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Specialized pro-resolving mediators (SPMs), including resolvins, protectins, and maresins, are endogenous lipid mediators that are synthesized from omega-3 polyunsaturated fatty acids during the acute phase or resolution phase of inflammation. Synthetic SPMs possess broad safety profiles and exhibit potent actions in resolving inflammation in preclinical models. Accumulating evidence in the past decade has demonstrated powerful analgesia of exogenous SPMs in rodent models of inflammatory, neuropathic, and cancer pain. Furthermore, endogenous SPMs are produced by sham surgery and neuromodulation (e.g., vagus nerve stimulation). SPMs produce their beneficial actions through multiple G protein-coupled receptors, expressed by immune cells, glial cells, and neurons. Notably, loss of SPM receptors impairs the resolution of pain. I also highlight the emerging role of SPMs in the control of itch. Pharmacological targeting of SPMs or SPM receptors has the potential to lead to novel therapeutics for pain and itch as emerging approaches in resolution pharmacology. Expected final online publication date for the , Volume 63 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Learn More >Survey data from the United Stated, the United Kingdom, and the Netherlands indicate peristomal itch is prevalant among ostomy patients. Pruritus has a significant negative impact on health-related quality of life, resulting in discomfort and interrupted sleep. In ostomy patients, peristomal skin scratching also may interfere with adherence of the ostomy pouching system. This article reviews the classification and pathophysiology of itch in the peristomal skin, along with options for its management.
Learn More >Chronic pain and depression are both widely prevalent comorbid medical conditions. While efficient, μ-opioid receptor-based medications are associated with life-threatening side effects, including respiratory depression, dependence, and addiction. The δ-opioid receptor is a promising alternative biological target for chronic pain and depression due to its significantly reduced on-target side effects compared to the μ-opioid receptor. A previous study identified two δ-opioid receptor positive allosteric modulators. Herein, we report the design of five series of compounds targeting previously unexplored regions of the originally described SAR. Analogs were assessed for their ability to potentiate the agonist response of Leu-enkephalin. Of the 30 analogs, compound displayed trends toward enhancing the ERK1/2 phosphorylation signaling compared to cAMP inhibition, while compound exhibited a trend in shifting the signaling bias toward cAMP inhibition. Both and emerged as promising tool compounds toward the design of prospective therapeutics requiring specific downstream signaling attributes.
Learn More >Knee osteoarthritis (OA) is the most common form of OA and a leading cause of disability worldwide. Chronic pain and functional loss secondary to knee OA put patients at risk of developing depression, which can also impair their treatment response. However, no tools exist to assist clinicians in identifying patients at risk. Machine learning (ML) predictive models may offer a solution. We investigated whether ML models could predict the development of depression in patients with knee OA and examined which features are the most predictive.
Learn More >To comprehensively summarize and meta-analyze the concurrence across voxel-based morphometric (VBM) neuroimaging studies of migraine.
Learn More >Chronic pain can be a debilitating condition, leading to profound changes in nearly every aspect of life. However, the reliance on opioids such as oxycodone for pain management is thought to initiate dependence and addiction liability. The neurobiological intersection at which opioids relieve pain and possibly transition to addiction is poorly understood. Using RNA sequencing pathway analysis in rats with complete Freund's adjuvant (CFA)-induced chronic inflammation, we found that the transcriptional signatures in the medial prefrontal cortex (mPFC; a brain region where pain and reward signals integrate) elicited by CFA in combination with oxycodone differed from those elicited by CFA or oxycodone alone. However, the expression of Egr3 was augmented in all animals receiving oxycodone. Furthermore, virus-mediated overexpression of EGR3 in the mPFC increased mechanical pain relief but not the affective aspect of pain in animals receiving oxycodone, whereas pharmacological inhibition of EGR3 via NFAT attenuated mechanical pain relief. Egr3 overexpression also increased the motivation to obtain oxycodone infusions in a progressive ratio test without altering the acquisition or maintenance of oxycodone self-administration. Taken together, these data suggest that EGR3 in the mPFC is at the intersection of nociceptive and addictive-like behaviors.
Learn More >The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review.
Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD-related pain, which suggests that alterations in autonomic tone may contribute to this pain condition.
Learn More >Nationwide perspectives on cannabis have changed dramatically over recent decades. Although cannabis remains illegal at the federal level, medical cannabis (MC) is now legal in most states, and research has continued to show its effectiveness in a variety of medical conditions. However, both perception and acceptance of MC by the general public are evolving and remain poorly understood. Treating patients effectively with these novel therapeutics requires an understanding of the complex interplay of social and legal factors that could affect patient use. This cross-sectional survey study of more than 2500 patients sought to assess current patient perspectives on MC and to investigate factors related to its use that may represent barriers to broader patient use. Most respondents would consider using MC for chronic pain or other medical conditions. Most respondents were aware of the legal status of MC in their state, and 9 of 10 respondents believed that MC should be legal throughout the United States. General public knowledge of the utility of MC is an area needing improvement because older patients were significantly less likely to believe that MC is safe to use or that MC is safer than prescription opioids. As has been reported in previous literature, social stigma and cost appear to remain barriers for patient use of MC. Our findings provide further insight into current patient perspectives on MC, aiding both medical providers and researchers as we continue to provide access to and research MC. [. 20XX;XX(X):xx-xx.].
Learn More >Inadequate pain control after median sternotomy leads to reduced mobilization, increased respiratory complications, and longer hospital stays. Typically, postoperative pain is controlled by opioid analgesics that may have several adverse effects. Parasternal intercostal block (PSB) has emerged as part of a multimodal strategy to control pain after median sternotomy. However, the effectiveness of this intervention on postoperative pain control and analgesic use has not been fully established.
Learn More >Characterize use and efficacy/effectiveness of virtual, augmented, or mixed reality (VR/AR/MR) technology as non-pharmacological therapy for chronic pain. Systematic search of 12 databases to identify empirical studies, of individuals who experience chronic pain or illness involving chronic pain, published between 1990 and 2021. JBI Critical Appraisal Checklists assessed study bias and a narrative synthesis was provided. 46 studies, investigating a total of 1456 participants and including 19 randomized controlled trials (RCT), were reviewed. VR/AR/MR was associated with improved pain-related outcomes in 78% of the RCTs. While most studies showed effects immediately or up to one month post treatment, RCTs are needed to further evaluate VR/AR/MR, establish long-term benefits, and assess accessibility, especially among individuals who experience pain management disparities.
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