dinoprost and Pain

The purpose of this study was to determine muscle and tendon protein fractional synthesis rates (FSR) at rest and after a one-legged kicking exercise in patients with knee osteoarthritis (OA) receiving either placebo or nonsteroidal anti-inflammatory drugs (NSAIDs).. Twenty patients with knee OA (50-70 yr) were enrolled. For each of the 3 days before the exercise intervention, 9 patients were administered NSAIDs (1200 mg), and 11 patients were administered placebo in a double-blinded manner. Each patient performed 60 min of one-legged kicking at 55% of workload maximum while the contralateral leg remained rested. Twenty-four hours after exercise, we determined circulating concentrations of inflammatory parameters and measured FSR of myofibrillar and sarcoplasmic protein fractions of vastus lateralis muscle and patellar tendon collagen protein by the direct incorporation method using a flooding dose of 13C/12C-proline.. Circulating levels of prostaglandin F2α were lower in the NSAID group compared with the placebo group (P < 0.05). There was an overall significant effect of exercise on FSR in muscle myofibrillar (P = 0.003) and sarcoplasmic protein (P = 0.026) but not in tendon collagen protein (P = 0.52). No overall significant effect of the drug was seen on either of the tissue protein fractions (P > 0.05) or on the interaction between the drug and exercise on FSR in tendon collagen (P = 0.21), muscle myofibrillar (P = 0.68), or sarcoplasmic protein, FSR (P = 0.16).. In elderly patients with knee OA, an acute bout of moderate exercise significantly increases FSR of muscle myofibrillar and sarcoplasmic protein, but not tendon collagen, 24 h after exercise. NSAID administration in patients with knee OA reduced the level of circulating prostaglandin F2α but did not diminish the exercise-induced response of muscle contractile protein FSR. However, we cannot exclude that a minor inhibition of muscle sarcoplasmic proteins may have been present with NSAID treatment. This study suggests that muscle hypertrophy after long-term training is not influenced by NSAIDs.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Body Mass Index; Dinoprost; Exercise; Female; Humans; Male; Middle Aged; Muscle Proteins; Muscle, Skeletal; Osteoarthritis, Knee; Pain; Severity of Illness Index; Treatment Outcome

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.

Topics: Acetylcysteine; Adult; Antioxidants; Ascorbic Acid; Bleomycin; Creatine Kinase; Dinoprost; Double-Blind Method; Exercise; F2-Isoprostanes; Glutathione Peroxidase; Humans; Interleukin-6; Iron; L-Lactate Dehydrogenase; Lipid Peroxidation; Lipid Peroxides; Male; Muscle, Skeletal; Myoglobin; Myositis; Oxidative Stress; Pain; Peroxidase; Placebos; Superoxide Dismutase

Following the demonstration that increased prostaglandin F2 alpha production causes pain similar to dysmenorrhea, and the finding that prostaglandin synthetase inhibitors are capable of relieving menstrual pain, the early theory of uterine ischemia has once again gained support as the most likely explanation for this condition. In a double-blind, placebo-controlled, crossover study, 30 of 43 women with moderate to severe dysmenorrhea who completed the trial preferred flurbiprofen (Ansaid, Upjohn), a potent new analgesic/anti-inflammatory agent (50 mg four times daily), to aspirin (650 mg four times daily) and placebo. Flurbiprofen was also rated superior to aspirin and placebo in the degree of pain relief. An algorithm for the diagnosis and treatment of 90 percent of women with primary dysmenorrhea is presented.

Topics: Adolescent; Adult; Aspirin; Dinoprost; Dysmenorrhea; Female; Flurbiprofen; Humans; Middle Aged; Pain; Propionates; Prostaglandins F

Akebiae Fructus, a Tujia minority folk medicine and a well-known traditional Chinese medicine for soothing the liver, regulating Qi, promoting blood circulation and relieving pain, is widely used in the treatment of primary dysmenorrhea. However, little is known about its underlying mechanism.. To explore the effect of Akebiae Fructus on primary dysmenorrhea model induced by estradiol benzoate and oxytocin, and to provide better understanding of the mechanism of Akebiae Fructus for primary dysmenorrhea treatment.. The primary dysmenorrhea mouse model was used in this study. Except for the control group and the normal administration group, the mice of other groups were subcutaneously injected with estradiol benzoate (10 mg/kg/d) for 10 consecutive days. From the 5th day of the ten-day model period, the positive control groups were given 0.075 g/kg ibuprofen and 7.5 g/kg Leonurus granule, the drug groups were given 0.2 g/kg, 0.4 g/kg, 0.8 g/kg Akebiae Fructus extract, the normal administration group was given 0.8 g/kg Akebiae Fructus extract, and the same volume saline was given in the control group. On the tenth day, oxytocin (10 U/kg) was peritoneally injected after estradiol benzoate injected 1 h. After the oxytocin injection, writhing behavior was observed for 30 min. Then the uterine tissue was collected to measure the level of PGF. Akebiae Fructus inhibited the writhing, decreased the PGF. Akebiae Fructus could effectively alleviate the symptoms of primary dysmenorrhea, regulate metabolic disorders, and control the related gene expression in primary dysmenorrhea. The study may provide clues for further study of Akebiae Fructus treatment on primary dysmenorrhea.

Topics: Animals; Benzoates; Biomarkers; Dinoprost; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Dysmenorrhea; Female; Gene Expression Regulation; Inflammation; Medicine, Chinese Traditional; Metabolic Networks and Pathways; Metabolome; Mice, Inbred ICR; Oxytocin; Pain; Ranunculales; Transcriptome; Uterine Contraction; Uterus

Several studies have evaluated the effects of high-intensity aerobic training (HIAT) on pain severity and quality of life (QoL) among women with primary dysmenorrhea. However, to date, no studies have evaluated the effectiveness of HIAT on academic performance or absenteeism or examined the cost-effectiveness of HIAT relative to other treatments in women with primary dysmenorrhea. Furthermore, the mechanisms underlying aerobic exercise-induced analgesia in primary dysmenorrhea remain unclear. The objectives of this study are to: (1) evaluate the effects of HIAT on absenteeism and academic performance among university students, (2) identify the underlying mechanisms associated with aerobic exercise-induced analgesia in primary dysmenorrhea, and (3) determine the cost-effectiveness of HIAT compared with a wait-list control (WLC) group receiving usual care.. A sequential, embedded, mixed-methods study design, including a crossover, randomised controlled trial (RCT) and semi-structured focus groups, will be conducted alongside an economic evaluation. A total of 130 women aged 18-24 years will be randomised into either HIAT (n = 65) or wait-list control (n = 65) groups. Primary outcomes will include average pain intensity, absenteeism from university, and academic performance. Primary mediators will include salivary progesterone and prostaglandin F2α levels. Outcome and meditator variables will be assessed at baseline and post-treatment, at 12 and 28 weeks. An economic analysis will be conducted from the societal and healthcare perspective of Hong Kong. Semi-structured focus groups will be conducted at 32 weeks. Of the 130 participants included in the RCT, 70 will be included in the focus groups.. All statistical analyses will be performed on an intention-to-treat basis, using SPSS (version 24). Preliminary analysis using an independent samples t-test and a two-sided, unpaired Student's t-test will be performed to exclude carryover effects and identify within-participant differences in outcome variables between the study periods, respectively. Treatment effects will be evaluated using analysis of variance via a mixed-effects model with fixed effects for intervention, period, and sequence. In all models, random effects will include the participants nested within the sequence as a sampling cluster. The mediation effects will be assessed using the Sobel test. The EQ-5D responses will be converted into utility scores to estimate the gain or loss of quality-adjusted life-years. Seemingly unrelated regression analyses will be used to estimate the total cost differences and effect differences. Qualitative data will be analysed using the process of thematic analysis.

Topics: Absenteeism; Academic Performance; Adolescent; Cost-Benefit Analysis; Cross-Over Studies; Dinoprost; Dysmenorrhea; Exercise; Feasibility Studies; Female; Focus Groups; Humans; Pain; Progesterone; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Students; Universities; Young Adult

The primary objective of the study was to evaluate the correlation between prostaglandin F2-alpha and tumour necrosis factor-alpha concentration and that of pain experienced by patients undergoing thermal balloon ablation. Furthermore we evaluated the correlation between the endometrial and myometrial thicknesses and the degree of pain experienced by patients undergoing the procedure, and in addition the correlation between PGF2-alpha, TNF-alpha and endometrial and myometrial thicknesses. Single-arm cohort study (Canadian Task force classification II-2). In University Medical Centre Ljubljana, outpatient setting, 40 perimenopausal women with dysfunctional uterine bleeding (DUB), underwent endometrial thermal balloon ablation. The thickness of the endometrium and myometrium was measured prior to surgery using a transvaginal ultrasound that provided cross-sectional images. The degree of pain was rated using the visual analogue scale (VAS) and numeric rating scale (NRS) immediately and 60 minutes after the procedure. The concentration of PGF2-alpha and TNF-alpha in venous blood was measured prior to, at the end of and 60 minutes after the procedure. The results showed a positive correlation between the concentration of PGF2-alpha released during endometrial ablation and the endometrial and myometrial thickness (p > 0.01), including the reported degree of pain (p > 0.01). The concentration of TNF-alpha indicates a positive correlation with the level of pain (p > 0.05), but is not dependent on the thicknesses of the endometrium and myometrium. Endometrial thickness correlates to the degree of pain and the prostaglandin F2-alpha concentration. In clinical practice, performing the Gynecare ThermaChoice procedure immediately after menstruation or preoperative preparation of the endometrium using oral contraceptives enables this procedure to be performed in outpatient settings and can be considered a valuable treatment option for DUB.

Topics: Adult; Dinoprost; Endometrial Ablation Techniques; Female; Humans; Middle Aged; Pain; Pain Measurement; Tumor Necrosis Factor-alpha

We describe the effects of multi-day relay trail running on muscle soreness and damage, and systemic immune, inflammatory, and oxidative responses. 16 male and 4 female athletes ran 894 km in 47 stages over 95 h, with mean (SD) 6.4 (1.0) stages per athlete and 19.0 (1.7) km per stage. We observed post-pre run increases in serum creatine kinase (qualified effect size extremely large, p = 0.002), IL-6 (extremely large, p < 0.001), urinary 8-isoprostane/creatinine (extremely large, p = 0.04), TNF-α (large, p = 0.002), leukocyte count (very large, p < 0.0001) and neutrophil fraction (very large, p < 0.001); and reductions in hemoglobin (moderate, p < 0.001), hematocrit (moderate, p < 0.001), and lymphocyte fraction (trivial, p < 0.001). An increase in ORAC total antioxidant capacity (TAC, small, p = 0.3) and decrease in urinary 8-OHdG/creatinine (small, p = 0.1) were not statistically significant. During the run, muscle soreness was most frequent in the quadriceps. The threshold for muscle pain (pain-pressure algometry) in the vastus lateralis and gastrocnemius was lower post-run (small, p = 0.04 and 0.03). Average running speed was correlated with algometer pain and leukocyte count (large, r = 0.52), and TAC was correlated with IL-6 (very large, r = 0.76) and 8-isoprostane/creatinine (very large, r = -0.72). Multi-day stage-racing increases inflammation, lipid peroxidation, muscle damage and soreness without oxidative DNA damage. High TAC is associated with reduced exercise-induced lipid peroxidation, but is not related to immune response or muscle damage.

Topics: Adult; Antioxidants; Creatine Kinase; Dinoprost; Exercise; Female; Humans; Inflammation; Interleukin-6; Lipid Peroxidation; Male; Muscle, Skeletal; Oxidative Stress; Pain; Running

It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2 in the spinal cord of rats with kaolin/λ-carrageenan-induced knee inflammation, and that this mechanism contributes to the analgesic effects of COX-2 inhibitors in this experimental model. We report the development of a specific method for the identification of endocannabinoid COX-2 metabolites, its application to measure the levels of these compounds in tissues, and the finding of prostamide F(2α) (PMF(2α)) in mice with knee inflammation. Whereas the levels of spinal endocannabinoids were not significantly altered by kaolin/λ-carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA, PMF(2α), were strongly elevated. The formation of PMF(2α) was reduced by indomethacin (a non-selective COX inhibitor), NS-398 (a selective COX-2 inhibitor) and SC-560 (a selective COX-1 inhibitor). In healthy mice, spinal application of PMF(2α) increased the firing of nociceptive (NS) neurons, and correspondingly reduced the threshold of paw withdrawal latency (PWL). These effects were attenuated by the PMF(2α) receptor antagonist AGN211336, but not by the FP receptor antagonist AL8810. Also prostaglandin F(2α) increased NS neuron firing and reduced the threshold of PWL in healthy mice, and these effects were antagonized by AL8810, and not by AGN211336. In mice with kaolin/λ-carrageenan-induced knee inflammation, AGN211336, but not AL8810, reduced the inflammation-induced NS neuron firing and reduction of PWL. These findings suggest that inflammation-induced, and prostanoid-mediated, enhancement of dorsal horn NS neuron firing stimulates the production of spinal PMF(2α), which in turn contributes to further NS neuron firing and pain transmission by activating specific receptors.

Topics: Action Potentials; Animals; Arachidonic Acids; Cannabinoid Receptor Modulators; Chromatography, Liquid; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprost; Dinoprostone; Endocannabinoids; Evoked Potentials; Hindlimb; Inflammation; Mass Spectrometry; Membrane Proteins; Mice; Nociceptors; Pain; Polyunsaturated Alkamides; Posterior Horn Cells; Rats

Nociceptive primary afferents have the capacity to induce a state of increased excitability in the dorsal horn neurons of the spinal cord. It is well accepted that capsaicin-sensitive C-fibers transduce noxious stimulation and acute pain and that capsaicin-insensitive A beta-fibers are responsible for touch and innocuous sensation. It has been reported that the intrathecal (i.t.) administration of prostaglandin F(2 alpha) (PGF(2 alpha)) and ATP induces mechanical allodynia via the capsaicin-insensitive primary afferent pathway. In the present study, we investigated the interaction of purinoceptor P2X and the PGF(2 alpha) receptor (FP) in the induction of allodynia by use of mice lacking FP (FP(-/-)). Both PGF(2 alpha) and the P2X receptor agonist alphabeta-methylene ATP administered i.t. strongly induced allodynia for 50 min by tactile stimuli to the flank of mice. The allodynia induced by alphabeta-methylene ATP, but not that by PGF(2 alpha), was suppressed by simultaneous i.t. administration of P2X receptor antagonists pyridoxalphosphate-6-azophenyl-2,4-disulphonic acid and A-317491. In contrast, the allodynia induced by alphabeta-methylene ATP as well as that by PGF(2 alpha) was not observed in FP(-/-) mice. Immunostaining of beta-galactosidase, a reporter knocked into the endogenous FP locus in FP(-/-) mice, showed that the FP receptor was co-localized with P2X(2) and P2X(3) receptors in neurons of the spinal cord. alphabeta-Methylene ATP evoked a transient or sustained [Ca(2+)](i) increase in most of the PGF(2 alpha)-responsive cells in the deeper layer of the spinal cord, and the alphabeta-methylene ATP-evoked increase was blocked by the FP receptor antagonist AL-8810 in two-thirds of the cells. Neither PGF(2 alpha) nor alphabeta-methylene ATP induced the activation of spinal microglia. The present study demonstrates that the alphabeta-methylene ATP-evoked allodynia is mediated by the FP receptor, possibly via the functional coupling between the activation of P2X(2/3) receptors on the central terminal of capsaicin-insensitive fibers and FP receptors on spinal neurons.

Topics: Adenosine Triphosphate; Afferent Pathways; Animals; Calcium Signaling; Dinoprost; Galactosides; Genes, Reporter; Hyperalgesia; Indoles; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nociceptors; Pain; Posterior Horn Cells; Presynaptic Terminals; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Receptors, Prostaglandin; Receptors, Purinergic P2; Receptors, Purinergic P2X2; Receptors, Purinergic P2X3; Spinal Nerve Roots

Prostaglandin F2alpha (PGF2alpha) binds to its receptor (FP) to increase the intracellular-free calcium concentration ([Ca2+]i) by coupling of FP with Gq protein. Spinal intrathecal administration of PGF2alpha to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent Abeta-fibres and N-methyl-d-aspartate receptor epsilon 4 subunit are involved. FP in the spinal cord, however, was not well characterized. Here, we showed constitutive expression of FP mRNA in mouse spinal cord, and functionally characterized spinal FP-expressing cells which were involved in PGF2alpha-induced mechanical allodynia. The method for repetitive administration of oligodeoxyribonucleotides through tubing to conscious mice was established for mechanical allodynia evaluation. We identified an antisense oligodeoxyribonucleotide targeting FP mRNA, causing both disappearance of PGF2alpha-induced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF2alpha rapidly increased [Ca2+]i of the cells in the deeper layer of the dorsal horn. In contrast, when the FP antisense oligodeoxyribonucleotide was repeatedly administered, the population of PGF2alpha-responsive cells in the slices reduced, and PGF2alpha-induced [Ca2+]i increase of these cells diminished. These data strongly suggested that, in the dorsal horn of the spinal cord, there are the FP-expressing cells which are involved in PGF2alpha-induced mechanical allodynia.

Topics: Animals; Calcium; Dinoprost; Hyperalgesia; In Vitro Techniques; Injections, Spinal; Mice; Oligonucleotides, Antisense; Pain; Receptors, Prostaglandin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spinal Cord; Touch

The contribution of nitric oxide (NO) to articular pain in arthritis induced by zymosan (1 mg, intra articular) in rats was assessed by measuring articular incapacitation (AI). Systemic treatment with the non-selective NO synthase (NOS) inhibitor L-NAME (10 - 100 mg kg(-1) i.p.) or with the selective iNOS inhibitors aminoguanidine (AG; 10 - 100 mg kg(-1) i.p.) or 1400W (0.5 - 1 mg kg(-1) s.c.) inhibited the AI induced by injection of zymosan 30 min later. Local (intra articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1 - 1 micromol; 1400W, 0.01 (micromol) 30 min before zymosan also inhibited the AI. Systemic or local treatment with the NOS inhibitors (L-NAME; AG, 100 mg kg(-1) i.p. or 0.1 micromol joint(-1); 1400W, 1 mg kg(-1) s.c. or 0.01 micromol joint(-1)), 2 h after zymosan did not affect the subsequent AI. Local treatment with the NO donors SNP or SIN-1, 2 h after zymosan did inhibit AI. L-NAME and AG, given i.p. inhibited nitrite but not prostaglandin E(2) (PGE(2)) levels in the joints. L-NAME (100 mg kg(-1)) but not AG (100 mg kg(-1)) increased mean arterial blood pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema induced by zymosan. In conclusion, inhibitors of iNOS decrease pain in zymosan arthritis only when given before the zymosan. This was not due to inhibition of articular PGE(2) release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema.

Topics: Amidines; Animals; Arthritis, Experimental; Benzylamines; Cartilage, Articular; Dinoprost; Edema; Enzyme Inhibitors; Guanidines; Injections, Intra-Articular; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pain; Pain Measurement; Rats; Rats, Wistar; Zymosan

Glutamate is the main excitatory neurotransmitter in the central nervous system and has been shown to be involved in spinal nociceptive processing. We previously demonstrated that intrathecal (i.t.) administration of prostaglandin (PG) E(2) and PGF(2 alpha) induced touch-evoked pain (allodynia) through the glutamatergic system by different mechanisms. In the present study, we characterized glutamate receptor subtypes and glutamate transporters involved in induction and maintenance of PGE(2)- and PGF(2 alpha)-evoked allodynia. In addition to PGE(2) and PGF(2 alpha), N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not kainate, induced allodynia. PGE(2)- and NMDA-induced allodynia were observed in NMDA receptor epsilon 4 (NR2D) subunit knockout (GluR epsilon 4(-/-)) mice, but not in epsilon 1 (NR2A) subunit knockout (GluR epsilon 1(-/-)) mice. Conversely, PGF(2 alpha)- and AMPA-induced allodynia were observed in GluR epsilon 1(-/-) mice, but not in GluR epsilon 4(-/-) mice. The induction of allodynia by PGE(2) and NMDA was abolished by the NMDA receptor epsilon 2 (NR2B) antagonist CP-101,606 and neonatal capsaicin treatment. PGF(2 alpha)- and AMPA-induced allodynia were not affected by CP-101,606 and by neonatal capsaicin treatment. On the other hand, the glutamate transporter blocker DL-threo-beta-benzyloxyaspartate (DL-TBOA) blocked all the allodynia induced by PGE(2), PGF(2 alpha), NMDA, and AMPA. These results demonstrate that there are two pathways for induction of allodynia mediated by the glutamatergic system and suggest that the glutamate transporter is essential for the induction and maintenance of allodynia.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Amino Acid Transport System X-AG; Animals; Animals, Newborn; Aspartic Acid; ATP-Binding Cassette Transporters; Capsaicin; Dinoprost; Dinoprostone; Excitatory Amino Acid Agonists; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; N-Methylaspartate; Pain; Pain Measurement; Physical Stimulation; Posterior Horn Cells; Receptors, Glutamate; Synapses; Synaptic Transmission; Touch

Although intradermal injection of capsaicin produces acute pain and secondary hyperalgesia, long-term topical application of capsaicin cream has been used as a medication for pain relief in various pain conditions. We previously reported that intrathecal administration of prostaglandin (PG) E(2) and PGF(2alpha) into mice induced touch-evoked pain (allodynia) through capsaicin-sensitive and capsaicin-insensitive afferent fibers, respectively. To clarify the mechanism of an analgesic effect by capsaicin cream, here we applied it to the tail and hind paws of mice and investigated its effects on PGE(2)- and PGF(2alpha)-induced allodynia. Twenty-four-hour pretreatment of mice with 0.025% or 0.05% capsaicin cream markedly alleviated allodynia induced by PGE(2), but not by PGF(2alpha). These results suggest that the topical application of capsaicin cream modulates capsaicin-sensitive afferents and ameliorates allodynia evoked by PGE(2) at the spinal level.. Topical application of capsaicin cream alleviates touch-evoked pain induced by the intrathecal administration of prostaglandin E(2). This study may provide a rationale for the use of capsaicin cream as a therapeutic drug for pain relief.

Topics: Animals; Capsaicin; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Male; Mice; Nerve Fibers; Ointments; Pain; Reaction Time; Receptors, N-Methyl-D-Aspartate

Muscle pains with or without CK-elevation are among the most frequently observed side-effects in patients with hyperlipoproteinemia on various statins. The pathophysiological background, however, remains obscure.. We examined isoprostane 8-epi-PGF2alpha, a marker of in-vivo oxidation injury, in plasma, serum and urine in these patients at baseline, when muscle problems manifested and different time intervals after withdrawing the respective statin. A healthy control group and a group of untreated patients with hyperlipoproteinemia were run as controls.. The majority of patients with muscular side-effects show elevated 8-epi-PGF2alpha in plasma and urine, whereas serum values were elevated only to a lesser extent. Stopping statin therapy or successfully changing to another member of this family of compounds resulted in a normalization of the values in all patients.. These findings indicate a significant involvement of oxidative injury in the muscular side-effects of statins in patients suffering from hyperlipoproteinemia.

Topics: Adult; Aged; Biomarkers; Creatine Kinase; Dinoprost; F2-Isoprostanes; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemias; Male; Middle Aged; Muscle, Skeletal; Oxidation-Reduction; Oxidative Stress; Pain; Vasoconstrictor Agents

Isoprostanes are a novel class of eicosanoids primarily formed by peroxidation of arachidonic acid. Because of their potential as inflammatory and/or hyperalgesic agents whose formation is largely independent of cyclooxygenases, we examined whether 8-iso prostaglandin E(2) (8-iso PGE(2)) or 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)) reduces mechanical and thermal withdrawal threshold in rats, and whether they sensitize rat sensory neurons. Injection of 1 microg of 8-iso PGE(2) (in 2.5 microl) into the hindpaw of rats significantly reduced mechanical and thermal withdrawal thresholds, whereas 1 microg of 8-iso PGF(2alpha) elicited a transient decrease in only the mechanical withdrawal threshold. Both isoprostanes enhanced the firing of C-nociceptors in a concentration-dependent manner when injected into peripheral receptive fields. Exposing sensory neurons grown in culture to 1 microM 8-iso PGE(2) or 8-iso PGF(2alpha) augmented the number of action potentials elicited by a ramp of depolarizing current. In contrast, 8-iso PGE(2) but not 8-iso PGF(2alpha) enhanced the release of substance P- and calcitonin gene-related peptide-like immunoreactivity from isolated sensory neurons. Ten micromolar 8-iso PGE(2) stimulated peptide release directly, whereas treatment with 1 microM 8-iso PGE(2) augmented the release evoked by either bradykinin or capsaicin. Pretreating neuronal cultures with the nonsteroidal anti-inflammatory drug ketorolac did not alter the sensitizing action of 8-iso PGE(2) on peptide release, suggesting that this action of the isoprostane was not secondary to the production of prostaglandins via the cyclooxygenase pathway. These data support the notion that isoprostanes are an important class of inflammatory mediators that augment nociception.

Topics: Action Potentials; Animals; Calcitonin Gene-Related Peptide; Cells, Cultured; Cyclic AMP; Dinoprost; Dinoprostone; F2-Isoprostanes; Female; Isoprostanes; Male; Nerve Fibers; Neurons, Afferent; Pain; Prostaglandins; Rats; Rats, Sprague-Dawley; Reaction Time; Substance P

Rhizoma Cimicifugae (RC) has been used traditionally to treat pain and inflammation in Korea. The present study was conducted to gain insights into the mechanism of action regarding analgesic and antiinflammatory activities of RC extracts. RC was first extracted with methanol. The methanol extract (A) was fractionated to an ether-soluble fraction (B) and a water-soluble fraction (C). Fraction C was fractionated to a butanol-soluble fraction (D) and a water-soluble fraction (E). Each fraction (100 mg/kg, i.p.) was tested for analgesic and antiinflammatory activities. Administration of fractions A and D caused dramatic analgesic effects based on acetic acid writhing and tail-flick assays. However, fraction E had an analgesic effect only based on the acetic acid writhing assay. Fractions A, D and E exerted antiinflammatory effects on the rat paw oedema assay. The fractions A, D, E had an inhibitory action on the bradykinin/histamine-mediated contractions of guinea-pig ileum. In addition, fractions A, D and E had the ability to inhibit the production of LPS-induced 6-keto-PGF1alpha production in macrophage cultures. Taken together, these results provide scientific evidence that RC extracts exert analgesic and antiinflammatory effects by inhibiting bradykinin/histamine mediated actions and inhibiting 6-keto-PGF1alpha induction.

Topics: Animals; Bradykinin; Dinoprost; Enzyme-Linked Immunosorbent Assay; Guinea Pigs; Histamine; Ileum; Inflammation; Korea; Macrophages; Male; Mice; Mice, Inbred ICR; Muscle Contraction; Pain; Phytotherapy; Plant Extracts; Plants, Medicinal; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley

Prostaglandin (PG) D2 is the most abundant prostanoid produced in the central nervous system of mammals and has been implicated in the modulation of neural functions such as sleep induction, nociception, regulation of body temperature, and odor responses. We generated gene-knockout mice for lipocalin-type PGD2 synthase (L-PGDS) and found that the intrathecal administration of PGE2, an endogenous pain-producing substance, failed to elicit allodynia (touch-evoked pain), which is one typical phenomenon of neuropathic pain, whereas it evoked thermal hyperalgesia, in L-PGDS-/- mice. We also found that the allodynic response induced by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline was selectively abolished in the L-PGDS-/- mice, among excitatory and inhibitory agents that induced allodynia in wild-type mice. Interestingly, simultaneous injection of a femtogram amount of PGD2 with PGE2 or bicuculline induced allodynia in L-PGDS-/- mice to the same extent as in wild-type mice. The PGE2- or bicuculline-evoked allodynia in wild-type and in PGD2-supplemented L-PGDS-/- mice was blocked by a PGD2 receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD2 is essential for both PGE2- and bicuculline-induced allodynia.

Topics: Anesthesia; Animals; Bicuculline; Central Nervous System; Dinoprost; Dinoprostone; GABA Antagonists; Gene Targeting; Hydantoins; Hyperalgesia; Immunohistochemistry; Intramolecular Oxidoreductases; Lipocalins; Mice; Mice, Knockout; Molecular Sequence Data; Pain; Prostaglandin D2; Receptors, Prostaglandin

The duration of the somatostatin-, bradykinin- or prostaglandin F2alpha-induced nociceptive response was significantly less in diabetic mice than in non-diabetic mice. Subcutaneous injection of 7-benzylidenenaltrexone (0.1, 0.3 and 1 mg/kg), an antagonist of delta1-opioid receptors, had no significant effect on either somatostatin-, bradykinin- or prostaglandin F2alpha-induced nociceptive responses in non-diabetic mice. 7-Benzylidenenaltrexone (0.1 and 0.3 mg/kg, s.c.) also had no significant effect on somatostatin- or prostaglandin F2alpha-induced nociceptive responses in diabetic mice. However, the bradykinin-induced nociceptive response in diabetic mice was dose-dependently and significantly increased when 7-benzylidenenaltrexone (0.1, 0.3 and 1 mg/kg, s.c.) was injected 10 min before the injection of bradykinin. These results suggest that a spinal delta1-opioid receptor-mediated endogenous antinociceptive system may inhibit the bradykinin-mediated nociceptive responses in the second phase of the formalin-induced nociceptive response in diabetic mice.

Topics: Animals; Benzylidene Compounds; Bradykinin; Diabetes Mellitus, Experimental; Dinoprost; Dose-Response Relationship, Drug; Formaldehyde; Injections, Subcutaneous; Male; Mice; Mice, Inbred ICR; Naltrexone; Narcotic Antagonists; Pain; Receptors, Opioid, delta; Somatostatin

Anatomical data indicate that the rat uterine horn is innervated primarily by afferent fibers in the hypogastric nerves, suggesting that hypogastric neurectomy, but not pelvic or pudendal neurectomy, should eliminate behavioral responses to uterine horn stimulation. To test this hypothesis, detection and escape responses of rats to different volumes of uterine horn distention (via an indwelling intrauterine balloon) were compared before and after bilateral hypogastric (n = 9), sham-hypogastric (n = 3), pelvic (n = 3), or pudendal (n = 2) neurectomies. As predicted, sham-hypogastric, pelvic, and pudendal neurectomies had no effect on the rats' responses. However, although hypogastric neurectomy completely eliminated responses in five rats whose postmortem evaluation revealed no signs that the uterine balloons had evoked any pelvic pathophysiology, the neurectomy had no effect on the responses of an additional four rats. Postmortem evaluation of these rats revealed gross signs of severe pathology in the vicinity of the balloon in two rats, and evidence that the balloon had shifted caudally so that it was stimulating the cervix rather than the uterine horn in a third. In the fourth rat, pathophysiology had been deliberately induced by the prior implantation of a small pellet that released approximately 1 microg/day of prostaglandin PF2alpha over the uterine horn. Similar findings have been reported in clinical studies on the efficacy of hypogastric ('presacral') neurectomy for dysmenorrhea. Together, the findings support the hypothesis that the major source of afferent innervation of the uterine horn in healthy rats and women is the hypogastric nerve but that the situation changes under conditions of pelvic pathology. Such changes could include additional activation of afferent fibers in nerves that supply other pelvic organs, activation by the uterine pathophysiology of latent uterine innervation from afferent fibers in the pelvic, vagus or ovarian plexus nerves, or some form of central sensitization.

Topics: Animals; Catheterization; Conditioning, Operant; Dinoprost; Drug Implants; Escape Reaction; Female; Hypogastric Plexus; Oxytocics; Pain; Pain Measurement; Rats; Uterus

We previously reported that intrathecal administration of prostaglandin (PG) D2 and PGE2 to conscious mice induced hyperalgesia (assessed by a hot-plate test) and that intrathecal administration of PGE2 and PGF2 alpha induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli. In the present study, we examined the relationships of pain responses among PGD2, PGE2 and PGF2 alpha, PGF2 alpha additively augmented the allodynia evoked by a submaximal dose (1 ng/mouse) of PGE2. On the other hand, PGD2 dose-dependently blocked the allodynia induced by a maximal dose (10 ng/mouse) of PGE2, with an IC50 of 93.2 pg/mouse, but did not affect the PGE2 (10 ng)-induced hyperalgesia at doses up to 10 ng. BW 245C, an agonist for PGD2 receptors (DP receptors), but not another DP receptor agonist (ZK 110841) blocked the allodynia similarly. The blockade of PGE2-induced allodynia by 10 ng of PGD2 was reversed by the potent and selective DP receptor antagonist BW A868C, in a dose-dependent manner. Intrathecal administration of BW A868C induced allodynia by itself over a wide range, from 10 pg to 100 ng. and the allodynia induced by 100 ng of BW A868C was dose-dependently antagonized by PGD2. These results demonstrate that PGD2 blocked the PGE2-evoked allodynia through DP receptors in the spinal cord, and they imply that endogenous PGD2 may play an inhibitory role in the appearance of allodynia under physiological conditions.

Topics: Adrenergic Agonists; Animals; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Glycine; Hydantoins; Male; Mice; N-Methylaspartate; Pain; Prostaglandin D2; Spinal Cord; Wakefulness

We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) E2 or PGF2 alpha in conscious mice induced allodynia through a pathway that includes the glutamate receptor system. Allodynia induced by PGE2 and PGF2 alpha was blocked by antagonists for NMDA and metabotropic glutamate receptor subtypes, respectively. In the present study, we examined the possibility for the involvement of nitric oxide (NO) in the PG-evoked allodynia. Allodynia was assessed once every 5 min by light stroking of the flank of mice with a paintbrush. Intrathecal administration of L-arginine, a substrate of nitric oxide synthase (NOS), in conscious mice resulted in allodynia. Dose dependency of L-arginine for allodynia showed a bell-shaped pattern (1-10 micrograms/mouse). The maximal allodynic effect was observed with 5.0 micrograms at 10-15 min after i.t. injection, similar in time course and magnitude to that induced by L-glutamate. L-Arginine-induced allodynia was dose-dependently reduced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) and the soluble guanylate cyclase inhibitor methylene blue with IC50 values of 7.68 and 8.70 pg/mouse, respectively. PGE2-induced allodynia was also dose-dependently inhibited by L-NAME and methylene blue with IC50 values of 94.7 and 74.9 pg/mouse. PGF2 alpha-induced allodynia was inhibited by methylene blue with an IC50 value of 40.6 pg/mouse, but not by L-NAME at doses up to 1.0 ng.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Arginine; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Injections, Spinal; Male; Methylene Blue; Mice; Mice, Inbred Strains; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pain; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

In order to investigate the involvement of glutamate receptor systems in allodynia induced by prostaglandin (PG) E2 or F2 alpha, we co-administered antagonists for N-methyl-D-aspartate (NMDA), non-NMDA, or metabotropic glutamate receptors intrathecally with PGE2 or PGF2 alpha and examined their effects on the allodynia evoked in conscious mice by non-noxious brushing of the flanks. MK-801, a non-competitive NMDA receptor channel blocker, and D-AP-5, a selective NMDA receptor antagonist, dose-dependently blocked PGE2-induced allodynia with an IC50 of 1.60 and 0.52 microgram/mouse, respectively. A glycine binding-site antagonist for the NMDA receptor, 7-Cl-KYNA, did not influence it. None of these NMDA receptor antagonists inhibited PGF2 alpha-evoked allodynia. Non-NMDA receptor antagonists GAMS and CNQX inhibited both PGE2- and PGF2 alpha-induced allodynia. On the other hand, L-AP-3 and L-AP-4, putative metabotropic glutamate receptor antagonists, dose-dependently antagonized the allodynia induced by PGF2 alpha with an IC50 of 0.92 and 3.26 ng/mouse, respectively, but not that induced by PGE2. Intrathecal administration of L-glutamate produced allodynia over a wide range of low doses from 0.1 pg to 0.1 microgram/mouse, and the maximal effect was observed at 1 ng. Similar to allodynia induced by prostaglandins, the response lasted over a 50-min experimental period. These results demonstrate that both PGE2- and PGF2 alpha-evoked allodynia are mediated through a pathway that includes the glutamate receptor system but that subtypes of glutamate receptors involved and sites of action in the spinal cord may be different between them.

Topics: Animals; Dinoprost; Dinoprostone; Glutamates; Glutamic Acid; Injections, Spinal; Mice; Neurotransmitter Agents; Pain; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Synaptic Transmission

CI-986 is a potent inhibitor of 5-lipoxygenase and cyclooxygenase pathway product biosynthesis from rat basophilic leukemia (RBL) cells. Because metabolites from these pathways have proinflammatory properties, CI-986 was evaluated in several acute and chronic models of inflammation and hyperalgesia. The compound inhibited swelling in the carrageenan footpad edema, Mycobacterium foot-pad edema and adjuvant arthritis models of inflammation with ID40 values of 1.0, 7.7., and 7.2 mg/kg, respectively. It was roughly equivalent in potency to the standard selective cyclooxygenase inhibitor, naproxen (ID40 = 0.7, 6.3, and 3.8 mg/kg, respectively). CI-986 was also evaluated in the acetic acid induced writhing hyperalgesia assay (ID50 = 0.23 mg/kg) and was approximately equipotent with indomethacin (ID50 = 0.87 mg/kg). Although the effects of CI-986 were similar to those of standard nonsteroidal antiinflammatory drugs (NSAIDs) in the inflammation models, its gastrointestinal profile was unique. CI-986 caused no gastrointestinal irritation at doses up to 200 mg/kg in acute and chronic studies. In contrast, standard NSAIDs caused ulcers at doses of 3.7-37 mg/kg after a single dose. Moreover, CI-986 inhibited the release of LTC4 and PGE2 by gastric mucosa and reduced mucosal and vascular damage induced by oral administration of absolute ethanol to rats. These results indicate that CI-986 is a potent nonulcerogenic antiinflammatory agent with novel pharmacologic properties.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arthritis, Experimental; Cyclooxygenase Inhibitors; Dinoprost; Disease Models, Animal; Ethanol; Female; Gastritis; Inflammation; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mice; Pain; Rats; Rats, Wistar; Thiadiazoles; Tumor Cells, Cultured

To determine the analgesic efficacy of the opioid agonist-antagonist Nubain during midtrimester therapeutic terminations with intra-amniotic PGF2 alpha or i.m. administration of the PGE2 derivative sulprostone.. Following osmotic predilatation with laminaria tents patients were given as a premedication 10 mg Valium, 10 mg Nubain and 0.5 mg atropine i.m. prior to prostaglandin treatment, and sequential doses of Nubain during the uterine contractility period. Patients indicated their own perception of uterine pain on a differential graphic rating scale, and the attending physician also evaluated patients' discomfort on a 5-grade scale.. In 55% of the cases patients experienced only 'mild' or 'moderate' pain. The mean induction-to-abortion interval was short (11.6 +/- 1.3 h). The well known gastrointestinal side-effects of the prostaglandins were avoided.. Nubain proved effective in stabilizing patients' condition during intra-amniotic instillation of prostaglandin, effectively relieved uterine pain during the myometrial contractility period, prevented the occurrence of prostaglandin-related side-effects, and provided simple and good anesthesia during instrumental removal of the already detached but retained placenta.

Topics: Abortion, Therapeutic; Adult; Dinoprost; Female; Humans; Injections, Intramuscular; Nalbuphine; Pain; Pain Measurement; Pregnancy; Pregnancy Trimester, Second; Premedication; Uterus

The intrathecal administration of prostaglandin F2 alpha to conscious mice resulted in spontaneous agitation and touch-evoked agitation (allodynia) in the animals. The maximum allodynia induced by prostaglandin F2 alpha was observed at 10-15 min after intrathecal injection, and the response did not disappear by 120 min. Prostaglandin F2 alpha produced allodynia over a wide range of dosage from 0.1 pg to 2.5 micrograms/mouse. Dose dependency of prostaglandin F2 alpha for allodynia showed a skewed bell-shaped pattern, and the maximal allodynic effect was observed at 1.0 microgram. This allodynia was dose-dependently relieved by alpha 1-adrenergic (methoxamine), alpha 2-adrenergic (clonidine), and A1-adenosine (RPIA) agonists. Clonidine was 1.5 orders of magnitude more potent than methoxamine in blocking prostaglandin F2 alpha-induced allodynia. The blockade by clonidine was dose-dependently reversed by the alpha 2-adrenergic antagonist yohimbine but not by the alpha 1-adrenergic antagonist prazosin. These results demonstrate that prostaglandin F2 alpha administered intrathecally induces allodynia in conscious mice and that the allodynia involves the alpha 2-adrenergic and A1-adenosine systems. Because this allodynia has a clear resemblance to the characteristics of chronic pain in patients with causalgia and reflex sympathetic dystrophy, prostaglandin F2 alpha may be involved in allodynia observed with these disorders.

Topics: Adenosine; Animals; Behavior, Animal; Dinoprost; Dose-Response Relationship, Drug; Injections, Spinal; Male; Mice; Mice, Inbred Strains; Pain; Reaction Time; Sympathomimetics

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

An experimental model of acute painful trauma under electroacupuncture (EAP) protection was established. During the first 15 minutes of acute pain and EAP F2 alpha-prostaglandin, serotonin, and histamine concentrations decreased in arterial blood corresponding to increased concentrations of endogenous opiates in cerebrospinal fluid. In 30 minutes of acute pain and EAP the concentration of opiates (methionine-enkephaline, leucine-enkephaline) begins to decrease, but F2 alpha-prostaglandine, serotonin and histamine content increases significantly. The concentration of cyclic nucleotides changes significantly at investigation stages. However, they are not significant in EAP mechanism, but they are modulators of endogenous opiate effects and implement interaction between them and prostaglandines. We consider that the analgetic effect caused by EAP under acute surgical trauma is connected not only with endogenous opiate system activation, but with synthesis suppression of "pain substances".

Topics: Animals; Dinoprost; Dogs; Electroacupuncture; Enkephalin, Leucine; Enkephalin, Methionine; Histamine; Pain; Serotonin

Intrathecal administration of PGE2 and PGF2 alpha and intradermal administration of PGE2 but not PGF2 alpha, in low doses, produce hyperalgesia as measured by the Randall-Selitto paw-withdrawal test. Indomethacin (2 mg/kg, i.p.) prevented intrathecal PGF2 alpha, but not PGE2-induced hyperalgesia. We propose that the central nociceptive effects of PGF2 alpha are mediated, indirectly, by effecting the cyclo-oxygenation of arachidonic acid in the central nervous system.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Central Nervous System; Dinoprost; Dinoprostone; Indomethacin; Injections, Intraperitoneal; Injections, Spinal; Male; Pain; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Rats

Hyperalgesic actions in mice of intracerebroventricularly (i.c.v.) administered arachidonic acid, prostaglandin (PG) E2, PG F2 alpha and PG D2 were studied. For the analgesic assay, the mouse tail pressure method was employed. The i.c.v. administration of arachidonic acid (0.01-100 micrograms/mouse), PG E2 (0.01-100 ng/mouse), PG F2 alpha (0.1-1000 ng/mouse) and PG D2 (0.1-1000 ng/mouse) decreased the pain threshold in a dose dependent manner. The doses that produced the maximal decrease in pain threshold for arachidonic acid, PG E2, PG F2 alpha and PG D2 were 10 micrograms/mouse, 10 ng/mouse, 100 ng/mouse and 100 ng/mouse, respectively. Acidic nonsteroidal antiinflammatory drugs (NSAIDs) produced much more potent analgesic effects in arachidonic acid-induced hyperalgesic mice than in normal mice and in PG E2-, PG F2 alpha- and PG D2-induced hyperalgesic mice, but nonacidic NSAIDs and morphine produced the same analgesic effect in both hyperalgesic and normal mice. Linoleic acid, linolenic acid and gamma-linolenic acid induced weak hyperalgesia, but this unsaturated fatty acids-induced hyperalgesia was not affected by indomethacin (2 mg/kg, p.o.). These findings indicate that the arachidonic acid and its metabolites were related to mediation or modulation of central pain pathways and that the central nervous system may be partially involved in the action of acidic NSAIDs.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arachidonic Acids; Dinoprost; Dinoprostone; Fatty Acids, Unsaturated; Injections, Intraventricular; Male; Mice; Pain; Prostaglandin Antagonists; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Sensory Thresholds

The present study compares two methods of local application of prostaglandins prior to surgical abortion in the first trimester. Fifty patients were treated with a vaginal tablet of Gemeprost (E1 analogue); 50 others by the intra-cervical application of PGF2 alpha gel. Gemeprost was found to be superior to the PGF2 alpha gel. Several hypotheses are formulated to explain this observation. The side effects of the two methods are compared and discussed.

Topics: Abortion, Induced; Administration, Topical; Adult; Alprostadil; Cervix Uteri; Dilatation; Dinoprost; Female; Gels; Humans; Pain; Parity; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Prostaglandins F; Tablets

The effect of intracisternal administration of three major prostaglandins on nociceptive responses was evaluated in mice. Prostaglandin D2 had biphasic effects on pain thresholds (hot plate and acetic acid writhing tests) when given in a dosage range of 5 ng to 5 micrograms per mouse. Lower doses of prostaglandin D2 (less than or equal to 15 ng) increased the sensitivity to pain stimulation. Higher doses (greater than or equal to 50 ng) caused hypoalgesia, which was completely blocked by intracisternal injection of 500 pg of naloxone. Prostaglandin E2 (5 ng-5 micrograms) also had a biphasic effect on pain thresholds, similar to the effect of prostaglandin D2. However, the hypoalgesia caused by a higher dose of prostaglandin E2 (5 micrograms) was not blocked at all by naloxone doses of up to 500 ng. Prostaglandin F2 alpha had little effect on pain thresholds. These results indicate that each prostaglandin has a specific effect on the modulation of nociception.

Topics: Animals; Cisterna Magna; Dinoprost; Dinoprostone; Injections; Male; Mice; Nociceptors; Pain; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Reaction Time; Time Factors

Prostacyclin was infused into the uterus of non-pregnant women either during early menstruation or in the secretory phase of the cycle. A dose of 5 micrograms/min produced little systemic effect and caused a significant decrease in uterine activity on Days 1 and 2 of the menses whereas 0.5 microgram/min did not. However, when dysmenorrhoeic pain and increased uterine activity were produced by infusion of PGF2 alpha during the secretory phase, PGI2 neither decreased the activity nor the pain. This indicates that PGI2 does not cause uterine relaxation by blocking the action of PGF2 alpha.

Topics: Adult; Dinoprost; Epoprostenol; Female; Humans; Infusions, Parenteral; Menstruation; Muscle Contraction; Muscle, Smooth; Pain; Prostaglandins F; Uterus

Hyperalgesic actions in rats of intracerebroventricularly (i.c.v.) administered arachidonic acid, prostaglandin (PG) E2 and PG F2 alpha were studied. For the analgesic assay, vocalization induced by repetitive electrical stimulation was employed. Administered i.c.v., arachidonic acid (0.1-30 micrograms/rat), PG E2 (0.001-0.3 micrograms/rat) and PG F2 alpha (0.01-3 micrograms/rat) potentiated the vocalization, in a dose-dependent manner. The maximal potentiating doses of arachidonic acid, PG E2 and PG F2 alpha were 10 micrograms/rat, 0.1 microgram/rat and 1 microgram/rat, respectively. Indomethacin and diclofenac produced much more potent analgesic effects in arachidonic acid-induced hyperalgesic rats than in normal rats and in PG E2- and PG F2 alpha-induced hyperalgesic rats, but aminopyrine, acetaminophen and morphine produced the same analgesic effect in both hyperalgesic and normal rats. Linoleic acid, linolenic acid and gamma-linolenic acid also induced a weak hyperalgesia, whereas indomethacin (4 mg/kg) failed to attenuate the vocalization in these unsaturated fatty acids-induced hyperalgesic rats. These findings indicate that the hyperalgesic actions of arachidonic acid and its metabolites are related to mediation or modulation of the central pain pathways, and the pain-relieving properties of acidic nonsteroidal antiinflammatory drugs (NSAIDs) may be, at least in part, involved in central site.

Topics: alpha-Linolenic Acid; Analgesics; Animals; Arachidonic Acid; Arachidonic Acids; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; gamma-Linolenic Acid; Injections, Intraventricular; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Pain; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Time Factors

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

Both vasopressin and PGF2 alpha are effective uterine stimulants in the non-pregnant human uterus, especially around the onset of menstruation. In order to clarify the relationship of these hormones to menstrual pain, plasma concentrations of vasopressin and two prostaglandin metabolites (15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites) were measured in serial blood samples taken premenstrually and during menstruation. Five women with premenstrual pain gave 7-9 blood samples at intervals of 30 minutes on the day preceding the onset of menstruation. From 5 women with severe primary dysmenorrhea a corresponding series of blood samples were taken during the first day of menstruation. Two groups of 5 women with no symptoms served as controls, either premenstrually or during menstruation. In the women with premenstrual pain the vasopressin concentrations were significantly higher than in the corresponding control group. Even higher and markedly fluctuating vasopressin levels were found in the women with dysmenorrhea who, in general, had more intense pain than the women with premenstrual symptoms. In the group with dysmenorrhea there was also a significant rise in plasma concentration of the PG metabolites. No such increase was seen in the group with premenstrual pain. It is concluded that the pathophysiology of premenstrual pain could imply increased vasopressin secretion. The more severe pain in primary dysmenorrhea seems to be the result of a combined effect of vasopressin and PGF2 alpha.

Topics: Adolescent; Adult; Dinoprost; Dysmenorrhea; Estradiol; Female; Humans; Osmolar Concentration; Pain; Premenstrual Syndrome; Progesterone; Prostaglandins F; Vasopressins