Accepted

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral μ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.

Pain is common in people with dementia, and pain can exacerbate the behavioural and psychological symptoms of dementia. Effective pain management is challenging, not least in people with dementia. Impairments of cognition, communication and abstract thought can make communicating pain unreliable or impossible. It is unclear which biopsychosocial interventions for pain management are effective in people with dementia, and which interventions for behavioural and psychological symptoms of dementia are effective in people with pain. The result is that drugs, physical therapies and psychological therapies might be either underused or overused. People with dementia and pain could be helped by assessment processes that characterise an individual's pain experience and dementia behaviours in a mechanistic manner, phenotyping. Chronic pain management has moved from a 'one size fits all' approach, towards personalised medicine, where interventions recommended for an individual depend upon the key mechanisms underlying their pain, and the relative values they place on benefits and adverse effects. Mechanistic phenotyping through careful personalised evaluation would define the mechanisms driving pain and dementia behaviours in an individual, enabling the formulation of a personalised intervention strategy. Central pain processing mechanisms are particularly likely to be important in people with pain and dementia, and interventions to accommodate and address these may be particularly helpful, not only to relieve pain but also the symptoms of dementia.

Psoriasis is a chronic, autoimmune, and non-communicable skin disease with a worldwide prevalence rate of 2-3%, creating an economic burden on global health. Some significant risk factors associated with psoriasis include genetic predisposition, pathogens, stress, medications, etc. In addition, most patients with psoriasis should also deal with comorbidities such as psoriatic arthritis, inflammatory bowel diseases, cardiovascular diseases, and psychological conditions, including suicidal thoughts. Based on its severity, the treatment approach for psoriasis is categorised into three types, i.e., topical therapy, systemic therapy, and phototherapy. Topical therapy for mild to moderate psoriasis faces several issues, such as poor skin permeability, low skin retention of drug formulation, greasy texture of topical vehicle, lack of controlled release, and so on. On the other arrow, systemic therapy via an oral or parenteral route of drug administration involves numerous drawbacks, including first-pass hepatic metabolism, hepatotoxicity, gastrointestinal disturbances, needle pain and phobia, and requirement of healthcare professional to administer the drug. To overcome these limitations, researchers devised a microneedle-based drug delivery system for treating mild to moderate and moderate to severe psoriasis. A single microneedle system can deliver the anti-psoriatic drugs either locally (topical) or systemically (transdermal) by adjusting the needle height without involving any pain. In this contemplate, the current review provides concise information on the pathophysiology, risk factors, and comorbidities of psoriasis, followed by their current treatment approaches and limitations. Further, it meticulously discusses the potential of microneedles in psoriasis therapy and diagnosis, along with descriptions of their patents and clinical trials.

The Chronic Headache Education and Self-Management Study (CHESS) multicentre randomised trial evaluated the impact a group education and self-management support intervention with a best usual care plus relaxation control for people living with chronic headache disorders (tension type headaches or chronic migraine, with or without medication overuse headache). Here we report the process evaluation exploring potential explanations for the lack of positive effects from the CHESS intervention.

It is documented that some of the opioids prescribed to manage chronic pain are diverted and used for nonmedical purposes. We investigated whether a skill-based, chronic pain management (CPM) educational program could improve first-year family medicine residents' comfort, knowledge, and concerns in assessing and managing patients who use opioids for chronic noncancer pain.

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and leads to an imbalance between anabolic and catabolic processes in articular cartilage; however, the complexity of the network between inflammatory factors that often involves positive and negative feedback loops makes current anti-cytokine therapy ineffective. MicroRNAs (miRNAs) have emerged as key regulators to control inflammation, and aberrant miRNAs expression has recently been linked to OA pathophysiology. In the present study, we characterized transcriptomic profiles of miRNAs in primary murine articular chondrocytes in response to a proinflammatory cytokine, IL-1β, and identified as the most responsive miRNA to IL-1β. was also found to be upregulated in human OA cartilage. We further demonstrated that knockdown of antagonized IL-1β-mediated inflammatory responses and IL-1β-induced catabolism in vitro, and silencing of in chondrocytes ameliorated articular cartilage destruction and reduced OA-evoked pain in an injury-induced murine OA model. Moreover, parallel RNA sequencing revealed that differentially expressed genes in response to IL-1β were enriched in pathways related to inflammatory processes, cartilage matrix homeostasis, and cell metabolism. Bioinformatic analyses of putative gene targets and following prediction of protein-protein interactions suggest a functional role of in mediating inflammatory processes and regulation of cartilage homeostasis. Our genetic and transcriptomic data define a crucial role of in OA pathogenesis and implicate modulation of in articular chondrocytes as a potential therapeutic strategy to alleviate OA.