Acid-induced experimental muscle pain and hyperalgesia with single and repeated infusion in human forearm

Abstract Background and purpose Acid has long been thought to play an important role in the pain process. Animal study showed that repeated acid stimulation induced central sensitization. The purpose of the study is to investigate muscle pain and hyperalgesia evoked byintramuscular infusion of saline at different pH levels, and to compare the effect of a single versus repeated acid infusions. Methods Twenty healthy subjects received infusions of buffered saline (pH 5.0, 6.0, and 7.4) into the brachioradialis muscle in a randomized order. Twelve of the subjects received repeated infusions. The subjects rated the pain intensity on visual analogue scale (VAS). Thermal pain sensitivity, and pressure pain threshold (PPT) were assessed in both arm before, during, immediately after, one hour after, and one day after the infusion. A McGill Pain Questionnaire and pain mapping were completed after each infusion. Results The pH 5 solution caused significantly higher pain and larger areas than pH 6.0 or 7.4. The local PPTs were significantly decreased (hyperalgesia) during and immediately after infusion of all three solutions. No significant differences were detected between the first and second infusion. Conclusions The intensity of acid-induced muscle pain is pH-dependent. All three solutions induced pressure hyperalgesia at the infusion site. Repeated infusions did not induce increased pain or prolonged hyperalgesia as compared with a single injection. Human intramuscular acidic saline infusion could not produce chronic pain model. Implications The acid-induced pain model may reflect the early stage responses to tissue injury of clinical conditions. Repeated intramuscular acidic saline injection model of prolonged hyperalgesia in rodents could not be translated into a human for modelling chronic musculoskeletal pain. </jats:sec

Requirement of fibroblast growth factor 10 in development of white adipose tissue

Fibroblast growth factors (FGFs) are important intercellular signaling molecules in developmental processes. Here, we show that FGF10 is secreted by cultured preadipocytes and that prevention of FGF10 signaling inhibits the expression of C/EBPβ and the subsequent differentiation of these cells. An active form of C/EBPβ rescued differentiation of the cells in which FGF10 signaling was blocked. Development of white adipose tissue and the expression of C/EBPβ in this tissue of FGF10 knockout mice were markedly reduced, and the ability of embryonic fibroblasts derived from FGF10 knockout mice to differentiate into adipocytes was impaired. Therefore, FGF10 plays an important role in adipogenesis, at least partly by contributing to the expression of C/EBPβ through an autocrine/paracrine mechanism

Study on Energy Saving Effect of Housing Polymer Electrolyte Fuel Cell Cogeneration System

Energy saving effect of housing polymer electrolyte fuel cell cogeneration system(PEFC-CGS) which is one of the distributed power source systems was clarified by computer simulation. First, model-based simulations were conducted using heating/cooling load data for air-conditioning and hot water supply demand data that are predicted in an experiment house as the inputs of the simulations to study an optimum operation method of PEFC-CGS. As the result, it is clarified that the DSS Electric Power Load Tracking Operation (PEFC-CGS starts when electric power load is needed and stops when not needed, and it runs in the partial output according to electric power load) is the most efficient. Second, in order to confirm energy saving effect of PEFC-CGS in existent detached house, the computer simulations were conducted using demand data measured in two detached houses located in Fukuoka prefecture. As the result, on one house the energy consumption reduction effect by PEFC-CGS was confirmed

住宅における固体高分子形燃料電池の導入効果に関する研究

Energy saving effect of housing polymer electrolyte fuel cell cogeneration system(PEFC-CGS) which is one of the distributed power source systems was clarified by computer simulation. First, model-based simulations were conducted using heating/cooling load data for air-conditioning and hot water supply demand data that are predicted in an experiment house as the inputs of the simulations to study an optimum operation method of PEFC-CGS. As the result, it is clarified that the DSS Electric Power Load Tracking Operation (PEFC-CGS starts when electric power load is needed and stops when not needed, and it runs in the partial output according to electric power load) is the most efficient. Second, in order to confirm energy saving effect of PEFC-CGS in existent detached house, the computer simulations were conducted using demand data measured in two detached houses located in Fukuoka prefecture. As the result, on one house the energy consumption reduction effect by PEFC-CGS was confirmed

Structure–Activity Relationship Studies and Discovery of a Potent Transient Receptor Potential Vanilloid (TRPV1) Antagonist 4‑[3-Chloro-5-[(1<i>S</i>)‑1,2-dihydroxyethyl]-2-pyridyl]‑<i>N</i>‑[5-(trifluoromethyl)-2-pyridyl]-3,6-dihydro‑2<i>H</i>‑pyridine-1-carboxamide (V116517) as a Clinical Candidate for Pain Management

A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expressing human TRPV1. The most potent of these TRPV1 antagonists were further characterized in pharmacokinetic, efficacy, and body temperature studies. On the basis of its pharmacokinetic, in vivo efficacy, safety, and toxicological properties, compound <b>37</b> was selected for further evaluation in human clinical trials