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Pain has sensory and affective components. Unlike traditional, reflex-based pain assays, operant pain assays can produce more clinically relevant results by addressing the cognitive and motivational aspects of pain in rodents. This paper presents a protocol for assessing mechanical hypersensitivity following chronic constriction injury of the infraorbital nerves (CCI-ION) in rats using an orofacial operant pain system. Before CCI-ION surgery, rats were trained in an orofacial pain assessment device (OPAD) to drink sweetened condensed milk while making facial contact with the metal spiked bars and lick-tube. In this assay, rats can choose between receiving milk as a positive reinforcer or escaping an aversive mechanical stimulus that is produced by a vertical row of small pyramid-shaped spikes on each side of the reward access hole. Following 2 weeks of training in the OPAD and before the CCI-ION surgery, baseline mechanical sensitivity data were recorded for 5 days for each rat during a 10 min testing session. During a session, the operant system automatically records the number of reward bottle activations (licks) and facial contacts, contact duration, and latency to the first lick, among other measures. Following baseline measurements, rats underwent either CCI-ION or sham surgery. In this protocol, mechanical hypersensitivity was quantified by measuring the number of licks, latency to the first lick, the number of contacts, and the ratio of licks to facial contacts (L/F). The data showed that CCI-ION resulted in a significant decrease in the number of licks and the L/F ratio and an increase in the latency to the first lick, indicating mechanical hypersensitivity. These data support the use of operant-based pain assays to assess mechanical pain sensitivity in preclinical pain research.
Learn More >Cannabinoid Receptor 2 (CB2) is a G protein-coupled receptor (GPCR) with considerable, though as yet unrealised, therapeutic potential. Promising preclinical data supports the applicability of CB2 activation in autoimmune and inflammatory diseases, pain, neurodegeneration, and osteoporosis. A diverse pharmacopoeia of cannabinoid ligands is available, which has led to considerable advancements in the understanding of CB2 function and extensive preclinical evaluation. However, until recently, most CB2 ligands were highly lipophilic and as such not optimal for clinical application due to unfavourable physicochemical properties. A number of strategies have been applied to develop CB2 ligands to achieve closer to 'drug-like' properties and a few such compounds have now undergone clinical trial. We review the current state of CB2 ligand development and progress in optimising physicochemical properties, understanding advanced molecular pharmacology such as functional selectivity, and clinical evaluation of CB2-targeting compounds.
Learn More >Lornoxicam (LOR), a BCS Ⅱ nonsteroidal anti-inflammatory drug, has been clinically utilized for moderate to severe acute pain management. However, it has poor water solubility and insufficient tabletability, leading to erratic absorption and challenge in tablet processability. This study reported a novel solid state of LOR (i.e., LOR sodium chelate monohydrate, LOR-Na·HO) with significantly improved solubility, dissolution rate and tabletability. The prepared chelate (CCDC No.: 2125157) contains LOR, Na, and HO in a molar ratio of 1:1:1, where Na ions bridged with O(5) of amide group, and N(2) of pyridine group on LOR, as well as O(4) on HO through coordination bonds. LOR-Na·HO displayed a superior dissolution rate (5∼465 folds) than commercial LOR due to its increased wettability (contact angle: 74.5° vs 85.6°) and lower solvation free energy (∼2-fold). In addition, the significant improvement in tabletability was caused by high plasticity and deformability, which was attributed to its special interlayer gliding with weak bonding interactions across layers but strong coordination bonding interactions within layers. The novel LOR-Na·HO with significantly enhanced pharmaceutical performance offers a promising strategy for further product development.
Learn More >Previous studies revealed inconsistent results regarding association between migraine and cognitive impairment. In addition, previous studies found inconsistent results regarding the association between migraine and risk of dementia. Thus, the study aimed to make a meta-analysis exploring comparison result in different types of cognitive function between migraine patients and non-migraine subjects. In addition, meta-analysis was made to explore the association between migraine and risk of dementia.
Learn More >The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum.
Learn More >To investigate the association of different, selected pain polymorphisms with the presence of de novo long-COVID pain symptoms and to analyze the association between these polymorphisms with clinical, sensory-related, cognitive and psychological variables in COVID-19 survivors.
Learn More >Patients with persistent physical symptoms (PPS) require an explanation that is acceptable and comprehensible to them. Central sensitisation (CS) is an explanatory model for PPS and chronic pain that has been broadly applied in the context of pain medicine, but, until recently, not by general practitioners (GPs). We explored how GPs used the CS model in their consultations with patients with PPS.
Learn More >To investigate the opioid consumption and the healthcare resource utilization in patients with the intrathecal drug delivery system (IDDS) therapy and the comprehensive medical management (CMM) alone.
Learn More >Osteoarthritis (OA) is a common and problematic disorder that is often associated with chronic pain, a combination that renders OA a leading cause of physical disability and an unmet clinical challenge. In this issue of , Liao show that interleukin-6 is a driver of both joint tissue degradation and pain, revealing a common culprit and a possible comprehensive target of therapeutic intervention.
Learn More >Understanding the importance of immigrant entrepreneurship in today's globalized world is crucial for economic, political, and social development. This study is one of the first in the field to explore one immigrant community's entrepreneurship experiences across three different countries. A typology of three different types of immigrant entrepreneurs is identified based on time and space, namely, the displaced, the transnational, and the frustrated. The results show that the UK presents more adverse and racialized experiences for immigrant business start-up in comparison to Denmark and especially Norway. This paper contributes to discourse of intra-ethnic variation, transnationalism, and mixed embeddedness.
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