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Pharmaceutical opioid (PO) overdose deaths have increased in many Western countries. There are indications that those dying from a PO overdose differ from those dying from other types of overdoses. These differences might pose a challenge as the majority of current preventive measures are tailored toward those with the characteristics of "conventional" overdose deaths.
Learn More >Painkiller administration lowers pain empathy, but whether this also reduces prosocial behavior is unknown. In this preregistered study, we investigated whether inducing analgesia through a placebo painkiller reduced effortful helping. When given the opportunity to reduce the pain of another person, individuals experiencing placebo analgesia ( = 45 adults from Austria; 21 male, 24 female) made fewer prosocial choices at the lowest helping level and exerted less physical effort when helping, compared with controls whose pain sensitivity was unaltered ( = 45; 21 male, 24 female). Self-reported empathic unpleasantness positively correlated with prosocial choices across the whole sample. While not replicating group differences in empathy, a mediation analysis revealed that the level of unpleasantness to other people's pain fully mediated the effect of placebo analgesia on prosocial choices. Given the importance of prosociality for social cohesion, these findings have broad potential implications both for individuals under the influence of painkillers and for society at large.
Learn More >Cognitive impairments in patients with chronic pain are increasingly attracting interest in scientific research. The consequences of these cognitive impairments on coping with pain, everyday life and the driving ability are rarely included in clinical practice although half of all patients are affected. This article summarizes the current research situation and discusses possibilities of the integration in clinical and therapeutic care.
Learn More >The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs) and, more recently, of Janus kinase inhibitors (JAKi) has had a major impact on the long-term outcomes of chronic inflammatory arthritis (IA). However, the persistence of pain, even in patients with a complete pharmacological control of peripheral inflammation, represents an important clinical challenge in the treatment of IA.
Learn More >Psychiatric comorbidity is common in patients with chronic pain. In peripheral neuropathic pain, particularly anxiety and mood disorders are frequently present and associated with a high level of catastrophizing. Small fiber neuropathy (SFN) is a peripheral neuropathy dominated by pain. This study aimed to investigate the prevalence of, and factors associated with anxiety and depressive symptoms in SFN.
Learn More >Transient Receptor Potential Melastatin 8 (TRPM8) from the melastatin TRP channel subfamily is a non-selective Ca-permeable ion channel with multimodal gating which can be activated by low temperatures and cooling compounds, such as menthol and icilin. Different conditions such as neuropathic pain, cancer, overactive bladder syndrome, migraine, and chronic cough have been linked to the TRPM8 mode of action. Despite the several potent natural and synthetic inhibitors of TRPM8 that have been identified, none of them have been approved for clinical use. The aim of this study was to discover novel blocking TRPM8 agents using automated patch clamp electrophysiology combined with a ligand-based virtual screening based on the SwissSimilarity platform. Among the compounds we have tested, nebivolol and carvedilol exhibited the greatest inhibitory effect, with an IC of 0.97 ± 0.15 µM and 9.1 ± 0.6 µM, respectively. This study therefore provides possible candidates for future drug repurposing and suggests promising lead compounds for further optimization as inhibitors of the TRPM8 ion channel.
Learn More >This study explored a set of psychological and socio-demographic factors in childhood and adulthood associated with migraines assessed at age 42 years. Data were drawn from a large, nationally representative, prospective longitudinal study: the 1970 British Cohort Study (BCS70). In total, 5628 cohort members with data on parental social class at birth, cognitive ability (intelligence), self-esteem and locus of control at age 10 years, psychological distress and educational qualifications at age 34, and current occupation at age 42 years were examined. We assessed whether or not they regularly experienced migraines at age 42 years. Logistic regression analysis showed that childhood migraine, gender and adult psychological distress, as well as childhood locus of control (for females only), were significant and independent predictors of the prevalence of migraine in adulthood. Childhood migraine seemed to have a long-lasting effect on adult migraine, and psychological distress also appeared to detrimentally affect adult migraine over time.
Learn More >Neuropathic pain is a serious health problem, but optimal drug treatments remain lacking. It has been known that the compound NS5806 is a Kv4.3 activator, which increases Kv4.3-mediated K current to reduce neuronal excitability. In this study, we investigated the molecular and cellular mechanisms underlying the analgesic effect of NS5806 in neuropathic pain induced by peripheral nerve injury. Using lumbar (L)5/L6 spinal nerve ligation (SNL) in rats, we found that, without changing the basal nociception, the analgesic effect of NS5806 (220 μg/kg) peaked at 4 hours and lasted for 8 hours after intraperitoneal injection. Multiple doses of NS5806 reduced not only SNL-upregulated proinflammatory mediators in the DRG and spinal cord on day 1 and day 4 after L5/L6 SNL, but also SNL-evoked expansion of DRG macrophages and spinal microglia on day 4. Furthermore, at 10 minutes after L5 SNL, NS5806 pretreatment for 4 hours suppressed SNL-induced phosphorylated extracellular signal-regulated kinase (pERK) in both Kv4.3 and Kv4.3 neurons in the dorsal root ganglion (DRG) and superficial spinal dorsal horn, indicating that the action of NS5806 is not restricted to Kv4.3 neurons. In vitro kinase activity assays revealed that NS5806 weakly inhibited ERK2, MEK1, MEK2, and c-Raf in the ERK pathway. Since NS5806 and the ERK pathway inhibitors have similar antinociceptive characteristics, this study suggests that NS5806 also acts as an ERK pathway inhibitor to attenuate neuropathic pain.
Learn More >Astrocytes, the most abundant type of glial cell, are electrically non-excitable cells that use intracellular calcium (Ca) for functional regulation. Changes in intracellular Ca concentration play important roles in the central nervous system (CNS), as they are involved in the release of gliotransmitters and the control of extracellular ion concentrations, thereby affecting the regulation of neuronal excitability, CNS homeostasis, and behavior. Intracellular calcium mobilization in astrocytes is known to be mediated via inositol 1,4,5-trisphosphate receptors (IPRs), particularly IPR2, and its association with CNS pathogenesis has been widely reported. In addition, the existence of IPR2-independent calcium signaling has recently been postulated; however, the detailed mechanisms and its role in astrocyte functions and CNS pathogenesis are still poorly understood. In this paper, we describe the putative mechanisms underlying IPR1-dependent calcium signaling in astrocytes and its effects on the reactive state, compare this signaling with IPR2-dependent calcium signaling, and discuss its contribution to chronic itch-like behavior.
Learn More >Heart failure (HF) is considered one of the main causes of morbidity and death among chronic diseases worldwide. Patients have increasingly reported chronic pain in long-standing heart failure as a disturbing symptom. Its unknown etiology and mechanism, in addition to its insidious progressive nature, made both the doctor and the patient not notice it until it affects the quality of life (QoL) and general health status. The primary objective of this study is to find the prevalence of pain in chronic heart failure patients and its impact on their QoL. The secondary objective is to determine the predictors of QoL in HF patients.
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