6-ketoprostaglandin-f1-alpha and Pain

Our aim was to determine the amounts of eicosanoids in blood and synovial tissue of patients with knee arthrosis and to examine the effects of 2 doses of tepoxalin (50 mg twice, 200 mg twice), administered p.o. for 3.5 days. Concentrations of leukotriene B4 (LTB4, LTC4, and thromboxane B2 (TXB2) were measured in blood before and after oral administration of tepoxalin and release of prostaglandin E2 (PGE2), 6-keto-PGF1alpha, and LTC4 was measured in incubation media of synovial tissue, taken at surgery from patients treated with tepoxalin. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids. LT and TXB2 release was reduced by tepoxalin in both doses used. Under these conditions, PGE2, 6-keto-PGF1alpha, and LTC4 release from synovial tissue was detectable only after stimulation with calcium ionophore A23187. Washed synovial tissue, in which tepoxalin concentrations should be reduced, released higher amounts of all eicosanoids measured than directly incubated synovial tissue did. Pain after tepoxalin administration was significantly reduced. Relevant drug concentrations were detected in plasma and synovial fluid. Tepoxalin was well tolerated and had no marked adverse effects. At 400 mg, tepoxalin is a dual inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) in blood and synovial tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthroplasty, Replacement, Knee; Dinoprostone; Double-Blind Method; Drug Administration Schedule; Female; Humans; Knee Joint; Leukotriene Antagonists; Leukotriene B4; Leukotriene C4; Male; Middle Aged; Pain; Pain Measurement; Premedication; Pyrazoles; Radioimmunoassay; Synovial Membrane; Thromboxane B2

Prostaglandin E2 (PGE2), one of the terminal products in the cyclooxygenase pathway, plays an important role in various inflammatory responses. To determine whether selective inhibition of PGE2 may relieve these inflammatory symptoms, we synthesized a selective PGE2 synthesis inhibitor, compound A [1-(6-fluoro-5,7-dimethyl-1,3-benzothiazol-2-yl)-N-[(1S,2R)-2-(hydroxymethyl)cyclohexyl]piperidine-4-carboxamide], then investigated the effects on pyrexia, arthritis and inflammatory pain in guinea pigs. In LPS-stimulated guinea pig macrophages, compound A selectively inhibited inducible PGE2 biosynthesis in a dose-dependent manner whereas enhanced the formation of thromboxane B2 (TXB2). Compound A suppressed yeast-evoked PGE2 production selectively and enhanced the production of TXB2 and 6-keto PGF1αin vivo. In addition, compound A relieved yeast-induced pyrexia and also suppressed paw swelling in an adjuvant-induced arthritis model. The effect on gastrointestinal (GI) ulcer formation was also evaluated and compound A showed a lower GI adverse effect than indomethacin. However, compound A failed to relieve yeast-induced thermal hyperalgesia. These results suggest that selective inhibition of PGE2 synthesis may have anti-pyretic and anti-inflammatory properties without GI side effect, but lack the analgesic efficacy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Benzothiazoles; Depression, Chemical; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fever; Guinea Pigs; Imidazoles; Indomethacin; Inflammation; Macrophages; Pain; Peptic Ulcer; Phenanthrenes; Piperidines; Stimulation, Chemical; Thromboxane B2

To study the therapeutic effects of the series of Muskone (the Muskone includes Slender Dutchmanspipe Root, Tumuxiang, and not Slender Dutchmanspipe Root) on experimental myocardial infarct and pain in rats.. Coronary artery ligation was applied for the model of myocardial infarct. Therapeutic effects were evaluated by measuring parameters of histomorphometry, blood plasm of ET, 6- keto-PGF1alpha and TXB2. Intraperitoneal injection acetic was applied for the model of ache, the frequency and eclipse period of writhing were evaluated its effect of resisting pain.. The Muskone including Radix Aristolociae, the Muskone including Radix Inulae and the Muskone without Radix Aucklandiae all can decrease the area of myocardial infarction in rats, the level of TXB2, ET, and the frequency of writhing significantly. Also it can increase the level 6-keto-PGF1alpha, the ratio of 6-keto-PGF1alpha and TXB2. Single Radix Aristolociae or Radix Inulae only relieved pain.. The Muskone including Radix Aristolociae, the Muskone including Radix Inulae and the Muskone without Radix Aucklandiae all have significant therapeutic effect on both myocardial infarction and pain, while single Radix Aristolociae or Radix Inulae only can relieve pain.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aristolochia; Cycloparaffins; Drug Combinations; Drugs, Chinese Herbal; Endothelins; Female; Inula; Male; Mice; Mice, Inbred ICR; Myocardial Infarction; Pain; Plants, Medicinal; Rats; Rats, Wistar; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Acetic Acid; Analgesics, Non-Narcotic; Animals; Ascitic Fluid; Dinoprostone; Epoprostenol; Indomethacin; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Nociceptors; Pain; Pain Measurement; Receptors, Epoprostenol; Receptors, Prostaglandin

Intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) induced writhing in mice for up to 30 min. During this time, the peritoneal content of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable degradation product of PG12, was highest in the 15-min. sample. In the peritoneal cells, the mRNA expression for the constitutive cyclooxygenase-1 (COX-1) was unchanged by PQ administration. In contrast, little mRNA for COX-2 was detected in the peritoneal cells from unstimulated animals, and was induced 60-120 min. after PQ administration. PGs involved in the induction of writhing thus seem to be derived from a COX-1 reaction. Oral administration of mofezolac, a non-steroidal anti-inflammatory drug which potently inhibits COX-1, suppressed the PQ-induced writhing and peritoneal accumulation of PGs without affecting mRNA expression for both COX isoforms in mice.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoquinones; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Female; Isoenzymes; Isoxazoles; Membrane Proteins; Mice; Pain; Peritoneal Cavity; Prostaglandin-Endoperoxide Synthases; RNA, Messenger

Pretreatment of mice with lipopolysaccharide for 16 h enhanced the number of acetic acid-induced writhing reactions by 2 to 3-fold. In the peritoneal exudates at 10 min after acetic acid injection, 6-keto-prostaglandin F1alpha was detected as a major prostanoid, and this level increased by several-fold by the pretreatment with lipopolysaccharide. The writhing reaction and the prostaglandin formation were almost completely suppressed by indomethacin. However, the lipopolysaccharide-induced enhancement of writhing reaction and an increment of 6-keto-prostaglandin F1alpha level were diminished by the administration of cyclooxygenase-2-selective inhibitors, such as NS-398, nimesulide, or L-745337, to a level similar to the mice that did not receive lipopolysaccharide. Cyclooxygenase-2 protein in the exudates became detectable at 5-48 h after the lipopolysaccharide-pretreatment. These results suggest that the increased prostaglandin production by cyclooxygenase-2 could be responsible for enhancement of the acetic acid-induced writhing reaction by lipopolysaccharide pretreatment.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Induction; Exudates and Transudates; Indans; Indomethacin; Isoenzymes; Male; Mice; Mice, Inbred ICR; Nitrobenzenes; Pain; Pain Measurement; Peritoneum; Prostaglandin-Endoperoxide Synthases; Sulfonamides

Prostaglandin levels in plasma and peritoneal fluid were determined in 10 sterilized women with pelvic pain without pathological findings. Another 15 healthy women were regarded as controls. The 6-keto-PGF1 alpha levels in peritoneal fluid collected from patients with pelvic pain were significantly higher than that from the controls (p less than 0.05). The results indicated that prostaglandins might play an important role in pelvic pain following sterilization.. Prostaglandin (PG) levels in plasma and peritoneal fluid were determined in 10 sterilized women with pelvic pain without pathological findings. Another 15 women who were healthy were regarded as controls. The 6-keto-PGF(1alpha) levels in peritoneal fluid collected from patients with pelvic pain were significantly higher than that from controls (p 0.05. The results indicated that PGs might play an important role in pelvic pain following sterilization.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Dinoprost; Female; Humans; Pain; Pelvis; Peritoneal Cavity; Prostaglandins; Prostaglandins E; Radioimmunoassay; Reference Values; Sterilization, Tubal; Thromboxane B2

The relationship between the kaolin-induced writhing reaction and production of arachidonate metabolites (PGs) in mice was studied. PGs were released into the peritoneal cavity after intraperitoneal injection (i.p.) of kaolin (2.5 mg/mouse) with a peak at 5 min. About 80% of the total amount was 6-keto-PGF1 alpha. There was a significant correlation (r = 0.8237, p less than 0.001) between the number of writhes and the amount of 6-keto-PGF1 alpha. The writhing reaction induced by kaolin was significantly inhibited by simultaneous injection of soybean trypsin inhibitor (SBTI; 2.5 mg/mouse) and increased by simultaneous injection of captopril (50 micrograms/mouse). The writing reaction induced by kaolin which was inhibited by oral administration of indomethacin (1 mg/kg) was restored by exogenous i.p. injection of PGI2-Na (2-10 ng/mouse). Indomethacin, ibuprofen and alminoprofen inhibited the writhing reaction and reduced the level of peritoneal 6-keto-PGF1 alpha in parallel manner. Tiaramide, pentazocine and morphine inhibited the writhing reaction without reducing the revels of 6-keto-PGF1 alpha. These results differentiate the site of action of these analgesics. They suggest that the mechanism of the kaolin-induced writhing reaction in mice involves a synergic pain caused by simultaneously released bradykinin and PGI2. This model is a useful tool which allows differentiation of mode of action of analgesics by simultaneous determination of the writhing response and peritoneal 6-keto-PGF1 alpha.

Topics: 6-Ketoprostaglandin F1 alpha; Analgesics; Animals; Captopril; Epoprostenol; Indomethacin; Kaolin; Male; Mice; Mice, Inbred ICR; Pain; Peritoneal Cavity; Peritoneal Lavage; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Trypsin Inhibitors

Peritoneal fluid obtained at laparoscopy from 49 women was measured for its content of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-KF), and thromboxane B2 (TxB2) by specific radioimmunoassays. In normal women (n = 10), the concentrations of prostaglandins in peritoneal fluid were (mean +/- SE): PGE2 = 0.79 +/- 0.26, PGF2 alpha = 0.60 +/- 0.18, 6-KF = 0.48 +/- 0.19, and TxB2 = 0.23 +/- 0.09 ng/ml; in women with endometriosis (n = 16): PGE2 = 1.43 +/- 0.72, PGF2 alpha = 1.52 +/- 0.59, 6-KF = 3.32 +/- 0.71, and TxB2 = 1.14 +/- 0.69 ng/ml; in women with chronic pelvic inflammatory disease and/or obstructed tubes (n = 19): PGE2 = 1.94 +/- 1.04, PGF2 alpha = 1.20 +/- 0.61, 6-KF = 1.55 +/- 0.40, and TxB2 = 0.64 +/- 0.24 ng/ml; in women with pelvic pain without any visible pathologic condition (n = 4): PGE2 = 1.11 +/- 0.66, PGF2 alpha = 0.73 +/- 0.55, 6-KF = 1.35 +/- 0.35, and TxB2 = 0.39 +/- 0.17. The mean volumes of peritoneal fluid recovered were 10 to 16 ml and were not significantly different between the groups. Except for a significantly elevated concentration of 6-KF in the peritoneal fluid of women with endometriosis compared to normal women (p = less than 0.02), the prostaglandins measured did not differ significantly between the groups of women studied. The possible significance of elevated 6-KF in the peritoneal fluid of women with endometriosis is discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Ascitic Fluid; Chronic Disease; Dinoprost; Dinoprostone; Endometriosis; Epoprostenol; Female; Humans; Pain; Pelvic Inflammatory Disease; Pelvis; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2