Gabapentin is used as an effective drug for relieving pain, but the main mechanism is still unclear. Recently, voltage-gated Ca2+ channel subunits are suggested for the main target for the analgesic action of gabapentin. We wonder whether gabapentin directly modulates other specific ion channels peripherally expressed in the sensory neurons. To test this, we used a heterologous expression system in which the cell lines transiently expressed thermosensitive transient receptor potential ion channels (thermoTRPs) as well as the primary cultured mouse trigeminal neurons. The application of gabapentin reduced the increases in the intracellular Ca2+ level caused by TRPA1 activation in the heterologous expression system whereas the responses via actions of other thermoTRPs were not dramatically affected by the gabapentin treatment. Gabapentin also attenuated the TRPA1-mediated intracellular Ca2+ increases in the cultured trigeminal neurons. These findings suggest TRPA1 in the peripheral sensory neurons as a novel target for the analgesic of gabapentin.
Acrolein ; Amines ; Animals ; Cell Line ; Cyclohexanecarboxylic Acids ; gamma-Aminobutyric Acid ; Ion Channels ; Mice ; Neurons ; Sensory Receptor Cells ; Trigeminal Ganglion

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disorder that has many symptoms. Gastrointestinal symptoms are common, while colonic involvement in the form of ischemic colitis or a colonic ulcer is rare in SLE. The differential diagnosis of ischemic proctitis with ulceration includes an infected ulcer, ulcerative colitis, Crohn's disease, solitary rectal ulcer colitis, malignant tumor, and lupus colitis. Here, we report a 22-year-old male with abdominal pain and diarrhea, who had a huge rectal ulcer that nearly obstructed the rectosigmoid junction. This turned out to be a rare gastrointestinal manifestation of lupus. He recovered after being treated with high-dose oral steroids. Our case demonstrates that a rectal ulcer is a rare, but important, complication of SLE and can be the initial clinical manifestation of the disease.
Abdominal Pain ; Colitis ; Colitis, Ischemic ; Colitis, Ulcerative ; Colon ; Crohn Disease ; Diagnosis, Differential ; Diarrhea ; Humans ; Lupus Erythematosus, Systemic ; Male ; Proctitis ; Steroids ; Ulcer ; Young Adult

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disorder that has many symptoms. Gastrointestinal symptoms are common, while colonic involvement in the form of ischemic colitis or a colonic ulcer is rare in SLE. The differential diagnosis of ischemic proctitis with ulceration includes an infected ulcer, ulcerative colitis, Crohn's disease, solitary rectal ulcer colitis, malignant tumor, and lupus colitis. Here, we report a 22-year-old male with abdominal pain and diarrhea, who had a huge rectal ulcer that nearly obstructed the rectosigmoid junction. This turned out to be a rare gastrointestinal manifestation of lupus. He recovered after being treated with high-dose oral steroids. Our case demonstrates that a rectal ulcer is a rare, but important, complication of SLE and can be the initial clinical manifestation of the disease.
Abdominal Pain ; Colitis ; Colitis, Ischemic ; Colitis, Ulcerative ; Colon ; Crohn Disease ; Diagnosis, Differential ; Diarrhea ; Humans ; Lupus Erythematosus, Systemic ; Male ; Proctitis ; Steroids ; Ulcer ; Young Adult

(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to β-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-κB activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-α (TNF-α) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-κB-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-κB and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.
Chalcone* ; Genes, Reporter ; HEK293 Cells ; Luciferases ; Macrophages ; Necrosis ; Nitric Oxide ; Nitric Oxide Synthase ; Phosphotransferases* ; RNA, Messenger ; Transcription Factor AP-1