ABSTRACT
Nonsteroidal anti-inflammatory drugs and acetaminophen are cyclooxygenase inhibitors commonly used as symptomatic medicines for myofascial pain syndrome. Using the selective inhibitors celecoxib and zaltoprofen, cyclooxygenase-2 has been shown to be involved in the initiation, but not the maintenance, of muscular mechanical hyperalgesia induced by lengthening contractions, which serves as a useful model for the study of myofascial pain syndrome. The effect of other cyclooxygenase-2 inhibitors, such as acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen, on muscular mechanical hyperalgesia during maintenance has not been studied. Here, we examined the analgesic effects of the nonsteroidal anti-inflammatory drugs and acetaminophen on the model. Consistent with previous studies, mechanical withdrawal threshold of the muscle was significantly decreased and reached its lowest level 24 h after lengthening contractions. Celecoxib had no effect on muscular mechanical hyperalgesia, when orally administered 24 h after lengthening contractions. In contrast, acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen increased the withdrawal threshold, which had decreased by lengthening contractions, in a dose-dependent manner. These results demonstrate the analgesic actions of nonsteroidal anti-inflammatory drugs and acetaminophen in the maintenance process of lengthening contraction-induced muscular mechanical hyperalgesia, which may occur through cyclooxygenase-2 independent mechanisms.
Subject(s)
Acetaminophen/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase 2/metabolism , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Muscle Contraction , Muscle, Skeletal/physiopathology , Acetaminophen/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Celecoxib/pharmacology , Celecoxib/therapeutic use , Male , Muscle Contraction/drug effects , Rats, Sprague-Dawley , Time FactorsABSTRACT
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofen-induced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1ß (IL-1ß), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofen-induced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen.
Subject(s)
Acetaminophen/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Gastric Mucosa/drug effects , Ibuprofen/adverse effects , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase Inhibitors/therapeutic use , Acetaminophen/administration & dosage , Administration, Oral , Animals , Cytokines/genetics , Cytokines/metabolism , Dose-Response Relationship, Drug , Gastric Mucosa/enzymology , Gastric Mucosa/pathology , Gene Expression Profiling , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase Inhibitors/administration & dosage , Peptic Ulcer Hemorrhage/chemically induced , Peptic Ulcer Hemorrhage/enzymology , Peptic Ulcer Hemorrhage/pathology , Peptic Ulcer Hemorrhage/prevention & control , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Stomach Ulcer/chemically induced , Stomach Ulcer/enzymology , Stomach Ulcer/pathology , Stomach Ulcer/prevention & controlABSTRACT
12CaO·7Al2O3 electride, a sub-nanoporous compound having a work function of 2.4 eV, was examined as a candidate cathode material in fluorescent lamps. The electron emission yield was higher and the discharge voltage was lower for 12CaO·7Al2O3 than for existing cathode materials such as Ni, Mo or W; therefore, the energy consumption of the fluorescent lamps can be improved using 12CaO·7Al2O3 cathodes. Prototype glow-discharge lamps using 12CaO·7Al2O3 were constructed and exhibited reasonable durability.
