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A pharmacological approach to pain control after cesarean delivery is often insufficient on its own. Acupuncture is a promising method for mitigating postoperative pain and reducing postoperative opioid requirements.
Learn More >Translational research has changed the understanding of atopic dermatitis (AD) pathogenesis beyond the basic mechanisms of immunology. The study in patients of rational therapies based on targeted therapies (biologicals) provides valuable information from the patient and provides lessons of clinical immunology on clinically relevant mechanism of AD pathogenesis. AD features such as skin barrier defect, skin dysbiosis, and pruritus share a common abnormal adaptive immune response process. Skin-homing CLA+CD4+ memory T-cells produce IL-4, IL-13, and IL-31 which are key mediators in AD pathogenesis. Lessons learned from AD show that translational immunology allows generating rational therapies for AD and learning its immunopathogenesis in the patient.
Learn More >Musculoskeletal pain is a global health concern and work-related psychosocial stress might be a potential contributing factor. This cross-sectional study investigates whether job stress is associated with chronic and widespread musculoskeletal pain in 2,051 Brazilian active civil servants included in the ELSA-Brasil MSK cohort. Job stress was assessed using the Effort-Reward Imbalance (ERI) questionnaire. Associations between ERI domains, categorized into tertiles, and chronic musculoskeletal pain (CMP) at any site and per number of affected sites (0, 1-2, ≥3-multisite pain) and body regions (0, 1-2, 3-generalized pain), were investigated using binary and multinomial logistic regression, adjusted for sociodemographic, occupational and health covariates. The prevalence of CMP at any site, multisite and generalized was 52.9%, 18.2% and 9.5%, respectively. Following adjustments, the lower the reward and the greater the overcommitment, the higher the odds of CMP at any site. The ERI domains were more strongly associated with multisite and generalized CMP than with CMP at any site. Multisite CMP was associated with lower reward, and with greater effort, overcommitment, and effort-reward imbalance ratio. CMP according to body regions, especially generalized pain, was also associated with ERI domains effort (OR=2.06; 95%CI=1.33-3.21), overcommitment (OR=3.44; 95%CI=2.20-5.39), and effort-reward imbalance ratio (OR= 2.06; 95%CI=1.30-3.27). Results reveal an association between job stress not only with CMP at any site, but notably with the pain spread to other body sites/regions. Our findings suggest that lowering stress at work and discouraging overcommitment may help reduce the CMP burden including reduction of CMP spread from one sites/regions of the body to another.
Learn More >Tapentadol is a centrally acting analgesic with a dual mechanism of action. It acts as an agonist at the µ receptor and inhibitor of noradrenaline reuptake. Clinical trials suggest similar analgesic efficacy of tapentadol, oxycodone, and morphine in acute and chronic pain. Given the limited information about the molecular actions of tapentadol at the µ receptor, we investigated the intrinsic efficacy of tapentadol and compared it with other opioids. β-chlornaltrexamine (β-CNA, 100 nM, 20 min) was used to deplete spare receptors in AtT20 cells stably transfected with human µ receptor wild-type (WT). Opioid-mediated changes in membrane potential were measured in real-time using a membrane potential-sensitive fluorescent dye. Using Black and Leff's operational model, intrinsic efficacy relative to DAMGO was calculated for each opioid. Tapentadol (0.05 ± 0.01) activated the GIRK channel with lesser intrinsic efficacy than morphine (0.17 ± 0.02) and oxycodone (0.16 ± 0.02). We further assessed the signaling of tapentadol in the common µ receptor variants (N40D and A6V) which are associated with altered receptor signaling. We found no difference in the response of tapentadol between these receptor variants.
Learn More >As the nervous system develops, nerve fibers from the brain form descending tracts that regulate the execution of motor behavior within the spinal cord, incoming sensory signals, and capacity to change (plasticity). How these fibers affect function depends upon the transmitter released, the receptor system engaged, and the pattern of neural innervation. The current review focuses upon the neurotransmitter serotonin (5-HT) and its capacity to dampen (inhibit) neural excitation. A brief review of key anatomical details, receptor types, and pharmacology is provided. The paper then considers how damage to descending serotonergic fibers contributes to pathophysiology after spinal cord injury (SCI). The loss of serotonergic fibers removes an inhibitory brake that enables plasticity and neural excitation. In this state, noxious stimulation can induce a form of over-excitation that sensitizes pain (nociceptive) circuits, a modification that can contribute to the development of chronic pain. Over time, the loss of serotonergic fibers allows prolonged motor drive (spasticity) to develop and removes a regulatory brake on autonomic function, which enables bouts of unregulated sympathetic activity (autonomic dysreflexia). Recent research has shown that the loss of descending serotonergic activity is accompanied by a shift in how the neurotransmitter GABA affects neural activity, reducing its inhibitory effect. Treatments that target the loss of inhibition could have therapeutic benefit.
Learn More >Small nerve fibres are important when studying diabetic peripheral neuropathy (DPN) as they could be first affected. However, assessing their integrity and function adequately remains a major challenge. The aim of this study was to investigate the association between different degrees of DPN, the presence of neuropathic pain (NP), and the intensity of the axon-reflex flare response provoked by epidermal histamine.
Learn More >The King Baboon spider, , is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from , but the molecular basis by which the venom induces pain is unknown. Proteotranscriptomic analysis of venom uncovered a cysteine-rich peptide, δ/κ-theraphotoxin-Pm1a (δ/κ-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic δ/κ-TRTX-Pm1a (sPm1a) induced hyperexcitability by enhancing tetrodotoxin-resistant sodium currents, impairing repolarization and lowering the threshold of action potential firing, consistent with the severe pain associated with envenomation. The molecular mechanism of nociceptor sensitization by sPm1a involves multimodal actions over several ion channel targets, including Na1.8, K2.1, and tetrodotoxin-sensitive Na channels. The promiscuous targeting of peptides like δ/κ-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms.
Learn More >The first human applications of ultrasound in medicine date back to 1939, when Reimar Pohlmann (Berlin, Germany) published data on therapy of neuralgia with ultrasound […].
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