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Protease-activated receptor-2 (PAR2) is involved in inflammatory responses and pain, therefore representing a promising therapeutic target for the treatment of immune-mediated inflammatory diseases. However, as for other GPCRs, PAR2 can activate multiple signaling pathways and those involved in inflammatory responses remain poorly defined. Here, we describe a new selective and potent PAR2 inhibitor (I-287) that shows functional selectivity by acting as a negative allosteric regulator on Gα and Gα activity and their downstream effectors, while having no effect on G signaling and βarrestin2 engagement. Such selective inhibition of only a subset of the pathways engaged by PAR2 was found to be sufficient to block inflammation in vivo. In addition to unraveling the PAR2 signaling pathways involved in the pro-inflammatory response, our study opens the path toward the development of new functionally selective drugs with reduced liabilities that could arise from blocking all the signaling activities controlled by the receptor.
Learn More >The purpose of this study was to enhance the understanding of the process that physical therapists undertake when creating and disseminating exercise programs for older adults with chronic back pain.
Learn More >Post-traumatic headaches are a common sequela of mild traumatic brain injury (concussion). It is unclear whether or how these headaches differ phenotypically from primary headaches.
Learn More >To systematically review the effectiveness of manual therapy on fear-avoidance, kinesiophobia, and pain catastrophizing in patients with chronic musculoskeletal pain.
Learn More >Migraine may be associated with neck impairment and migraine chronicity is related to greater disability. However, whether other subclassifications of migraine, such as migraine with aura, are related to neck impairment is currently unknown. The aim of this study was to assess the musculoskeletal aspects of the neck in patients with migraine with and without aura.
Learn More >Pain (eg, needle injections, injuries, and chronic pain) is highly prevalent in childhood and occurs in social contexts. Nevertheless, broader sociocultural influences on pediatric pain, such as popular media, have not been empirically examined. This study examined how pain is portrayed and gendered in children's popular media. A cross-section of children's media targeted towards 4- to 6-year-old children was selected based on popularity, including 10 movies and the first season of 6 television shows. Pain instances were extracted and coded using 2 established observational coding systems assessing sufferer pain characteristics and observer responses (eg, empathic responses). Findings identified 454 instances of pain across the selected media. Violent pain (ie, intentionally inflicted) and injuries were most commonly represented, whereas everyday, chronic-type, and procedural pains were infrequently portrayed. Pain instances were more commonly experienced by boy characters, who also expressed greater distress; yet, observers were more responsive (eg, expressed greater concern) towards girl characters' pain. Overall, observer responses to pain were infrequent, with observers witnessing but not responding to nearly half of pain instances. Observers who did respond expressed an overall lack of empathy towards sufferers. These findings reveal a very narrow depiction of pain presented in children's popular media, with an overall underrepresentation of pain, numerous maladaptive portrayals of pain, and gender differences in both sufferer and observer responses. This study underscores the need for further research to inform how children's popular media is perceived by parents and children and how media may be transformed and harnessed for effective pain education in childhood.
Learn More >Emotion has a strong modulatory effect on pain perception and spinal nociception. Pleasure inhibits pain and nociception, whereas displeasure facilitates pain and nociception. Dysregulation of this system has been implicated in development and maintenance of chronic pain. The current study sought to examine whether emotional modulation of pain could be altered through the use of transcranial direct current stimulation (tDCS) to enhance (via anodal stimulation) or depress (via cathodal stimulation) cortical excitability in the dorsolateral prefrontal cortex. Thirty-two participants (15 female, 17 male) received anodal, cathodal, and sham tDCS on three separate occasions, followed immediately by testing to examine the impact of pleasant and unpleasant images on pain and nociceptive flexion reflex (NFR) responses to electrocutaneous stimulation. Results indicated that tDCS modulated the effect of image content on NFR, F(2, 2175.06) = 3.20, p = 0.04, with the expected linear slope following anodal stimulation (i.e., pleasant < neutral < unpleasant) but not cathodal stimulation. These findings provide novel evidence that the dorsolateral prefrontal cortex is critical to emotional modulation of spinal nociception. Moreover, the results suggest a physiological basis for a previously identified phenotype associated with risk for chronic pain and thus a potentially new target for chronic pain prevention efforts. PERSPECTIVE: This study demonstrated that reduction of dorsolateral prefrontal cortical excitability by transcranial direct current stimulation attenuates the impact of emotional image viewing on nociceptive reflex activity during painful electrocutaneous stimulation. This result confirms there is cortical involvement in emotional modulation of spinal nociception and opens avenues for future clinical research.
Learn More >BELAVY, D. L., J. Van Oosterwijck, M. Clarkson, E. Dhondt, N. L. Mundell, C. Miller and P. J. Owen. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2020. Exercise training is capable of reducing pain in chronic pain syndromes, yet its mechanisms are less well established. One mechanism may be via the impact of exercise on increasing a person's pain threshold. Here we show, via meta-analysis of fifteen exercise training studies in pain syndromes that exercise training leads to increased pressure pain thresholds (low to moderate quality evidence). We also find low to moderate quality evidence exists that exercise training was more effective than non-exercise interventions, such as pain education, massage and stress management for improving pain sensitivity. Further, the effect of exercise was greater locally at the site of pain and less so at remote regions. These finding suggest that adaptations in central inhibition occur over time with exercise training and, more widely, add to the mechanistic understanding of how effective interventions can improve pain in chronic pain syndromes.
Learn More >Pain after breast cancer surgery remains largely unexplained and inconsistently quantified. This study aims to describe the perioperative pain patterns in patients with breast cancer, up to two years after surgery.
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