intensity ET. Possibly, high intensity training also improves effect sizes in CNSLBP.
Learn More >Endometriosis impacts the physical, psychological and quality of life domains of women. Despite the medical and/or surgical management of endometriosis, the presence of persistent pelvic pain and psychological distress often continues, suggesting a role for psychological interventions in treatment planning. The present study aimed to conduct the first systematic review, with narrative data synthesis, on psychological interventions for endometriosis-related symptoms. The study also aimed to determine the effectiveness of current interventions in resolving psychological and pain-related loss of function associated with endometriosis and to identify gaps in the literature requiring further research. A total of 15,816 studies were retrieved through database searching and handsearching, with two researchers identifying 11 full-text studies that met inclusion criteria. Three studies of 'moderate' quality were identified, although the overall quality of studies was found to be 'weak', with a 'high' risk of bias. The findings regarding the effectiveness of psychological interventions for endometriosis-related symptoms remain inconclusive. Further research into psychological interventions for women with endometriosis that employ evidence-based protocols with high intervention integrity is recommended.
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