British journal of pharmacology
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Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2 ) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain. ⋯ The prokineticin system contributes to pain modulation via neuron-glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.
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Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ-organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. ⋯ Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis.
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Sepsis is a clinical condition characterized by overwhelming systemic inflammation with high mortality rate and high prevalence, but effective treatment is still lacking. Toll-like receptor 3 (TLR3) is an endogenous sensor, thought to regulate the amplification of immune response during sepsis. Modulators of TLR3 have an advantage in the treatment of sepsis. Here, we aimed to explore the mechanism of a monosubstituted 1,2-benzenediamine derivative FC-99 {N(1) -[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine}on modulating TLR3 expression and its therapeutic potential on mouse model of sepsis. ⋯ FC-99 reversed TLR3 expression and ameliorate CLP-induced sepsis in mice. Thus, FC-99 will be a potential therapeutic candidate for sepsis.
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This themed issue of Br J Pharmacol is dedicated to the utility and needs of animal models in psychiatry research. The following articles document strengths and weaknesses, indicate areas where better models are sorely needed and provide examples where pharmacological studies may result in mechanistic breakthrough and aid in drug development. In addition, complicating factors both in disease and treatment strategies are canvassed, such as sex differences, genetic and environmental influences. While not exhaustive, the intention was to use a number of exemplars to stimulate discussion around how animal models can aid in improving our understanding and treatment of many devastating conditions.
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Similarities between laboratory animals and humans in anatomy and physiology of the cephalic nociceptive pathways have allowed scientists to create successful models that have significantly contributed to our understanding of headache. They have also been instrumental in the development of novel anti-migraine drugs different from classical pain killers. Nevertheless, modelling the mechanisms underlying primary headache disorders like migraine has been challenging due to limitations in testing the postulated hypotheses in humans. ⋯ Headache and migraine-like episodes induced by administration of glyceryltrinitrate and CGRP to humans and parallel behavioural and biological changes observed in rodents create interesting possibilities for translational research. Not unexpectedly, species differences and model-specific observations have also led to controversies as well as disappointments in clinical trials, which, in return, has helped us improve the models and advance our understanding of headache. Here, we review commonly used headache and migraine models with an emphasis on recent developments.