Browse by Audience
Fatigue, pain, headache, brain fog, anosmia, ageusia, mood symptoms, and sleep disorders are symptoms commonly experienced by people with post-COVID-19 condition. These symptoms could be considered as manifestations of central sensitization. The aim of this study is to evaluate whether there are indicators of central sensitization by using experimental pain measurements and to determine their association with patient-reported outcome measures (PROMs). A cross-sectional study including 42 patients after COVID-19 infection was conducted. The central sensitization inventory (CSI) was administered as a PROM to evaluate central-sensitization-associated symptoms. Pressure pain thresholds (PPT), temporal summation, and descending nociceptive pain inhibition (CPM) were assessed as experimental pain measurements. The median score on the CSI was 46.5 (Q1-Q3: 33-54). The presence of central-sensitization-associated symptoms was seen in 64.3% of patients based on the CSI (≥40/100 points). A deficient CPM was seen in 12% and 14% of patients when measured at the trapezius and rectus femoris, respectively. A negative correlation between pressure sensitivity on the rectus femoris and the CSI score (r = -0.36, 95%CI -0.13 to -0.65, = 0.007) was observed. Central-sensitization-associated symptoms were present in up to 64.3% of patients post-COVID-19 infection, based on a PROM, i.e., the CSI. A more objective evaluation of nociceptive processing through experimental pain measurements was less suggestive of indicators of central sensitization. Only a small negative correlation between pressure sensitivity and the CSI was observed, thereby pointing towards the discrepancy between the CSI and experimental pain measurements and presumably the complementary need for both to evaluate potential indicators of central sensitization in this population.
Learn More >A wastewater-based epidemiology (WBE) method is presented to estimate analgesic consumption and assess the burden of treated pain in Australian communities. Wastewater influent samples from 60 communities, representing ∼52% of Australia's population, were analyzed to quantify the concentration of analgesics used to treat pain and converted to estimates of the amount of drug consumed per day per 1000 inhabitants using pharmacokinetics and WBE data. Consumption was standardized to the defined daily dose per day per 1000 people. The population burden of pain treatment was classified as mild to moderate pain (for non-opioid analgesics) and strong to severe pain (for opioid analgesics). The mean per capita weighted total DDD of non-opioid analgesics was 0.029 DDD/day/person, and that of opioid-based analgesics was 0.037 DDD/day/person across Australia. A greater burden of pain (mild to moderate or strong to severe pain index) was observed at regional and remote sites. The correlation analysis of pain indices with different socioeconomic descriptors revealed that pain affects populations from high to low socioeconomic groups. Australians spent an estimated US $3.5 (AU $5) per day on analgesics. Our findings suggest that WBE could be an effective surveillance tool for estimating the consumption of analgesics at a population scale and assessing the total treated pain burden in communities.
Learn More >Endometriosis (EM), defined as the presence of endometrial-like tissue with surrounding smooth muscle cells outside the uterus, is a disregarded gynecological disease reported to affect 6-10% of women of reproductive age, with 30-50% of them suffering from chronic pelvic pain and infertility. Since the exact pathogenic mechanisms of EM are still unclear, no curative therapy is available. As pain is an important factor in EM, optimal analgesia should be sought, which to date has been treated primarily with non-steroidal anti-inflammatory drugs (NSAIDs), metamizole or, in extreme cases, opioids. Here, we review the pain therapy options, the mechanisms of pain development in EM, the endogenous opioid system and pain, as well as the opioid receptors and EM-associated pain. We also explore the drug abuse and addiction to opioids and the possible use of NOP receptors in terms of analgesia and improved tolerability as a target for EM-associated pain treatment. Emerging evidence has shown a promising functional profile of bifunctional NOP/MOP partial agonists as safe and nonaddictive analgesics. However, until now, the role of NOP receptors in EM has not been investigated. This review offers a thought which still needs further investigation but may provide potential options for relieving EM-associated pain.
Learn More >Although the painful and disabling features of early diffuse cutaneous systemic sclerosis (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate dose prednisolone in early dcSSc.
Learn More >Cannabinoid type 2 receptor (CB2R) is a G-protein-coupled receptor that, together with Cannabinoid type 1 receptor (CB1R), endogenous cannabinoids and enzymes responsible for their synthesis and degradation, forms the EndoCannabinoid System (ECS). In the last decade, several studies have shown that CB2R is overexpressed in activated central nervous system (CNS) microglia cells, in disorders based on an inflammatory state, such as neurodegenerative diseases, neuropathic pain, and cancer. For this reason, the anti-inflammatory and immune-modulatory potentials of CB2R ligands are emerging as a novel therapeutic approach. The design of selective ligands is however hampered by the high sequence homology of transmembrane domains of CB1R and CB2R. Based on a recent three-arm pharmacophore hypothesis and latest CB2R crystal structures, we designed, synthesized, and evaluated a series of new N-adamantyl-anthranil amide derivatives as CB2R selective ligands. Interestingly, this new class of compounds displayed a high affinity for human CB2R along with an excellent selectivity respect to CB1R. In this respect, compounds exhibiting the best pharmacodynamic profile in terms of CB2R affinity were also evaluated for the functional behavior and molecular docking simulations provided a sound rationale by highlighting the relevance of the arm 1 substitution to prompt CB2R action. Moreover, the modulation of the pro- and anti-inflammatory cytokines production was also investigated to exert the ability of the best compounds to modulate the inflammatory cascade.
Learn More >While systematic reviews have examined medication effectiveness for post-traumatic headache (PTH), they have not assessed tolerability.
Learn More >Chronic low back pain is difficult to treat and despite increased spending on health services, clinical outcomes for people with low back pain have not improved. Innovative, large scale initiatives seem necessary to stem the cost of low back pain. Psychological health contributes to the development and persistence of chronic low back pain and psychological interventions are important in the management of low back pain. Given the contribution of psychological health to low back pain development and management, it raises the question; can we support psychological health in later life by bolstering emotional development in early life, and reduce the burden of this common condition? Positive early life experiences, including those induced by extended paid postnatal leave, could bolster emotional development and support the psychological health necessary to manage low back pain in later life. We present the current state of evidence demonstrating the potential value of increasing support for parent-child relationships in early life to reduce the burden of low back pain in future generations. The current evidence is limited to cross-sectional associations, but strong preclinical data clearly shows the potential negative impacts of maternal separation on rodent pup health that compels consideration in human populations. PERSPECTIVE: The benefits stemming from enhanced child development include stable emotional foundations, possibly improving psychological health and low back pain management in the future. This perspective raises questions for future studies – within the context of low back pain, what ingredients bolster stable psychological health? And are these ingredients influenced by postnatal leave?
Learn More >No validated measure for pain self-efficacy in children and adolescents is currently available in the German language, and existing English versions have limitations. This study used a thorough development process to create the Scale for Pain Self-Efficacy (SPaSE) in both German and English languages. Scale development was based on self-efficacy theory, adapting items from existing self-efficacy measures, and review of patients' perspectives. The final version of the 11-item SPaSE was created with expert discussions and testing of content validity, comprehensibility and construct validity. The validation process consisted of exploratory factor analysis, testing of item characteristics, internal consistency and sensitivity to change in two German samples of children and adolescents with chronic pain (study 1: outpatient sample N=150, inpatient sample N=31). Cross-validation in a US sample (study 2: N=98) confirmed the one-factor structure, the sound psychometric properties and reliability of the SPaSE. Sum scores of the SPaSE were negatively correlated with pain-related disability, pain intensity, passive pain coping strategies and emotional distress, in line with previous research. The valid and reliable SPaSE can be used in clinical practice to monitor pain treatment progress, advances the field of pain self-efficacy research in Germany, and opens the door to comparative research in German and English samples.
Learn More >Administration of cisplatin and other chemotherapy drugs is crucial for treating tumors. However, cisplatin-induced pain hypersensitivity is still a critical clinical issue, and the underlying molecular mechanisms have remained unresolved to date. In this study, we found that repeated cisplatin treatments remarkedly upregulated the P2Y12 expression in the spinal cord. Expression of P2Y12 was predominant in the microglia. Pharmacological inhibition of P2Y12 expression markedly attenuated the cisplatin-induced pain hypersensitivity. Meanwhile, blocking the P2Y12 signal also suppressed cisplatin-induced microglia hyperactivity. Furthermore, the microglia Src family kinase/p38 pathway is required for P2Y12-mediated cisplatin-induced pain hypersensitivity via the proinflammatory cytokine IL-18 production in the spinal cord. Blocking the P2Y12/IL-18 signaling pathway reversed cisplatin-induced pain hypersensitivity, as well as activation of N-methyl-D-aspartate receptor and subsequent Ca-dependent signals. Collectively, our data suggest that microglia P2Y12-SFK-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spinal, and P2Y12 could be a potential target for intervention to prevent chemotherapy-induced pain hypersensitivity. PERSPECTIVE: Our work identified that P2Y12/IL-18 played a critical role in cisplatin-induced pain hypersensitivity. This work suggests that P2Y12/IL-18 signaling may be a useful strategy for the treatment of chemotherapy-induced pain hypersensitivity.
Learn More >We evaluated how pain processing and situational pain catastrophizing differed between two music interventions (Unwind and favorite music) and a control condition (white noise). Healthy adults (n=70) completed quantitative sensory testing (QST) measuring pressure pain threshold (PPTh) and tolerance (PPTol), heat pain threshold (HPTh), offset analgesia (OA), temporal summation of pain (TSP), and conditioned pain modulation (CPM). Participants completed three QST rounds with the presence of white noise (control condition), a relaxing music app (Unwind), and their favorite music, which were presented in a randomized order. The Situational Pain Catastrophizing Scale was completed after each round. Friedman tests and post-hoc Wilcoxon signed-rank tests were used to compare pain processing and catastrophizing across the three conditions. Participants' PPTh, PPTol, and HPTh were significantly higher during the favorite music condition compared to the other two conditions, indicating lower pain sensitivity when listening to favorite music. In contrast, OA was lower in the favorite music condition. Although TSP and CPM were induced by the QST paradigm, these did not differ across the three conditions. Situational pain catastrophizing was also significantly lower during the favorite music condition. Several measures of pain sensitivity and situational pain catastrophizing were lower when listening to favorite music compared to relaxing music or white noise. More research is necessary to determine the mechanism(s) by which music modulates pain processing.
Learn More >